J Neurosurg 71:754-764, 1989

Experimental missile wound to the brain

MICHAEL E. CAREY, M.D., GURCIIARAN S. SARNA, PH.D., J. BRYAN FARRELL, B.S., AND
LEO T. HAPPEL, PH.D.
Department ( f Neurosurgery, Louisiana State University Medical Center, New Orleans, Louisiana

u,- Among civilians in the United States, 33,000 gunshot wound deaths occur each year; probably half0f
these involve the head. In combat, head wounds account for approximately half of the immediate mortality
when death can be attributed to a single wound. No significant reduction in the neurosurgical mortality
associated with these wounds has occurred between World War II and the Vietnam conflict, and verylittle
research into missile wounds of the brain has been undertaken. An experimental model has been devel01N
in the anesthetized cat whereby a ballistic injury to the brain may be painlessly reproduced in order thatthe
pathophysiological effects of brain wounding may be studied and better treatments may be designed to lower
the mortality and morbidity rates associated with gunshot wounds.
Prominent among physiological effects observed in this model was respiratory arrest even though the missile
did not injure the brain stem directly. The incidence of prolonged respiratory arrest increased with increasing
missile energy, but arrest was often reversible provided respiratory support was given. It is possible that humans
who receive a brain wound die from missile-induced apnea instead of brain damage per se. The rn0rtalityrate
in humans with brain wounding might be reduced by prompt respiratory support. Brain woundingw~
associated with persistently increased intracranial pressure and reduced cerebral perfusion pressure not entirely
attributable to intracranial bleeding. The magnitude of these derangements appeared to be missile energy.
dependent and approached dangerous levels in higher-energy wounds.
All wounded cats exhibited postwounding increases in blood glucose concentrations consistent witha
generalized stress reaction. A transient rise in hematocrit also occurred immediately after wounding. Bothof
these phenomena could prove deleterious to optimal brain function after injury.

KEY WORDS penetrating head injury brain injury missile wound . apnea ’
intracranial pressure emergency care

I
N combat, the head receives about 20% of all "hits"
and head w o u n d s a c c o u n t for approximately half
o f all single missile deaths? The most comprehen-
sive data on the surgical treatment o f missile w o u n d s
to the brain c o m e from neurosurgical series reported
f r o m various wars o f the 20th century. Review o f these
neurosurgical statistics reveals no significant reduction
in the neurosurgical mortality rate from w o u n d s in-
flicted in World War II through the V i e t n a m experi-
ence: during World W a r II, the neurosurgical mortality
rate for United States A r m y soldiers in Europe was 14%
while in the Korea and Vietnam conflicts it was 10%
to 12%. 4"5’19"35’36
A m o n g civilians in the United States, approximately
33,000 deaths each year are caused by bullet wounds. 24
A s s u m i n g that no difference exists between civilian and
military w o u n d s in their potential lethality to specific
b o d y regions, one m a y infer that missile w o u n d s to the
brain a c c o u n t for approximately 16,500 civilian dean
from g u n s h o t w o u n d s each year in the United States
Despite the serious problem o f brain wounds for mili.
tary personnel and for civilians, very little experi-
mental research into brain wounding has been under-
taken.6 11,16,30,48
We have developed an experimental model to real-
istically simulate a missile w o u n d to the brain which
would not necessarily result in death. It is hoped thata
better knowledge o f the pathophysiology of brain
w o u n d i n g m a y lead to correction of specific derange-
ments contributing to mortality and morbidity. The
present c o m m u n i c a t i o n gives technical details of the
laboratory gun, delineates the "standard brain wound,"
provides an analysis o f acute breathing abnormaliti~
seen with brain w o u n d i n g in this model, and presents
some central and peripheral pathophysiological effects
caused by a nonfatal missile w o u n d to the brain.

754 J. Neurosurg. / Volume 71/November, 1989

 Experimental missile wound to brain
Materials and M e t h o d s
Laboratory Gun
The laboratory gun* consists of a precision-made
~eeltube seated inside a 69-cm hollow steel bar. The
insidediameter of the steel tube just accommodates the
testmissile, a 2.0-ram 31.7-rag steel sphere. The breech-
loaded barrel is coupled to a solenoid valve which
controls the release of pressurized helium propellant.
Missile velocity is a function of helium pressure. The
triggering mechanism provides a direct current power
sourcesupplying a solenoid valve. The time required
forthe missile to pass between two electronic break
~reens set exactly 50 cm apart is determined by an
electronic time base. Missile energy (E, in joules) is
calculated by: E = 1/2 m v 2, where m represents mass
(inkg) and v represents velocity (in m/see).
SurgicalProcedures
Unselected, unfasted mongrel cats, each weighing 3
to 5 kg, were used in this study. After induction of
pent0barbital anesthesia (40 mg/kg intraperitoneally),
unilateral or bilateral groin incisions were made for
femoralartery or vein cannulations. One femoral arte-
rialline was connected to a transducer physiograph for
bloodpressure recording while the other femoral artery
catheter was used for blood sampling as needed.t All
groinincisions were closed. An endotracheal tube was
thenplaced and end-expiratory CO2 was continuously
~c0rded.:~ Each cat was placed prone in a stereotactic
frame80 cm from the muzzle of the helium gun.w In
order to prevent the missile from ricocheting off the
slopedanterior wall of the cat’s frontal sinus, the ante-
ri0rwall of the right frontal sinus was removed. The
posteriorsinus wall, which remained intact, was vertical
tothe missile trajectory and was readily penetrated by
thewounding sphere.
