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The efficacy of semax in the treatment of patients at different stages of

ischemic stroke

Article in S.S. Korsakov Journal of Neurology and Psychiatry / Ministry of Health and Medicine of the Russian Federation, All-Russia Society of neurologists [and] All-Russia Society
of psychiatristы · January 2018
DOI: 10.17116/jnevro20181183261-68

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https://doi.org/10.17116/jnevro20181183261-68

The efficacy of semax in the treatment of patients at different

stages of ischemic stroke
E.I. GUSEV 1, M.YU. MARTYNOV 1*, E.V. KOSTENKO 1,2, L.V. PETROVA 2, S.N. BOBYREVA 2

1
Pirogov Russian National Research Medical University, Ministry of Health of Russia, Moscow, Russia; Moscow Centre for Research and Practice in Medical
Rehabilitation, Restorative and Sports Medicine, Moscow Healthcare Department, Moscow, Russia
Objective. To evaluate the efficacy of semax and timing of rehabilitation on the dynamics of plasma BDNF levels, motor performance, and
Barthel index score in patients after ischemic stroke (IS). Material and methods. One hundred and ten patients after IS (43 men, 67 women,
mean age 58.0±9.7, Me 63 years) were examined. All patients were divided into early (89±9 days) and late (214±22 days) rehabilitation groups.
Each group was subdivided into semax+ and semax− subgroups. Standard regimen of semax included 2 courses (6,000 mcg/day) for 10 days
with 20 day interval. Plasma BDNF levels, motor performance on the British Medical Research Council scale and Barthel index were assessed in all
groups. Results. Administration of semax, regardless of the timing of rehabilitation, increased BDNF plasma levels which remained high during
the whole study period. In semax− subgroups high BDNF plasma levels were positively correlated with early rehabilitation. Administration of
semax and high BDNF levels accelerated the improvement and ameliorated the final outcome of Barthel score index. There was a positive
correlation between BDNF plasma levels and Barthel score, as well as a correlation between early rehabilitation and motor performance
improvement. The correlation between BDNF plasma levels and Barthel score was modified by the timing of rehabilitation. Conclusions. Early
rehabilitation and administration of semax increase BDNF plasma level, speed functional recovery, and improve motor performance.

Keywords: stroke, rehabilitation, semax, neuropeptide metabolic drugs, brain derived neurotrophic factor (BDNF), Barthel index.

