Acute alterations in microvascular basal lamina after subarachnoid hemorrhage.
OBJECTIVE
Aneurysmal subarachnoid hemorrhage (SAH) causes acute and delayed ischemic brain injuries. The mechanisms of acute ischemic injury following SAH are poorly understood, although an acute increase in microvascular permeability has been noted. The integrity of cerebral microvessels is maintained in part by components of basal lamina: collagen IV, elastin, lamina, and so forth. Destruction of basal lamina components by collagenases and matrix metalloproteinases (MMPs), especially MMP-9, has been known to occur in other ischemic models. The authors assessed the integrity of cerebral microvasculature after acute SAH by examining collagen IV and MMP-9 levels and collagenase activity in the microvessels.


METHODS
Subarachnoid hemorrhage was induced in rats through endovascular perforation of the intracranial bifurcation of the internal carotid artery. Animals were killed 10 minutes to 48 hours after SAH or sham operation (time-matched controls). Levels of collagen IV and MMP-9 were studied in the microvasculature by performing immunoperoxidase and immunofluorescence staining, and collagenase activity was assessed by in situ zymography. Little change occurred in collagen IV and MMP-9 immunostaining or collagenase activity at 10 minutes or 1 hour after SAH. Starting 3 hours after SAH, collagen IV immunostaining was reduced or eliminated along segments of microvessels whereas MMP-9 staining was segmentally increased. These effects reached a maximum at 6 hours and returned toward those values in sham-operated controls at 48 hours.


CONCLUSIONS
Results of this study demonstrated an acute loss of collagen IV from the cerebral microvasculature after SAH and indicated that MMP-9 contributes to this event. The loss of collagen IV might contribute to the known failure of the blood-brain barrier after SAH.
Departments of Neurosurgery and Neurobiology, Mount Sinai School of Medicine, New York, New York 10029-6574, USA. fatima.sehba@mssm.edu
Fatima A
FA
Sehba
Gulam
G
Mostafa
Jared
J
Knopman
Victor
V
Friedrich
Joshua B
JB
Bederson
D000208:Acute Disease; D000818:Animals; D001485:Basement Membrane / Q000098:blood supply* / Q000473:pathology*; D002545:Brain Ischemia / Q000209:etiology*; D024141:Collagen Type IV / Q000032:analysis; D004195:Disease Models, Animal; D002532:Intracranial Aneurysm / Q000150:complications*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D008833:Microcirculation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000150:complications*
D024141:Collagen Type IV; D020780:Matrix Metalloproteinase 9