Experimental Procedures
In conducting the research described in this report,
the investigators adhered to the "Guide for the Care
and Use of Laboratory Animals," prepared by the
Committeeon Care and Use of Laboratory Animals of
theInstitute of Laboratory Animal Resources, National
Research Council. At the start of each experiment
baselinerecordings were made of physiological variables
including mean arterial blood pressure (MABP), end-
tidal CO2, and respiratory frequency. Arterial blood
gasanalyses and intracranial pressure (ICP) measure-
mentswere made in selected experiments. After check-
*Laboratory gun designed and constructed by Mr. Robert
Carpenter, formerly with the Edgewood Arsenal, Aberdeen,
Maryland.
tTransducer, Model P1000B, and physiograph, Model
DMP4A, manufactured by Narco Bio-Systems, Houston,
Texas.
End-tidal CO, monitor, Model IL-200, manufactured by
Instrumentation Laboratory, Lexington, Massachusetts.
wStereolactic frame manufactured by David Kopf Instru-
ments,Tujunga, California.
J.Neurosurg. / Volume 71/November, 1989
ing that a satisfactory level of anesthesia was present so
that the experimental cats would feel no pain, they
were wounded in the right cerebral hemisphere. Subse-
quently, various physiological or behavioral variables
were measured. Control cats underwent anesthesia, sur-
gery, and placement in the stereotactic frame but were
not wounded.
Results presented in this report were derived from
two series of cats. In the first series the effects of missile
wounding upon breathing were obtained from a retro-
spective analysis of 83 cats studied primarily for the
evaluation of postwounding brain edema and/or behav-
ior. These cats were wounded through a completely
intact skull. If a cat became apneic following wounding
and if spontaneous breathing did not resume within 1
minute, the animal was ventilated until spontaneous
breathing resumed, or for a m a x i m u m of 2 hours.
Return of respirations in apneic cats was evident from
the end-tidal CO2 trace. The ability to breathe sponta-
neously was also tested by the periodic brief removal
of the ventilator. In cats allowed to recover from anes-
thesia and wounding, local antibiotic ointment and
topical anesthetic were applied to all sutured skin in-
cisions. They were given penicillin G (50,000 U in-
tramuscularly), carefully nursed, and observed in the
animal care facility until they had fully recovered. If
necessary, hydration was supplied by normal saline
solution given intraperitoneally for the first few days
after wounding. During the recovery period no cat
appeared in any pain. At the appropriate times the cats
were sacrificed with intravenous pentobarbital and ex-
sanguinated, and their brains were removed.
In the second series of 20 cats the effect of missile
wounding upon several physiological variables, includ-
ing ICP, was determined after an epidural pressure
balloon had been inserted through a left parietal crani-
ectomy prior to wounding. II The craniectomy was then
sealed with methyl methacrylate. Four groups of five
cats each (both sexes) were used in this series of exper-
iments. G r o u p 1 consisted of unwounded cats (control
group), while cats in Groups 2 through 4 were wounded
by a missile having a mean energy of 0.90, 1.40, or 2.50
J. In all groups MABP, ICP, cerebral perfusion pressure
(CPP; CPP = MABP - ICP), heart rate, respiratory
frequency, and end-tidal CO_, were monitored contin-
uously for 6~ hours. Arterial blood was sampled (1.5 ml
each) before injury, at 1, 3, 5, 10, 20, 30, and 60
minutes, and at 2, 3, 4, 5, and 6 hours after wounding.
Blood samples were analyzed for pCO~, pO2, pH, blood
glucose concentration, and hematocrit.* All of the cats
were painlessly sacrificed by intravenous pentobarbital
at the end of the experimental period.
I] Epidural pressure balloon, Model ICT/b, manufactured
by MMI-Gaeltec, Hackensack, New Jersey.
* Blood gas and pH analyzer manufactured by Instrumen-
tation Laboratory, Lexington, Massachusetts; Dextrometer,
Model 5570, manufactured by Ames Division, Miles Labo-
ratory, Inc., Elkhart, Indiana.
755

In this group only the data obtained during the first
hour postwounding were analyzed because these data
best demonstrated the effect of brain wounding alone
in the pentobarbital-anesthetized cat. After this time,
anesthesia lessened. All results are given as the mean +
standard deviation. The data were initially analyzed by
analysis of variance for repeated measures. Individual
comparisons were made using Student-Newman-Keuls’
test. Results were considered significant at p < 0.05.
Results
Ballistic Considerations and the Brain Wound
Missile Velocity and Energy. For any given shot
the velocity error was less than 2.5% and the energy
error less than 4.5% compared with that intended. A
missile velocity of 178 to 210 m/sec (0.50 to 0.70 J)
was required to penetrate the posterior wall of the fight
frontal sinus which is about 1 m m thick. Consistent
bone penetration was achieved with a sphere velocity
of 238 m/sec (0.90 J) and this determined the lower
ballistic limit of the model. When missile velocity was
increased to 389 m/sec (2.50 J) and the sphere was fired
through the completely intact skull into the fight cere-
bral hemisphere, the wound was fatal in two-thirds of
instances owing to immediate respiratory arrest. This
velocity and energy represented the upper ballistic limit
permissible in our model. A missile velocity of 297 m /
sec (1.4 J) produced a fatality from apnea in about 40%
of all cats. Because our interest was in the pathophysi-
ology of nonfatal brain wounds, most experiments were
carried out with missile velocities from 238 to 297 m /
see (0.90 to 1.40 J).
Assuming a skull 1 m m thick (approximately the
thickness of the posterior frontal sinus wall through
which the test missile enters), a skull strength of 100
megapascals, and a breaking strain of 1%, our test
missile loses only about 20 m/sec (0.09 J) velocity with
skull penetration. (M Iremonger, personal c o m m u n i -
cation, 1987). This small loss of velocity and energy
FIG. 1. Dorsal view of a cat’s brain showing the plane of
the missile track angling away from the brain stem. There is
little blood in the subarachnoid space.
756
M.E. Carey, etaL
from frontal bone penetration will not be considered
further in discussing wound velocities and energies in
this experimental model.
Missile Trajectory and Wound Characteristics.