© Team of authors, 2018 *e-mail: m-martin@inbox.ru

JOURNAL OF NEUROLOGY AND PSYCHIATRY, 3, 2018; Issue 2 61

 Ischemic stroke (IS) is one of the main causes of
disability. After IS more than 30% of patients need
constant care, almost 20% have difficulties with
independent movement and only 10-15% return to job
[1, 2]. The plasticity of the nervous system plays an
important role in the restoration of functions after IS.
Experimental and clinical data indicate that the
plasticity can be influenced by combinations of
pharmacological agents and individualized
rehabilitation programs [3-5].
During rehabilitation after IS, special attention is
primarily paid to growth and trophic factors for
restoring motor functions. These factors stimulate the
processes of neuroplasticity, contribute to the growth
of muscle strength and motor activity, and improve
the functional outcome [6, 7]. The neurotrophic factor
of the brain (Brain-Derived Neurotrophic Factor or
BDNF) is one of the main trophic factors involved in
the processes of neuroplasticity and restoration of
functions after focal CNS damage [3, 8]. After a
stroke, the level of BDNF correlates with the degree
of recovery of motor functions [9, 10]. Intravenous
administration of BDNF to rats with photothrombotic
IS significantly improves recovery of their motor
functions and behavior [11].
In experimental studies [9, 12], it was shown that
the BDNF content in the brain varies during different
periods of IS and depends on many factors, including
the ongoing rehabilitation measures. In turn, the
rehabilitation activity, in particular the intensity of
aerobic exercises, can affect the level of BDNF [9]. In
addition, time of the rehabilitation start after IS affects
the BDNF level. For example, its early start is
distinguished with a more significant BDNF increase
[13] along with a better functional outcome [14]. In
addition to the time that has passed since both a stroke
and the beginning of rehabilitation measures, the
content of BDNF in tissues can determine the
medication taking. Thus, the atorvastatin
administration after experimental IS increases the
BDNF expression in the brain [15]. In clinical studies,
it was shown that the plasma BDNF content of
patients with atherothrombotic IS also increased after
atorvastatin taking [16].
One of the medications taken in the acute IS
period is semax which is a synthetic heptapeptide
(fragment of ACTH4-10) with the sequence
methionyl-glutamyl-histidyl-phenylalane-prolyl-
glycyl-proline: H-Met-Glu-His-Phe-Pro-Gly-Pro-
OH (formula C39H55N9O12S with molecular weight
873,97 Da) [17]. The semax mechanism of action
includes modulation of cellular metabolism in the
limbic system with the cycloAMP hyperproduction,
62
increasing of the level of monoamines, activity
increasing of acetylcholinesterase and dopamine
receptors in the brain [18, 19]. An important feature
of the medication is the speed of the positive
therapeutic effect, without development of the
medication dependence and without withdrawal
symptoms. After intranasal administration, semax
goes through the blood-brain barrier in few minutes.
With a single administration, the therapeutic effect
lasts up to 24 hours. The semax prolonged action is
due to its successive transformation, while most of the
medication properties are preserved in its fragments
EHFPGP (Glu-His-Phe-Pro-Gly-Pro) and HFPGP
(His-Phe-Pro-Gly-Pro). Both EHFPGP and HFPGP
fragments are sufficiently stable and independently
modulate cholinergic neurotransmission and nitric
oxide synthesis [17, 19]. In the IS acute period semax
has a neuroprotective, neurometabolic and antioxidant
effect, and also contributes to the BDNF and nerve
growth factor synthesis in the brain [20, 21].
The objective of the research is to study how both
the semax effect and the rehabilitation start time
influence on the BDNF dynamics in the blood, the
intensity of recovery of motor functions and
functional activity of patients after IS.
Material and methods used
There were 110 patients examined in the IS
recovery period: 43 (39.1%) males and 67 (60.9%)
females aged 29 to 73 years old (mean age is 58.0 ±
9.7 years old, Me is 63 years old). The IS diagnosis in
all cases was confirmed by CT or MRI of the brain.
Depending on the start time of the rehabilitation
programs, 2 groups were formed (Table 1). The first
group included 60 patients whose rehabilitation
started after 89 ± 9 days from the disease start (early
rehabilitation), the second group included 50 patients
whose rehabilitation started after 214 ± 22 days (late
rehabilitation). In turn, each group was randomly
divided into subgroups of patients who took semax
(subgroups 1a and 2a with early and late
rehabilitation, respectively) and who did not take it
(subgroups 1b and 2b with early and late
rehabilitation, respectively). In subgroup 2a, the time
between the IS development and the rehabilitation
start was significantly greater than in subgroup 2b.
Concerning the rest factors, the both groups and
subgroups are completely consistent (see Table 1).
The research protocol included a study of the
dynamics of the paresis development in arm and leg,
the total score of the Barthel scale, plasma BDNF
content, semax tolerance and treatment effectiveness.
JOURNAL OF NEUROLOGY AND PSYCHIATRY, 3, 2018; Issue 2
 Table 1. Demographic and clinical data of patients involved into the study

