Role of vascular mitogens in subarachnoid hemorrhage-associated cerebral vasculopathy.
BACKGROUND
Cerebral vasculopathy may play an important role in the development of delayed cerebral ischemia following subarachnoid hemorrhage (SAH). Platelet-derived growth factor AB (PDGF-AB) and vascular endothelial growth factor (VEGF) released from blood clot may trigger vasculopathy in cerebral arteries. We compared arteriographic and histological response to injection of blood with PDGF-AB and VEGF in basilar artery over 3 days.


METHODS
A total of 55 male New Zealand white rabbits were used in this study. SAH was simulated by single injection of 1 ml of autologous blood, while 50 microg PDGF-AB, 100 microg VEGF, and 50 microg PDGF-AB/100 microg VEGF combined were given in autologous cerebrospinal fluid (CSF) into the cisterna magna. Eight rabbits served as controls, receiving arteriograms but no cisternal injections, and 13 rabbits received reinjections of CSF. Basilar artery diameter was measured arteriographically at baseline and 3 days after injection. Immunohistochemistry was performed to assess change in the basilar artery.


RESULTS
Control groups showed significantly less (p < 0.0002) basilar artery narrowing than all treatment groups. Proliferating cell nuclear antigen (PCNA) was not significant for treatment groups compared to CSF reinject control. PCNA was significantly different for the no puncture group compared to the CSF reinject control. Von Willebrand Factor staining may indicate endothelial proliferation in the adventitia of SAH, VEGF, and PDGFAB/ VEGF combined groups. PDGF labeling was abundant for SAH, PDGF-AB, and PGDF-AB/VEGF combined.


CONCLUSIONS
PDGF-AB/VEGF and VEGF cause narrowing of the basilar artery similar to cisternal blood clot at 3 days, and thus blood clot was not required to cause arteriographic changes consistent with cerebral vasculopathy.
Miller
Cheryl A
CA
Duke University, Durham, North Carolina, USA.
Lombard
Frederick W
FW
Wu
Ching-Tang
CT
Hubbard
Cory J
CJ
Silbajoris
Lydia
L
Borel
Cecil O
CO
Niklason
Laura E
LE
D000818:Animals; D001488:Basilar Artery / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology; D002455:Cell Division / Q000502:physiology; D002533:Cerebral Angiography; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000503:physiopathology; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000473:pathology / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*; D014655:Vascular Resistance / Q000502:physiology; D020301:Vasospasm, Intracranial / Q000473:pathology / Q000503:physiopathology*
D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A; C095477:platelet-derived growth factor AB