The animals’ occiputs were rotated 20 ~ to the left in
the stereotactic frame. The missile invariably entered
the brain at the right frontal tip through the cruciate
sensorimotor cortex which was hemorrhagic and con-
tused from 2 to 4 m m around the missile entry site,
Tiny flakes of frontal bone were sometimes seen near
the entrance of the brain wound track. In most in-
stances after skull penetration the missile continued
into the right lateral parieto-occipital region away from
the lateral ventricle and brain stem. This trajectory
minimized as far as possible the physiological brain-
stem effects that would have been accentuated by mis-
sile impact directly over the medulla (Fig. 1).
Most missiles traversed the superior half of the right
cerebral hemisphere above and lateral to the lateral
ventricle (Fig. 2). The missile usually struck the inside
of the skull posteriorly. It might then ricochet to the
tentorium and bounce back into the brain for several
millimeters. Hence, the right occipital pole often re-
ceived more extensive damage than the fight frontal tip.
The missile track itself was filled with varying amounts
of blood ranging from very little to obvious major dots.
Some subarachnoid bleeding occurred in all cases over
the wounded hemisphere; a small amount of blood was
frequently found in the area of the brain stem and was
rarely seen over the contralateral cerebral hemisphere.
The anterior surfaces of the right cerebellum and the
right inferior colliculus lying under the tentorium were
often slightly contused.
Effects of Wounding on Breathing
Table 1 summarizes the effect of brain wounds
caused by missiles of different energies upon breathing
and the duration of brain wound-induced apnea, Ap-
a . . . . . .
I I I I I I I I I I I I
15 10 5 0 15 10 5 0 15 10 5 0
mm mm mm
FIG. 2. Drawings of coronal brain sections 14 mrn caudal
to the right frontal tip showing characteristic missile track
locations and sizes in nine cats (a to i). Only occasionallydid
missile tracks deviate from this region. The three tracksde-
picted in each drawing are shaded differently.
J. Neurosurg. / Volume 71/November, 1989
Experimental missile wound to brain
proximately the same percentage of cats in the 0.90-J
and the 2.50-J energy groups never experienced post-
wounding apnea. A m o n g all cats experiencing apnea,
however, those with milder wounds (0.90 and 1.40 J)
weremuch more likely to have shorter periods of apnea
(up to 1 minute) than were those receiving the most
severewound (2.50 J). Increasing wound energy signif-
icantly increased the likelihood of prolonged apnea of
6 minutes or longer.
Table 2 shows the effect of early respiratory support
for eats that became apneic for 6 minutes or longer.
For data analysis, animals that did not resume sponta-
neous breathing within 6 minutes were considered to
be "dead" even though they may have subsequently
recoveredventilatory function owing to respiratory sup-
port. This end-point was chosen because anesthetized
uninjured cats develop fatal cardiac failure and per-
manent loss of electroencephalographic recording if
apnea lasts longer than 5 or 6 minutes (D Torbati, D
hwasthi, ME Carey, unpublished data).
Early respiratory support was beneficial but became
lessso when brain wounds were caused by high-energy
(2.50-J) missiles. Nevertheless, t5 (60%) of 25 cats
rendered apneic for 6 minutes or longer were saved by
means of prompt respiratory support. Twenty minutes
wasthe median ventilatory support time but one animal
required 80 minutes. Fourteen of 36 cats wounded at
1.40J became apneic for 6 minutes or longer. All were
ventilated following 1 minute of postwounding respi-
rat0ry arrest, and 10 subsequently resumed spontane-
ous breathing. The beneficial effect of respiratory sup-
port in this group was highly significant (p < 0.005,
McNemar’s test). Eight of the 10 resuscitated cats from
this group lived from 24 hours to 38 months after
wounding, at which time they were sacrificed. After
resumption of spontaneous breathing, these cats were
TABLE 1
Effectof brain missile wounds upon breathing and duration of
wound-induced apnea
Missile No. of % Never % Apneic for (min):
Energy (J) Cats Apneic 0.1 to 1.0 > 1.0 to < 6.0
0.90 35 14.3 60.0 17.1
1.40 36 2.8 52.7 5.6
2.50 12 16.7 0 16.6
TABLE 2
E~cacyof respiratory supportfor apneic brain-wounded cats*
Effect of Missile Energy (J)
Respiratory Support 0.90 1.40 2.50
total apneic - 6 min ("dead") 3 14
did not resume breathing 1 4
resumed spontaneous breathing 2 10
* Valuesare number of cats,
d.Neurosurg. / Volume 71/November, 1989
behaviorally indistinguishable from cats that had never
become apneic following wounding.
Selected Physiological Effects o f Brain Wounding
Data on selected central and peripheral physiological
effects of brain wounding were obtained from the sec-
ond series of cats into which an ICP monitor had been
placed prior to wounding.
Changes in M A B P , ICP, and C P P
A m o n g the five animals in the control group, MABP
showed a significant rise from 97.0 + 10 m m Hg when
first observed to 120 _+ 15.0 m m Hg at 1 hour (Fig. 3).
Thirteen of the 15 wounded cats had a sharp rise in
MABP which began a few seconds after wounding,
peaked at approximately 1 minute, and at 4 minutes
returned to control levels where it remained for the
remainder of the experiment. Two cats showed a slight
fall in MABP 1 minute after wounding. The transient,
postwounding hypertension was significant for all three
wounded groups but the transient MABP rises after
wounding did not correspond with missile energy.
The ICP in control cats ranged from 6.7 _+ 2.5 to 7.2
_+ 3.3 m m Hg for the 1st hour of observation, then
gradually rose throughout the remaining 5 hours (Fig.
4). Immediately after wounding, all 15 cats exhibited
an abrupt large rise in ICP; pressure then fell over m a n y
minutes to a still-elevated but lower level that was
sustained. Both the immediate and long-lasting ICP
elevations were proportional to wound energy. In-
creases of ICP in the 2.50- and 1.40-J wounded groups
were significant.