The 1st group The 2nd group

Indicator The 1a subgroup The 1b subgroup The 2a subgroup The 2b subgroup
Total (n=60) Total (n=50)
(n=30) (n=30) (n=30) (n=20)
Age, years old 54.6±5.8 56.3±4.9 52.8±6.6 57.3±6.7 56.5±7.1 58.3±6.4
Gender
Males 22 (36.7/%) 12 (40/%) 10 (33%) 21 (42%) 12 (40%) 9 (45%)
Females 38 (63.3%) 18 (60%) 20 (67%) 29 (58%) 18 (60%) 11 (55%)
Focus of disease
Right side 24 (40%) 12 (40%) 12 (40%) 21 (42%) 11 (37%) 10 (50%)
Left side 28 (47%) 15 (50%) 13 (43%) 25 (50%) 16 (53%) 9 (45%)
Vertebrobasilar system 8 (13%) 3 (10%) 5 (17%) 4 (8%) 3 (10%) 1 (5%)
Timespan after the stroke, days 89±9 91±8 87±10 214±22 231±25 188±29*
Motor impairment
Right side 28 (47%) 14 (46%) 14 (46%) 21 (42%) 12 (40%) 9 (45%)
Left side 15 (25%) 8 (27%) 7 (23%) 16 (32%) 10 (33%) 6 (30%)
Absent 17 (28%) 8 (27%) 9 (31%) 13 (26%) 8 (27%) 5 (25%)
Muscle strength, score
Upper limb 3.2±0.2 3.1±0.2 3.2±0.2 3.1±0.2 3.1±0.2 3.1±0.2
Lower limb 3.0±0.2 3.0±0.2 2.9±0.2 3.1±0.1 3.3±0.1 2.9±0.1
Barthel scale, score 58.5±2.7 58.2±2.6 58.8±2.6 59.8±2.5 60.5±2.5 58.8±2.5
BDNF, pg/ml 8.3±1.1 7.8±1.1 8.6±1.0 8.0±1.2 8.1±1.2 7.9±1.5

Note. * — Differences are significant between 2a and 2b subgroups when t=8.35 and p=0.0000.
Table 2. Protocol of evaluation of the clinical and laboratory indicators and treatment effectiveness throughout the study

1st visit 2nd visit 3rd visit 4th visit

Indicator
(involving patients into study) (1 month later) (2 months later) (5 months later)
Paresis degree of upper limb + + + +
Paresis degree of lower limb + + + +
Barthel scale + + + +
BDNF + + − +
Semax acceptability + + + −
Treatment efficacy - + + +

Examination of patients took place at four visits:
initial (randomization and inclusion into the study),
then after 1st, 2nd and 5th (final) months (Table 2).
To assess the paresis degree, there is a 6-point scale
for assessing muscle strength of the British Medical
Research Council [22]. The study of activity in
everyday life and functional independence was carried
out using the Barthel scale, including an analysis of
each of its sections [23]. The BDNF content in the
serum was determined by the solid-phase enzyme-
linked immunosorbent assay using the Human BDNF
Immunoassay kit (R&D Systems, USA) as to the
manufacturer's method. The obtained BDNF values
were compared with the normative indicators: 0 to15
pg / ml is low level, 15 to 30 pg / ml is average level,
more than 30 pg / ml is high level.
The treatment in both groups was standardized and
included medication therapy, exercise therapy,
mechanotherapy, biological feedback methods,
massage, individual and group psychotherapy.
Patients of subgroups 1a and 2a, along with the
indicated therapy, were prescribed with the 1% semax
solution, 2 drops in each nasal passage 3 times a day
(6,000 µg / day) for 10 days (1st course). 20 days after
the end of the 1st course, the treatment was repeated.
The research results were entered into an
individual protocol and were subsequently
statistically processed using Excel, EpiStat 7.0 and
Statistica 6.0 software. Descriptive statistics for the
normal distribution of a characteristic (as to the
Kolmogorov-Smirnov test results) was presented as a
mean and a standard error of the mean (SD) or average
error of mean error (m), as well as a median (Me). In
addition, descriptive statistics of qualitative
characteristics were presented in the form of absolute
and relative frequencies (%). To compare two
independent groups using the same characteristic, the
Yeats-adjusted χ2 criterion was used with the odds
ratio (OR) and the 95% confidence interval (CI).

