Acute Physiologic and Morphologic Assessment Following Subarachnoid Hemorrhage - Animal Models of Acute Neurological Injuries: Injury and Mechanistic Assessments - page 296

3.1. Cerebrovascular
Physiology

The vascular events following SAH have been the focus of clinical
and scientifi c investigation. The acute changes in vascular physiol-
ogy and morphology immediately following SAH are poorly
understood, and likely contribute to early fatality. Reduction in
CPP and CBF related to acute increases in ICP is theorized to
be the primary cause of acute brain injury following SAH ( 12 ).
A rapid peak in ICP occurs within 60 s of vessel rupture, and returns
quickly to a value at or near baseline, followed by a later more sus-
tained rise ( 4 ). It has been demonstrated, in animal models, that a
decrease in CBF to less than 40% of baseline at 60 min posthemor-
rhage is associated with 100% mortality, while animals with CBF
greater than 40% of baseline at 60 min had a survival rate of 81%
( 5 ). Contrary evidence has suggested the magnitude of CPP reduc-
tion after SAH to be insuffi cient to result in cerebral perfusion
arrest. Additionally, increased ICP or decreased CPP are not always
associated with poor neurologic outcomes following SAH ( 13 ),
and therefore cannot entirely account for acute ischemic damage.

3.2. Changes in
Vascular Morphology

Disruption of the microcirculation, at the capillary level, is the
result of increased blood viscosity ( 14 ), formation of microthrombi
( 15 ), adherence of platelet aggregates ( 11 ), and vessel wall injury.
Destruction of basal lamina components within cerebral microves-
sels, by collagenases and matrix metalloproteinases (MMPs), has
been demonstrated within 3 h ( 16 ). Friedrich et al. have recently
described endothelial damage and leakage of platelets into the brain
parenchyma as early as 10 min following SAH. They demonstrate
platelet aggregation and extravasation, at sites devoid of endothe-
lium and collagen IV, thought to be mediated by collagenases
released by activated platelets ( 17 ). Infl ammatory mediators, such
as intercellular adhesion molecules-1 (ICAM-1), vascular adhesion
molecule-1 (VCAM-1), and E-selectin contribute to accumulation
of neutrophils, monocytes, and lymphocytes at the endothelial
membrane within 24 h ( 18 ). These factors coalesce to result in the
loss of structural integrity, which can affect vascular tone, increase
intravascular pressure and permeability, leading to edema and
extravasation of erythrocytes ( 11, 19 )

Global parenchymal edema demonstrated by computed tomography
has been documented early in patients admitted with SAH ( 20 ).
Sudden rise in ICP and the presence of SAH have been shown to
cause endothelial dysfunction and disrupt interendothelial junc-
tions of the blood-arterial wall barrier. This disturbance in perme-
ability of major cerebral arteries ( 21 ) leads to vasogenic and,
secondarily, cytotoxic edema. Decreased tissue oxygenation leads
to increased blood-brain barrier (BBB) permeability by a progres-
sive loss of component antigens from the basal lamina and extracel-
lular matrix, as well as alterations in endothelial cell-cell and
cell-matrix interactions within the fi rst few hours of ischemia
( 22, 23 ). Extravasation of large proteins (300 kDa) across the BBB

3.3. Edema Formation