The CPP of unwounded cats tended to rise through-
out the 1st hour of observation because of rising MABP;
this increase became significant at 20 minutes (Fig. 5).
In the wounded groups, CPP was uniformly elevated 1
minute after wounding due to the markedly elevated
200- oCONTROL
o0.9J
B1.4J
150- A2.5J
_> 6.0
-6
8.6 "I-
38.9 E IO0-
E
66.7 n
< 50-
; 10 2'0 3'0 4'0 5'0 60 1:20 2'~0 360
Time (mins)
Total
Cats FIG. 3. Graph showing mean arterial blood pressure
(MABP) in control and brain-wounded cats. The control
8 25 group of unwounded cats showed a gradual rise in MABP
5 10 during 1st hour of observation presumably because anesthesia
lessened. All wounded groups showed a significant transient
3 15
rise of MABP, commencing within several seconds of wound-
ing. Animals were wounded at time 0.
757
 M. E. Carey, et al.

80 oCONTROL to 30 minutes. Following this, the heart rate tended

o0.9J to return to control levels. One cat developed transi-
ml.4J
60 '~ ~,2.5J
ent tachycardia after wounding, and two had transient
m ' /,,\ tachycardia followed by bradycardia. These variable
effects of wounding precluded the almost universally
.EE 4 0 - ~,__; ~ _ . seen postwounding bradycardia from reaching statisti-
cal significance.
0 Respiratory frequency in all unwounded cats ranged
20- 9
i Oo ~ 9 . oj/ ~ 9 ~. ~ 9
from 13 to 15 breaths/min during the 1st hour of
observation. Ten of 15 wounded animals exhibited
reduced respiratory frequency immediately after
0 . . . . . ,I, ' 6
0 10 2'0 3 0 4 0 50 6 0 120 2 0 3 0 wounding; six became entirely apneic during the 1st
Time (mins) minute postwounding. In seven of the 10 cats that
exhibited a reduced respiratory rate after wounding a
FIG. 4. Graph showing intracranial pressure (ICP) in con-
trol and brain-wounded cats. The ICP in the control group normal breathing pattern returned within 3 minutes.
gradually rose after 1 hour as the depth of anesthesia lessened. Neither the occurrence rate nor the degree of respiratory
All brain-wounded cats exhibited prompt and sustained ICP depression (as reflected by changes in respiratory fre-
elevations which corresponded with the energy of the wound- quency) after wounding could be related to a specific
ing missile. The sustained ICP elevations occurring after 1.4- missile energy; three cats wounded at 0.90 J exhibited
J and 2.5-J wounds were significant.
respiratory depression, as did three wounded at 2.50 J.
Three cats had increased respiratory frequency after
injury.
MABP. Since MABP returned to baseline within 5
minutes of injury, subsequent CPP reductions were Arterial Blood Gases and p H
caused by persistent ICP elevations. Cerebral perfusion In the control group, the initial PaO2 averaged 88.8
pressure was reduced 5% in the 0.90-J injured cats, fell 4- 15.8 m m Hg, the PaCOz was 40.7 4- 5.5 m m Hg, and
23% after a 1.40-J injury, and was significantly de- the pH was 7.34 + 0.05. Twenty minutes after obser.
creased by 46% following a 2.50-J wound. vations began, the PaO2 had risen significantly to 99 +
17.2 m m Hg, and by 60 minutes it was 105.0 + 18.3
Changes in Heart Rate and Respiratory Frequency m m Hg. This reflects improved respirations consequent
The heart rate for all unwounded cats varied between to decreasing anesthesia. No significant changes in
161 ___ 11 and 1 9 5 _ 28 beats/min for the 1st hour of PaCO2 or pH occurred a m o n g cats in the control group
observation. Ten of 15 wounded cats exhibited tran- during the I st hour of observation.
sient bradycardia of 10% to 15% which began at times In the three experimental groups before injury, Pa0~
ranging from 189seconds after wounding and lasted 3 ranged from 89.9 + 10.6 to 102.1 _+ 16.2 m m Hgand
the PaCO2 from 38.4 -+ 5.0 to 41.0 4- 4.9 mm Hg,
Plasma p H varied from 7.35 4- 0.04 to 7.37 _+ 0.07. No
significant postinjury changes in arterial blood gas pres.
160- o CONTROL sures or p H occurred in the group with 0.90-J wounds,
eO.9J but three cats showed decreased plasma PaO2 and two
ml.4J
A2.5J
had increased PaCO2 during the 1st minute postwound-
120- ing. Animals wounded at 1.40 J showed the most:
. ell e
"I" ~--='• J ~ - I z 9 consistent and significant mean arterial blood gas and
i= 8 0 - p H alterations 1 minute after wounding: the Pa02
E . - . ~ _ f *q F --’r /"
.T-- ~t decreased to 55.7 _+ 12.7 m m Hg, the PaCO2 increased
n. to 46.6 + 4.9 m m Hg, and the p H fell to 7.30 + 0.05.
a.
(.) 40- The decreased plasma PaO2 level rose by 3 rninut~
postwounding, and by 10 minutes was no different from
the control PaO2 value. Plasma PaCO2 remained ele-
o 6 ib 2'o3'o4bgo6o12o ' 36o vated for 20 minutes after wounding, but the pH was
Time (rains)
reduced for 10 minutes. In cats wounded at 2.50 J,
blood PaO2 showed a significant reduction to 69.9 _+
FIG. 5. Graph showing cerebral perfusion pressure (CPP)
in control and brain-wounded cats. The CPP in the control 29.7 m m Hg at 1 minute, after which it increased to
group gradually rose during the first 60 minutes due to in- control levels. Although the postwounding plasma
creases in the mean arterial blood pressure (MABP). In all PaCO2 rose and the p H fell in this group, large standard
wounded animals, after an initial rise consequent to the tran- deviations precluded determination of a statistical sig-
sient rise in MABP, CPP was reduced for at least 30 minutes
due to an increase in intracranial pressure. The CPP reduction nificance for these altered variables. Postwounding
in the group with a 2.5-J wound approached levels whereby changes in arterial blood gases and p H could not be
brain energy failure might supervene. correlated with missile energy.

