Escape of intraluminal platelets into brain parenchyma after subarachnoid hemorrhage

Abstract

Platelet aggregates are present in parenchymal vessels as early as 10 minutes after experimental subarachnoid hemorrhage (SAH). Structural injury to parenchymal vessel walls and depletion of collagen-IV (the major protein of basal lamina) occur in a similar time frame. Since platelets upon activation release enzymes which can digest collagen-IV, we investigated the topographical relationship between platelet aggregates, endothelium, and basal lamina after SAH produced by endovascular perforation, using triple immunofluorescence and confocal microscopy with deconvolution. The location of platelet aggregates in relation to zymography-detected active collagenase was also examined. As reported previously, most cerebral vessels profiles contained platelets aggregates at 10 minutes after SAH. High-resolution three-dimensional image analysis placed many platelets at the ab-luminal (basal) side of endothelium at 10 minutes, and others either within the vascular basal lamina or in nearby parenchyma. By 24 hours post-hemorrhage, large numbers of platelets had entered the brain parenchyma. The vascular sites of platelet movement were devoid of endothelium and collagen IV. Collagenase activity colocalized with vascular platelet aggregates. Our data demonstrate that parenchymal entry of platelets into brain parenchyma begins within minutes after hemorrhage. Three-dimensional analysis suggests that platelet aggregates initiate or stimulate local disruption of endothelium and destruction of adjacent basal lamina after SAH.

Delayed neurological deterioration after subarachnoid haemorrhage

“…38,39 Similar processes occur in the intraparenchymal micro circulation. 40 Platelets have been shown to aggregate in parenchymal microvessels, forming microthrombi and extravasating into the brain parenchyma within 10 min of SAH, and persisting for up to 24 h. 41 This process was associ ated with breakdown of collagen IV in the blood vessel basal lamina, possibly mediated by platelet activation -a process that releases proteases that digest collagen IV, such as matrix metalloproteinase 9. Whether transient global ischaemia or the subarachnoid blood clot cause the microcirculatory changes after SAH is unclear, but transient global ischaemia causes similar pathology that has been termed the 'noreflow' phenomenon.…”

Acute ischaemia after subarachnoid haemorrhage, relationship with early brain injury and impact on outcome: a prospective quantitative MRI study

“…At the time of aneurysm rupture intracranial pressure becomes transiently elevated, exceeding mean arterial pressure, leading to low or absent intracranial blood flow and consequent hypoperfusion ischaemia 8–11. Additionally, endothelial collagen exposure that occurs after aneurysm rupture has been correlated with platelet activation, aggregation and microcirculatory thrombosis in animal models, suggesting another possible mechanism of ischaemia 12 13. Early platelet activation has also been documented in clinical studies of SAH and correlates with worse admission neurological function 14…”

Platelet-mediated changes to neuronal glutamate receptor expression at sites of microthrombosis following experimental subarachnoid hemorrhage

“…The mechanisms leading to platelet aggregation might impact glutamate receptor signaling, as platelets are thought to release glutamate as part of their cell-cell signaling 19 and have been shown to escape into the neuronal parenchyma after SAH. 7 Here, we hypothesized that microthrombi contribute to neuron dysfunction after SAH through local glutamate release during platelet aggregation. Through mechanisms of excitotoxicity or downregulation of glutamate receptors, we hypothesized that local, platelet-mediated glutamate release during microthrombus formation might impact neuronal signaling and survival, thereby contributing to secondary injury following SAH.…”