JOURNAL OF NEUROLOGY AND PSYCHIATRY, 3, 2018; Issue 2 63

Differences were considered statistically significant
when p <0.05.
Results
Effect of both semax and rehabilitation start time
on the BDNF level
In the beginning when the study had been initiated,
the plasma BDNF level was low and did not differ
between groups with early and late rehabilitation (see
Tables 1 & 3). 1 month after the start of rehabilitation,
the BDNF level in all subgroups, except of subgroup
2b, significantly increased compared to initial values
and reached an average level (Table 3). After 5
months, the BDNF level in subgroups 1a, 1b and 2a
decreased compared to the 1st month end, but
remained significantly higher than the initial values.
In subgroup 2b at the 1st month end, there was a
tendency to a significant increase in the BDNF level
(see Table 3), which disappeared by the end of the
observation, and the BDNF level in this group
remained low throughout the study.
Semax treatment affected the BDNF level and
dynamics, the differences between the 1st and 2nd
groups were significant throughout the study.
Moreover, the semax presription eliminated the
rehabilitation start time influencing on the BDNF
level and dynamics. So, in 1a and 2a subgroups, the
BDNF dynamics and increment value (Δ) did not
differ from each other, but significantly differed from
subgroups 1b and 2b. After 1 month from the start of
observation in 1a and 2a subgroups, the BDNF
increase reached 191.3 and 187.7% compared to the
initial level, while in 1b and 2b subgroups it was 112.8
and 56.9 %, respectively, which led to significant
differences between the subgroups. After 5 months,
the differences persisted: with early rehabilitation in
the 1a subgroup, the BDNF increase was 150.1%
compared to the initial level, in the 1b subgroup it was
45.3%, and with late rehabilitation 154.3 and 35.4%,
respectively (see Table 3). In addition, in the 1a
subgroup, its level from the 1st month end to the study
Table 3. The dynamics of the BDNF level of the examined patients (M±m)
Group Initially
1st (Early rehabilitation)
The 1a subgroup 7.8+1.1
The 1b subgroup 8.6+1.0
2nd (Late rehabilitation)
The 2a subgroup 8.1+1.2
The 2b subgroup 7.9+1.5
Note. * — differences are significant compared to initial indicators when t≥2.0 and p≤0.05; ** — tendency to significant differences compared initial indicators when
t=2.03; and p=0.052; *** — differences are significant between subgroups 1a and 1b subgroups when t=2.62 and p=0.011; # —differences are significant between 1a and
1b subgroups when t=3.44 and p=0.001; ## — differences are significant between 2a and 2b subgroups when t=4.86 and p=0.000; ### — differences are significant between
2a and 2b subgroups when t=4.12 and p=0.000; t — differences are significant between 1b and 2b subgroups when t=2.40 and p=0.021.
64
end time decreased by 20.8% (3.1 ± 1.7 pg / ml), while
in the 1b subgroup the decrease was 57.7% (5.6 ± 1.3
pg / ml; t = 2.92; p = 0.011). In the 2a subgroup, the
BDNF level from the 1st to the 5th month decreased
by 22.4% (2.8 ± 2.5 pg / ml), in the 2b subgroup it
decreased by 50.0% (1.4 ± 1.5 pg / ml; t = 2.25; p =
0.029).
In patients who did not take semax, the BDNF
level increase depended on the time of the
rehabilitation start. So, in the 1b subgroup after 1
month, there was a significant higher absolute and
relative BDNF than in the 2b subgroup, which was
112.8% and 56.9% respectively. By the end of the
observation period, the differences between these
subgroups still sustained as 41.9% and 28.7% (a
tendency to significant differences when t = 1.81; p =
0.087) (see Table 3).
Thus, the semax use leveled the influence of the
rehabilitation start time onto the BDNF indicators.
The medication contributed to the more rapid BDNF
level increase in the 1st rehabilitation month and to
maintaining its high and uniform concentration
throughout the entire observation period. In 1b and 2b
subgroups, the BDNF dynamics and growth depended
on the rehabilitation start time, and the early
rehabilitation led to a larger and more rapid BDNF
level increase.
The effect of the semax use and the rehabilitation
start time on the intensity of motor disorders