758 J. Neurosurg. / Volume 71/November, 1989

Experimental missile wound to brain
TABLE 3
Arterial hematocrit changes after wounding*
Hematocrit (%)
Missile No. of
Energy(J) Cats 1 Min 20 Min
Prewounding Postwounding Postwounding
0.90 4 31.6 _+4.9 38.9 _+6.9"~ 34.4 _+2.8
1.40 5 32.3 _ 3.6 40.8 _ 5.0I 33.1 _+4.2
2.50 5 32.8 -4-2.9 40.5 + 4.91- 33.8 _+4.3
2.50 3 27.3 _4-4.3 27.9 _+3.1 27.5 _+3.5
(spleneetomy)
*Valuesare means _+standard deviations.
tSignificant difference compared with prewound hematocrit (p <
0.05).
Changes in Blood Glucose Concentration
In the control group, the blood glucose concentration
became significantly (p < 0.05) elevated (89 _ 19 mg/
dlt0 112 _+ 27 mg/dl) after only 60 minutes of obser-
vation, whereas all wounded groups showed a rise
within 3 minutes o f injury. This rise became significant
10minutes after wounding in the group with a 0.90-J
wound(88 _+ 31 mg/dl to 138 + 46 mg/dl). A m o n g cats
wounded by a 2.50-J missile, the postwounding hyper-
glycemic increase was significant at 20 minutes (86 _+
21 mg/dl to 141 + 61 mg/dl). Postwounding hypergly-
cemia occurred in the group with a 1.4-J wound, but
was not significant. Although 14 of the 15 wounded
eats exhibited postwounding hyperglycemia, the varia-
bilityof control and postwounding blood glucose levels
in these unfasted animals reduced the number of "sig-
nificant" rises in blood glucose concentrations among
the wounded groups. No correlation between mis-
sileenergy and subsequent blood glucose levels was ap-
parent.
Changes in Hernatocrit
In all three groups of wounded animals arterial he-
mat0crit showed a significant rise within 1 minute of
injury but then returned to prewounding levels 5 to 20
minutes after injury (Table 3). Splenectomy abolished
this effect. In normal cats the hematocrit varies from
24% to 55%, accounting for the wide variation in
prewounding findings.’5
Discussion
Ballistic Considerations
Physical Correlates o f Missile W o u n d i n g in Gen-
eral. Missile wounding can only be understood in
terms of the physical interactions between the missile
and the tissue through which it passes. The primary
destructive effect of a missile interacting with tissue is
caused by the crushing action of the missile it-
~lf. 14"2~ Besides this direct action, however, a missile
moving in a water or tissue medium generates three
distinct types of pressure within the medium which it
transits:2o.2~.25
1. Juxta-missile pressure. Extremely high pressures
J.Neurosurg. / Volume 7I/November, 1989
(thousands of atmospheres) are generated immediately
in front of and at right angles to a moving missile owing
to flow of the medium in which the missile is traveling
around the missile.
2. Longitudinal, "strong" shock wave pressure. When
a missile strikes an object, a high-pressure compression
front or shock wave is formed which, in tissue, moves
spherically away from the missile strike-point at ap-
proximately the velocity of sound in water (approxi-
mately 1460 m/sec). The longitudinal, "strong" shock
pressure wave initially has a very steep front but its
shape and duration wave may be changed with propa-
gation through a medium, particularly one that is not
homogeneous, such as tissue. As it travels, therefore,
the steep front of a "strong" shock wave will become
less steep and, finally, will assume the characteristics of
an "ordinary" pressure wave (see below). In water, the
peak pressure of a "strong" shock wave may exceed 80
arm but the entire "strong" shock wave event lasts only
about 10 usec. Blunt missiles may cause "strong" shock
waves with strike velocities as low as 60% of the velocity
of sound in the medium. Some investigators 21 have
thought that, in the absence of fluid to air trans-
fer, "strong" pressure waves do not cause tissue dam-
age because their brief duration prevents transfer of
sufficient energy to surrounding tissues to distort and
tear them.
3. Pressure waves from kinetic energy transfer. When
a missile passes through tissue, kinetic energy is trans-
ferred to nearby tissue elements which are propelled
radially from the missile track, creating a large subat-
mospheric temporary cavity directly behind the missile.
When the elastic limit of this outwardly displaced tissue
is reached, it falls inward whence it was displaced. This
cycle may be repeated several times before the deranged
tissue comes to rest around the permanent track created
by the missile. The oscillating, outward and inward rush
of tissue creates a long-lasting (milliseconds) lower am-
plitude (20- to 30-atm) pressure wave which propagates
widely throughout the medium. It has been considered
that these lower-amplitude, longer-duration pressure
waves are the cause of damage to tissues at a distance
from the site of actual missile injury.
The a m o u n t of tissue damage caused by a missile
may be correlated with the a m o u n t of energy deposited
within the tissue by the missile. 25-39This is expressed by
the equation: Ed = Een - Eex, where Ed = missile energy
of deposit, Een = energy of entry, and Eex = energy of
exit. If a missile is retained within the tissue, E~x = 0
and all missile energy will be given to the tissue. If the
missile exits, only part of its kinetic energy will be
deposited within the tissue. The same amount of energy
may be deposited by a small-mass missile with a large
velocity or a greater-mass missile with a smaller veloc-
ity. Kinetic energy deposited by a missile is partitioned
between that which directly crushes tissues in its path
and that which displaces tissues adjacent to the missile
track. 14 The latter is less destructive than the former
owing to the elastic properties of the displaced tissue
759

which m a y be deformed without being irrevocably de-
stroyed (L Sturdivan, personal communication, 1988).
