Hypoxic and Ischemic Encephalopathy- Pathology of Stroke

 Brain is sensitive because it works by oxidative phosphorylation

 Brain has no energy stores and most injury is caused by hypoperfusion
 Causes of energy shortage: ischemia, cerebral perfusion, hypoxia, hypoglycemia,
and anemia
 Usually is from cardiac arrest or shock (severe hypotension)
 Traumatic brain injury or increased intracranial pressure is a cause of HIE in adults
and children
 A rise of 10 mmHg (systolic) in the brain will cause brain capillaries to collapse
 There is a pump in the membrane of neurons that works against the concentration
gradients that is the source of neuronal membrane excitability (Na in and K out)
o In energy failure there is a depolarization of the membranes (fainting)
o If energy failure persists then there will be permanent neuronal damage
o Glu is dumped into the synaptic cleft (at toxic levels)
o Na channels open which causes a mass influx into the cell which results in
cellular edema
o Ca also rushes in and there is activation of cytolytic enzymes and other free
radicals which results in cell death
o Damage- energy failure, glutamate, mitochondrial injury free radicals, lactic
acidosis, edema
o Reperfusion, while maintaining brain function, allows the aforementioned
damages to occur as well
 Neurons are more sensitive than glial cells to damage because neurons have higher
energy demands
o Some neurons are more vulnerable- hippocampus, 3-5 cortical layers, purkinje
cells, and striatal cells
 Pathological Patterns of HIE
o Hippocampal sclerosis
 Patients with epilepsy or after cardiac arrest
 Purkinje cell sparing without hypoglycemia
 Segment of pyramidal layers are missing
 Causes Korsakoff amnesia- loss of episodic memory (long/short are
preserved)
o Laminal Cortical Necrosis (Pseudolaminar necrosis) and Thalamic injury 
Korsakoff (due to dorsal nu of thal involvement) or PVS – state when
wakefulness may be present but awareness is not; Diffuse cortical, thalamic, or
combined neuronal loss/white matter damage (with intact brainstem) –
bilateral
o Border zone (watershed) lesions- does not affect hippocampus
o Total Cerebral and Brainstem Damage
 Unresponsiveness, absent brainstem reflexes, no spontaneous respiration,
flat EEG, no circ, non perfused brain
 Imaging shows hypodesnity due to disintegration
 Cerebral infarcts involving brainstem
 Cerebrovascular Accident
o Cerebral Infarct- atherosclerosis, small vessel disease (HTN), emoblism
 Evolution: (1) Cerebral Necrosis (2) Edema (3) Caviation (months)
 Micro: (1) inflammation and axonal swelling (AA and FA) (2)
neovascularization at 2 weeks; monocytes enter the infarct and disgest
neurons and turn into lipid laden macrophages (3) macrophage reaction at 3-
4 weeks (4) gemistocytic astrocytes and glial scare (2 months)
 Embolic infarcts can look hemorrhagic but their primary process is an infarct
(clot lyses and then causes bleeding)
 Lacunar infarcts from small vessel disease (HTN/diabetes)can cause cystic
problems; affects deeper nuclei (basal ganglia/thalamus); can be just as bad
as more massive infarcts
 Cerebral Autosomal Dominant Arteriopathy with subcortial infarcts and
ischemic encephalopathy (CADASIL = notch 3 gene), coll 4A1 defects,
cerebral amyloid angiopathy
 Vascular dementia (multi-infarct)
 Ischemic penumbra- central zone where the necrosis/death is irreversible;
surrounded by a gray zone where recovery may be possible (this
surrounding zone is the penumbra)
o Cerebral Hemorrhage- HTN, arterial aneurysms, AVM, Angiopathy, Coagulopathy
 Caused by small vessel disease- vessels lose elasticity so their strength is
greatly diminished since strength is due to elasticity not stiffness
 Affects basal ganglia, thalamus, and lateral ventricles; also pons, cerebellum,
and central white matter
 Vascular lesions can cause infarction and hemorrhage
 Intracranial Aneurysm (Saccular/Berry Aneurysms)- located at the junction
of bifurcation of vessels
 Can enlarge and cause tumor like symptoms
 Can rupture (BAD)  Subarachnoid hemorrhage will cause increase in
intracranial pressure
 Risks – polycystic Kidneys, coarc, and female
 AVM- tangle of veins and arteries that are delicate and can hemorrhage and
cause seizures/focal defecits
 Cerebral Amyloid Angiopathy- parenchymal brain damage; amyloid/fibring
deposit in walls of arteries and makes them fragile
o
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