In the beginning when the study had been initiated,
43 (71.7%) patients of the 1st group and 37 (74.0%)
patients of the 2nd group had motor disorders in the
form of hemiparesis, while their initial intensity did
not differ between the groups (see Table 1). When
analyzing the effect of the rehabilitation start time on
the dynamics of motor disorders, in the 1a and 1b
subgroups a statistically significant increase in
strength in the lower and upper limbs was found after
1 month (Table 4) which maintained throughout the
all study period.
BDNF level, pg/ml BDNF incremental growth (Δ), pg/ml
1 month later 5 months later Initially — 1 month later Initially — 5 months later
22.6+1.6* 19.4+2.2* 14.9+1.3*** 11.7+1.7#
17.9+1.4* 12.2+1.5* 9.7+1.5t 3.9+1.5
23.6+2.1* 20.8+2.8* 15.2+1.7## 12.5+1.9###
12.3+1.6** 10.7+1.4 4.5+1.4 2.8+1.3
JOURNAL OF NEUROLOGY AND PSYCHIATRY, 3, 2018; Issue 2
A significant increase in strength in the limbs was
observed only in the end of the observation in 2a and
2b subgroups. The increase in strength in the arm by
the 1st month end in the 1a & 1b subgroups was
significantly ahead of similar indicators in 2a and 2b
subgroups. So, after 1 month of the rehabilitation start
n the 1a & 1b subgroups, muscle strength in the upper
limb recovered by 89.4 and 97.8% respectively
compared to the final assessment, while in 2a and 2b
subgroups recovery at a similar time point compared
to the final assessment, was 54.2% and 47.3% only.
The final arm recovery was also better in the early
rehabilitation (the tendency to significant differences
when t < 1.92 and p < 0.072). In the lower limbs, the
early rehabilitation did not affect the strength growth
dynamics in the 1st month but led to a better final
recovery (see Table 4). Comparison of the intensity
of restoration of arm and leg movements indicated that
in the 1st month, regardless of the rehabilitation start
time, leg movements restored significantly slower
compared to arm ones (p = 0.027). When analyzing
the Semax influence on the degree and dynamics of
reducing the paresis intensity, there were no
significant differences throughout the study between
the 1st and 2nd groups.
There were some interesting results after studying
of the effect of semax and BDNF level onto paresis
dynamics taking into account the rehabilitation start
time. The assessment was done in two stages. At the
first stage, the observation results of 1a subgroup
(early rehabilitation, semax is taken) and 2a subgroup
(late rehabilitation, semax is taken) were analyzed.
This option was due to the fact that the BDNF initial
and subsequent levels and dynamics throughout all
study between these subgroups were completely
comparable unlike the BDNF levels and dynamics
between 1b and 2b subgroups (see Table 3). Despite
of the same BDNF level and the semax is taken in both
subgroups, nevertheless there were found
outperforming results and the best final recovery (see
Table 4) in 1a subgroup (early rehabilitation). At the
second stage, a comparison was made of the 1b
subgroup with the 2a subgroup. Initially, the BDNF
level did not differ between these subgroups (see
Tables 1 & 3). By the 1st month end and by the study
end, the BDNF level and its increase were
significantly higher than in the 2a subgroup (t > 2.43;
p < 0.018). At the same time, the arm paresis decrease
rate by the 1st month end was significantly higher than
in the 1b subgroup (i = 2.67; p = 0.01). The derived
data can be interpreted as an evidence of the presence
of a more pronounced effect of very low BDNF
concentrations on recovery, in particular, on a paresis
decrease in the early period after AS. This peculiarity
is most likely associated with the plasticity dynamics
after focal brain damage and with the presence of an
optimal time interval in the early period for the action
by trophic factors including BDNF [3, 11].
Thus, the early rehabilitation start contributed to a
faster and more complete arm and leg paresis decrease
which is most likely due to the optimal, for the muscle
strength and simple movements’ restoration, state of
plasticity processes in the brain during this period.
The effect of the semax use and the rehabilitation start
time on the daily living activities