P h y s i c a l Correlates o f a M i s s i l e W o u n d to the
Brain
Most wounds in combat are caused by small frag-
ments. 1 It was determined that 80% of all wounds
sustained at Dunkirk were caused by "splinters" 5 m m
or less in diameter. 3 Fragments weighing 110 to 220 mg
inflicted most fatal brain wounds in Vietnam (Carey
ME: Unpublished data from analysis of casualties sur-
veyed by the W o u n d Data and Munitions Effectiveness
T e a m (WDMET) in Vietnam). For this reason our
laboratory gun was designed to fire a very small (31.7-
mg) missile instead of a larger (310- to 870-mg) projec-
tile as used by prior investigators. 6 L~.~.3o Utilization
of a smaller, high-velocity missile in our experiments
may explain some of the physiological differences ob-
served by us as compared to prior brain-wounding
experiments which utilized larger missiles fired at lower
velocities. 6-~o,~~,,3o
The developed laboratory gun propels a small sphere
with enough velocity to penetrate the intact skulls of
laboratory animals avoiding the necessity of creating a
brain wound by firing through a previously placed
trephine. 6-~~176 Creating a nonfatal brain wound by
shooting a missile through the intact skull imposes
specific velocity and energy limits. In our experimental
model, the lower ballistic limit (238 m/sec, 0.90 J) was
that required for consistent skull penetration while the
upper limit (389 m/sec, 2.50 J) was that which produced
a fatal apnea in the great majority of instances (even
though the missile did not directly damage brain-stem
respiratory centers). Thus, wounding the experimental
animal through the intact skull greatly reduces the
spectrum of realistic missile velocities and energies
available for the creation of a nonfatal wound. In our
model, the missile does not exit so that all missile energy
is deposited within the brain.
Ballistics research on animals to simulate h u m a n
wounds involves significant animal-human scaling
problems. 25 The cat provides a 25-gm brain for our 31.7
mg experimental missile. The combat soldier has a
1300-gm brain and is often wounded by shell fragments
with a mass of 100 to 200 mg. Accordingly, our test
missile has a mass seven to 15 times too large. We have
chosen to accept this scaling factor because constructing
a test system to fire a smaller missile would be techni-
cally very difficult and to increase the size of the labo-
ratory animal would m a k e the experiments cost-prohib-
itive. Use of smaller experimental animals such as
rabbits with a 7-gm brain or rats with a 1-gm brain
would grossly distort the brain-missile ratio, making
experimental findings of questionable significance rel-
ative to humans. Furthermore, the cat’s brain is archi-
tecturally more akin to the h u m a n brain than that of
either the rabbit or the rat.
In the present model, tissue damage can be expected
to be caused by the direct action of the missile upon
760
M . E. C a r e y , et al,
tissues which it encounters and by "ordinary" pressure
waves caused by kinetic energy transfer from missile to
brain. These pressure waves may be widely transmitted
throughout the brain. Theoretically, "strong" shock
waves would not be created in our model because
missile velocities do not approach 870 m/sec.
Effect o f W o u n d i n g on B r e a t h i n g
The neuronal substrate for respiratory control is com.
plex and extends from the cerebral cortex through the
medulla from which emanates the primary inspiratory
and expiratory rhythm. -~333 The basic oscillating respi-
ratory rhythm produced by the medullary neuronal
network may be modified by pontine, mesencephalic,
diencephalic, limbic, and cortical influences? 3 Stimu-
lation of various cortical and subcortical areas may
cause respiratory a r r e s t . 2"27"3442"47 Increases in systemic
arterial blood pressure, such as occur after brain wound.
ing, also m a y lead to temporary apnea. 26
The occurrence of postwounding respiratory arrest
in 83 cats wounded through a completely intact skull
became greater as missile energy increased (Table 1).
Other experimental studies on brain injury also found
apnea to be a prominent feature. Nilsson, et al.,37
impacted the closed skull of rats with a 600-gin piston
and observed the onset of apnea when piston velocity
exceeded 9 m/sec. Fluid-percussion injury models in
the rabbit 4~ and cat 45 have shown the occurrence of
permanent apnea with impact pressure peaks above 2.5
atm. Crockard, et al., 9 observed that a 0.5-J missile
injury through a trephine opening into a monkey’s
brain caused no respiratory dysfunction; a 1.3-J wound
caused the respiratory rate to slow, and a 5.0-J missile
wound produced immediate apnea in four of seven
animals. Fluid-percussion models have shown that,
upon impact, a marked pressure difference exists b~
tween the intracranial and spinal spaces, which pro.
motes rostral-caudal displacement of the intracranial
contents. This m o v e m e n t might distort the brain stem
and lead to postpercussion apnea. 31 Actual brain-stem
displacement following percussive injury to the cere-
b r u m has been documented with x-ray flash cinema-
tography. ~8 In our model, we have shown that passage
of the missile through the brain generates a high ICP
(Fig. 4). This might cause transient herniation of cere-
bral tissue from the intracranial to the intraspinal space,
distort the brain stem, and affect medullary respiratory
centers.
Another mechanism to explain missile-induced ap-
nea might be the effect of "ordinary" pressure waves
caused by kinetic energy transfer from the missile to
the surrounding brain. These pressure waves might
propagate to the brain stem and impair medullary
neural function in general and respiratory neurons spe-
cifically. Evidence for widespread medullary dysfunc-
tion in our model includes an almost universally ob-
served bradycardia seen after wounding. Perhaps the
close proximity of the medullary respiratory nuclei to
the floor of the fourth ventricle somehow accounts for
J. Neurosurg. / Volume 71/November, 1989
Experimental missile wound to brain
the particular vulnerability of these cells to the indirect
effectsof the missile wound.
Missile injury in the present model produced an
ablative cortical lesion rather than a stimulatory one.