Table 4. Dynamics of muscle strength restoration of examined patients (M±m)

Total score Total score incremental growth (Δ)
Group
Initially 1 month later 5 months later Initially — 1 month later Initially — 5 months later
Upper limb
The 1st group
The 1a subgroup 3.1±0.18 4.2±0.24* 4.4±0.23* 1.10±0.21** 1.23±0.20#
The 1b subgroup 3.2±0.19 4.1±0.20* 4.1±0.24* 0.91±0.18*** 0.92±0.21
The 2nd group
The 2a subgroup 3.1±0.20 3.5±0.19 3.8±0.21* 0.39±0.19 0.72±0.21
The 2b subgroup 3.1±0.21 3.4±0.17 3.7±0.18* 0.26±0.18 0.55±0.19
Lower limb
The 1st group
The 1a subgroup 3.0±0.15 3.5±0.20* 4.5±0.25* 0.45±0.17 1.51±0.19##
The 1b subgroup 2.9±0.16 3.5±0.18* 4.5±0.23* 0.62±0.18 1.57±0.19##
The 2nd group
The 2a subgroup 3.3±0.11 3.7±0.17 4.5±0.26* 0.34±0.17 1.03±0.17
The 2b subgroup 3.0±0.16 3.5±0.18 3.7±0.20* 0.54±0.18 0.71±0.18

Note. * —differences are significant compared with the initial indicator when t≥2.01 and p≤0.05; ** — differences are significant between 1a and 2a subgroups when
t=2.51 and p=0.015; *** — differences are significant between 1b and 2b subgroups with t=2.41 and p=0.02; # — tendency to significant differences between 1a and 2a
subgroups when t=1.75 and p=0.081; ## — differences are significant between 1a and 2a and 1b and 2b subgroups when t≥2.99 and p≤0.005.

JOURNAL OF NEUROLOGY AND PSYCHIATRY, 3, 2018; Issue 2 65

 Table 5. The total score dynamics in the Barthel scale of the examined patients
Total score of the Barthel scale (M±m)
Group
Initially 1 month later
The 1st group
The 1a subgroup 58.2±2.1 80.4±2.6*
The 1b subgroup 58.8±2.0 70.2±2.1*
The 2nd group
The 2a subgroup 60.5±2.4 75.5±2.0*
The 2b subgroup 58.9±1.9 62.7±2.1
Note. * — differences are significant in groups between indicators when patients are started be involved, 1 and 5 months later when t>2.61; p<0.026; ** — differences
are significant between 1a and 1b subgroups when t=2.84 and p=0.006; *** — differences are significant between 2a and 2b subgroups when t=4.48 and p=0.000; # —
differences are significant between 2a and 2b subgroups when t=2.07 and p=0.044; ## — differences are significant between 1a and 2b subgroups when t=2.08 and
p=0.042; t — differences are significant between 1b and 2b subgroups when t=2.36 and p=0.022; tt — differences are significant between 1b and 2b subgroups when
t=2.39 and p=0.021.
Initially, the total score on the Barthel scale did not
differ between the groups (see Table 1). The total
score increase in 1a, 1b & 2a subgroups was
statistically significant (Table 5) 1 month after the
rehabilitation starting. By the 5th month end, a further
increase in the total score was observed and the growth
became statistically significant in all subgroups.
The semax taking influenced the growth of values
on the Barthel scale, significantly accelerating it in the
1st rehabilitation month. So, in 1a and 2a subgroups,
by the 1st month end of rehabilitation, the total score
increase was 78.5% and 62.4% of the total increase
while in 1b and 2b subgroups the increase was 43.8%
and 21.9% only. In addition, the semax taking resulted
in the total score increase on the Barthel scale in case
of the late rehabilitation (see Table 5).
When analyzing the semax effect on the dynamics
of individual sections of the Barthel scale, it was noted
that in the 1a subgroup the statistically significant
dynamics by the 1st month end was due to the score
increase related to movements criteria (the score in the
“climbing stairs” test increased by 46 %, “chair seat
changing” by 40%, “walking” by 80%) and due to
self-maintenance (“eating” + 54%, “bath taking” +
60%, “toileting” + 46%). There was the similar
dynamics in the 2a subgroup: the maximum increase
in indicators was registered in the sections such as
“climbing stairs” (+ 32%), “chair seat changing” (+
40%), “walking” (+ 77%), “eating” (+49 %) and
“toileting” (+ 38%).
Another important factor influenced, along with
the Semax use, on the dynamics of indicators on the
Barthel scale, was rehabilitation start time. The early
rehabilitation (1a & 1b subgroups) was evidenced with
the fast increase of the total score by the 1st month end
compared to the 2a and 2b subgroups, as well as with
the higher total increase in the 1b subgroup compared
to the 2b subgroup (see Table 5).
The total score on the Barthel scale correlated with
the BDNF level by both the 1st month end and by the
study end (r = 0.31 and r = 0.24, respectively; p <
0.017). This correlation was more pronounced during
the early rehabilitation compared to the late one (r =
0.37 and r = 0.21 respectively; p < 0.011), as well as
66
Barthel scale incremental growth (Δ) (M±m)
Initially — 1 month later — Initially —
5 months later
1 month later 5 months later 5 months later
85.8±2.3* 21.6±1.8**. ## 5.4±0.9 27.5±2.1
84.1±1.8* 11.3±1.7t 13.7±1.1 25.8±1.2tt
84.3±2.2* 14.8±1.4*** 8.9±1.0 23.7±1.3#
79.5±2.0* 4.1±0.7 16.7±1.2 18.7±1.4
towards the 1st month end compared with the end of
the study (r = 0.36 and r = 0.19 respectively; p <
0.047).
Thus, the semax taking in both the early and the
late rehabilitation significantly accelerated the growth
of indicators on the Barthel scale by the 1st month end,
and also contributed to better final recovery during the
late rehabilitation. There was a correlation between
the BDNF level and recovery on the Barthel scale
while the correlation was more significant during the
early rehabilitation, what indicates about the existence
of an optimal time period for BDNF action.
Conclusion
In this study was shown that combined use of both
the semax and the early IS rehabilitation has been
increasing the plasma BDNF level, decreasing the
limb paresis and restoring functional activity as to the
Barthel scale. The semax use had a major impact on
the BDNF level and its dynamics throughout the
observation period and, at the same time, leveled the
influence of the rehabilitation start time on BDNF
indicators. Patients taking semax had the BDNF level
was significantly higher throughout the study than
those patients who did not take it. With the semax
prescribed, there was a faster BDNF growth in the 1st
rehabilitation month, and the plasma BDNF level
remained stably high throughout the entire study
period and did not differ between the groups of the
early and the late rehabilitation. The rehabilitation
start time had an effect on BDNF levels only among
those patients who did not take semax. The early
rehabilitation patients had the significantly larger and
faster BDNF level increase compared to the late
rehabilitation patients. It is important to stress that the
high BDNF level did not always correlate with
restoration of motor functions, primarily of limbs’
paresis. And better and faster recovery with the same
or even lower BDNF level was achieved with the early
rehabilitation. This could be due to the fact that one of
the application points of BDNF are presynaptic and
postsynaptic dendritic receptors [24], which are most
JOURNAL OF NEUROLOGY AND PSYCHIATRY, 3, 2018; Issue 2
plastic in the first few weeks after focal brain damage associated not only with the plasma BDNF level increase
[25]. After this period, the action of trophic factors but also with its direct stimulation of the anterior parts of
even at high concentrations becomes less effective [11]. the cerebral hemispheres [18, 26] which improved the
Comparison of the effectiveness of the concentration of attention, perception of information and
rehabilitation start time and the semax use indicated involving into activities [29]. The long-term effect of
that the dynamics of both decreasing limbs’ paresis the medication which having been observed
and increasing muscle strength primarily depended onthroughout the entire study, could be due to a steady
the rehabilitation start time while recovery on the and prolonged increase in the plasma BDNF level
Barthel scale depended on the rehabilitation start time
which contributed to the improvement of plastic
to a lesser extent and was rather determined by the processes, including the differentiation of cellular
semax use. Semax significantly accelerated growth inelements [30, 31]. Thus, the semax action in the
respect to the Barthel scale, and also contributed to the
restoration of the complex movements and skills has
best final functional recovery during the late BDNF-mediated and BDNF-not-mediated effects.
rehabilitation. This may be due to the fact that an Semax taking neither caused side effects nor led to a
improvement on the Barthel scale requires not only adeterioration of somatic condition. The medication did
paresis intensity decrease but also an improvement of
not have the effect of exhaustion; its acceptability was
such integral elements of each complex action as considered as either very good or good by 95% of
attention, involvement into a task, sequence of actions,
patients.
and other functions that are affected by the semax use The study indicated the effectiveness of the
[26]. In all groups, the total score on the Barthel scale
combined use of both the semax and the early IS
positively correlated with the BDNF level what couldrehabilitation in the complex treatment after IS in
be due to the BDNF influence on both the spatial
order to reduce motor impairment, improve functional
orientation and the ability to concentrate attention
independence as to the Bartel scale and increase the
when performing complex tasks [27, 28]. A
particularly pronounced semax effect on the Barthel plasma BDNF content.
scale’s indicators was observed after the 1st course of its
use. The rapid development of the semax effect could be Authors declare no conflict of interest among them.

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