Whereas stimulation of cortical regions m a y cause res-
pirations to cease, we are unaware of experiments where
cortical ablations alone cause cessation of breathing.
Therespiratory arrests observed after hemispheral brain
wounding in our model, therefore, are most likely
caused by a direct medullary effect. Because the apnea
was often permanent, it was unlikely to have been
caused solely by the transient postwounding hyperten-
sion which occurred a few seconds after missile pas-
sage.2~’
The present experiments were conducted with cats
under pentobarbital anesthesia, a respiratory depres-
sant, and with an anteroposterior missile trajectory
offset20 ~ from the sagittal plane. Whether the observed
apneawould be significantly modified by use of another
anesthetic agent, a different missile trajectory, or a
primate brain with its different configuration is un-
known. Nevertheless, the present data indicate that
missile-induced apnea in the cat was often prolonged
butalso frequently reversible if respiratory support were
givensoon after the onset of apnea.
These findings in cats, extrapolated to humans, sug-
gest that following a lower-energy brain wound to a
cerebral hemisphere, the integrity of medullary respi-
mt0ry centers may be the predominant factor which
determineswhether an individual lives or dies, provided
excessiveintracranial bleeding does not occur. A lower-
energyhemispheral wound may not appreciably affect
respiration, a somewhat higher-energy wound m a y
causetransient apnea, while a yet higher-energy wound
might irreversibly damage the medullary respiratory
centers and cause death from apnea. This mechanism
may explain deaths from brain wounding where the
missile does not directly injure a vital structure and
where intracranial bleeding is not excessive. Possibly
romeindividuals who have sustained hemispheral brain
wounds and who are thereby rendered apneic m a y be
saved, provided that respiratory support (such as
m0uth-to-mouth breathing) is given within a few mo-
ments. If respiratory support is delayed, secondary hy-
l~xic brain damage or death m a y ensue. It may be
impossibleto tell immediately after injury which person
witha brain wound has reversible or irreversible apnea.
Therefore, all who sustain a penetrating missile wound
to the brain should probably be provided immediate
respiratory support if they have severely depressed res-
pirationsor are apneic. Our data suggest that respiratory
support should be maintained for several hours unless
otherfindings indicate brain death, because spontane-
ous respiration m a y resume after even a prolonged
l~ri0d of apnea.
Selected Central and Peripheral Physiological
Effects
The data presented here were derived from 20 cats
whichhad an ICP monitor inserted before wounding.
J.Neurosurg./ Volume 71/November, 1989
MABP, 1CP, and CPP Following Wounding. The
transient increase in MABP observed within seconds of
brain wounding followed by return to baseline over the
next several minutes presents a pattern similar to that
observed in cerebral percussion models involving rab-
bits, 4-~cats, 4~ and rats, 37 and is unlike that demonstrated
by trephinated missile-wounded primates. ’~In monkeys,
a 1.3-J missile wound to the brain caused a triphasic
blood pressure response: immediately after wounding
MABP decreased, 5 to 15 minutes later it increased
above control levels, and thereafter it decreased signif-
icantly below baseline values.
The brief postwounding hypertension observed in
our model may have been incited by brain (probably
medullary) mechanisms acting reflexly through the
sympathetic nervous system because the hypertension
response c o m m e n c e d several seconds after wounding.
In percussion-injury experiments, postinjury hyperten-
sion could be abolished by cervical spinal cord transec-
tion implying that a descending spinal pathway medi-
ated this response. 45
Both mild and fatal percussion injuries to the brain
m a y produce hypotension immediately after impact. 3~
Since only two of 15 cats in the present study became
hypotensive, this effect was not a prominent feature in
our model. The lowest missile energy of 0.90 J which
we used probably did not create a "mild" brain injury.
We have excluded high-energy, inherently lethal wounds
from our study.
The immediate and sustained ICP elevations seen
after brain wounding must not be confused with instan-
taneous intracranial overpressures generated by missile
passage through the brain. Intracranial overpressures
associated with the "ordinary" pressure waves of missile
transit last about 10 msec and cannot be recorded on
our physiograph. 2~ The observed elevations in ICP oc-
curred over a much longer time period and were caused
by intracranial physiological-anatomical events associ-
ated with brain wounding. The ICP increases could
have come from several sources: 1) associated intracra-
nial hemorrhage; 2) an increased rate of cerebrospinal
fluid (CSF) formation or decreased rate of CSF absorp-
tion; 3) associated vasogenic brain edema; or 4) an
increase in the intracerebral vascular volume.
Measuring the a m o u n t of intracranial bleeding as-
sociated with the brain wound is difficult. Our experi-
ence, however, indicates that higher-energy wounds
were not necessarily associated with more intracranial
bleeding; sometimes lower-energy wounds caused larger
intracerebral clots than did higher-energy lesions. A
lower-energy missile would be just as likely to sever a
cerebral vessel as a higher-energy missile. Thus, if intra-
cranial bleeding alone were responsible for the observed
sustained increases in ICP one might expect a more
random distribution of ICP elevations a m o n g groups
instead of a stepwise increase in ICP change with each
incremental increase in missile energy deposit (Fig. 4).
We are, therefore, inclined to discount associated intra-
cranial hemorrhage as being the sole factor accounting
for postwounding ICP elevations.
761

Our experiments on postwounding vasogenic brain
edema indicate that no significant brain edema occurs
within 6 hours of wounding by either 0.90-J or 1.40-J
missiles (unpublished data). Thus, increased brain wa-
ter does not account for the immediate and early rise
in ICP.
Missile wounding of the brain appears to excite a
sympathetic response, manifest by transient hyperten-
sion and increasing peripheral blood glucose levels, and
a parasympathetic effect, exemplified by bradycardia.
Sympathetic stimulation has been shown to decrease
the rate of CSF formation 32 while parasympathetic
stimulation may increase it. 22 Whether parasympathetic
(cholinergic) stimulation consequent to brain wounding
might increase the rate of CSF formation in brain-
wounded cats or whether blood in the CSF might
decrease its absorption is unknown. The latter mecha-
nism, particularly, would tend to raise postwound-
ing ICP.
Increased intracerebral vascular volume following
wounding also m a y account for the stepwise increase
in ICP with increasing wound energy. Cerebral hyper-
emia has been hypothesized following closed head
injury 2829 and may occur as well after a missile wound
to the brain. If the intracerebral vascular volume does
increase after brain wounding, medical therapies which
expand the intracerebral vascular space further may
prove detrimental to the wounded brain because ex-
panding the intravaseular volume would elevate the
ICP further.
Just as ICP values showed a stepwise increase with
rising wound energy, the CPP’s had a corresponding
decrease. Long-lasting and serious metabolic derange-
ments within the brain occur when CPP is reduced
below 40 m m Hg. 49 The 2.5-J missile injury reduced
CPP’s to about 50 m m Hg 3 to 20 minutes after injury.
Higher-energy missile injuries to the brain, therefore,
might be associated with severe CPP reductions where
metabolic abnormalities m a y supervene and c o m p o u n d
the effects of direct missile damage. Crockard, el al.fl
also observed persistently elevated ICP’s and reduced
CPP’s following brain wounding in primates; the initial
ICP elevations appeared missile-energy dependent.
Fluid-percussion injury of the brain produces only a
brief increase in ICP consequent to the brief rise in
MABP immediately after impact. 45 This injury, there-
fore, differs greatly from a missile wound.
Changes in Cardiac Rate. Bradycardia beginning
about 2 seconds after the event has been rather uni-
formly observed following brain injury, be it percus-
sive 43’4s o r following missile trauma. This may result
from stimulation of brain-stem parasympathetic cen-
ters due to brain-stem distortion or m a y reflect a re-
flex baroreceptor response from the injury-induced
increase in MABP. 37 Although we observed no relation-
ship between the degree of bradycardia and wound
energy, others have noted heart rate slowing to be
greater the more severe the brain injury. 37
Changes in Arterial Blood Gases, pH, and Respi-
762
M. E. Carey, et al.
ratory Frequency. Ten of the 15 wounded cats had a
reduced respiratory rate after wounding, presumably
from brain-stem effects resulting from high intracranial
overpressures generated by the wounding missile. Vio-
lating the closed cranial vault to insert our chosen
epidural pressure transducer, however, abolished pro-
longed (_> 6-minute) postwounding apnea which wasa
prominent feature when cats were wounded through a
completely intact skull (Table 1). Possible reasons for
this include trephination (even though the cranial defect
was sealed with acrylic) and the volume of the air-filled
monitor itself. The small a m o u n t of air within the
epidural pressure-sensing balloon may have been
enough to absorb some of the missile energy and protect
the brain stem.
Since brain wounding generally slowed the respira-
tory rate or caused apnea, it is not surprising that many
of the brain-wounded cats had decreased PaO2 and pH
and increased PaCO~ immediately after wounding.
These results in cats differ from those reported for
comparably wounded monkeys, k) Monkeys wounded
at 1.3 J showed a diminished respiratory rate but an
increased tidal volume without alterations in arterial
blood gases or pH.
Changes in Blood Glucose Concentration. Catsin
the control group showed a progressive rise in blood
glucose values during the 1st hour after induction of
anesthesia in the stereotactie frame, attributed to di.
minishing anesthesia and consequent stress, although
all cats appeared asleep. All of the wounded groups
showed a prompt rise in blood glucose concentration
following the brain wound. Both stress and intracranial
lesions are c o m m o n l y associated with a rise in arterial
blood glucose levels due to catecholamine release and
gluconeogenesis. 4~ Theoretically, large postwounding
elevations in blood glucose concentrations could prove
detrimental to brain function if brain ischemia were
caused by the missile wound. Elevations in blood glu-
cose levels aggravate ischemic brain damage, presuma-
bly from increased lactic acid production in the dam-
aged brain. Excessive lactic acid in the tissue adds to
ischemic tissue damage. 17.41
Changes in Hematocrit. The transient increase in
hematocrit following brain wounding was mediated by
splenic contraction and injection of red blood cellsfrom
the spleen into the circulation, because this immediate
postwounding response was abolished by splenect0my
(Table 3). We infer that this splenic response was me-
diated by sympathetic stimulation following the brain
wound. Arterial resistance and venous capacitance ves-
sels in the splenic capsule have a dense sympathetic
adrenergic innervation which, when excited, contract
the vascular smooth muscle and expel blood from the
spleen. In the cat, splenic nerve stimulation results in
the discharge of large volumes of splenic blood with a
hematocrit of 70% to 80%. ~2 Increased hematocfit
slows blood flow; if the flow were reduced sufficientIy,
ischemic brain damage could theoretically be superim-
posed upon the mechanical damage associated with
J. Neurosurg. / Volume 71/November, 1989
Experimental missile wound to brain
missile passage. 4~ T o o u r knowledge, this is the first
demonstration o f t r a n s i e n t l y increased arterial h e m a t -
0critfollowing b r a i n w o u n d i n g . N o i n f o r m a t i o n on this
subject in m a n exists.
Acknowledgment
]’he authors thank Dan Torbati, Ph.D., who made many
helpfulsuggestions for this manuscript.
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Manuscript received July 1, 1988.
Accepted in final form July 20, 1989.
This research was supported by the U.S. Army Medical
Research and Development Command, Contract DAMD-18-
83-C-3145.
Opinions expressed are those of the authors and are notto
be construed as an official Department of the Army position.
Address reprint requests to: Michael E. Carey, M.D.,
Department of Neurosurgery, Louisiana State University
Medical Center, 1542 Tulane Avenue, New Orleans, Loui-
siana 70112.
J. Neurosurg. / Volume 71/November, 1989