Vasospasm and p53-induced apoptosis in an experimental model of subarachnoid hemorrhage.
OBJECTIVE
Despite intensive research efforts, the etiology of vasospasm (sustained constriction of the cerebral vessels) remains unknown. In this study, we investigated the role of p53-induced apoptosis in the vasculature at 24 and 72 hours. To completely examine the apoptotic cascades, key proteins of the caspase-dependent, -independent and mitochondrial pathways were examined.


METHODS
In this study, adult rats were divided into 3 groups: sham (n=21), nontreatment (subarachnoid hemorrhage [SAH]+dimethyl sulfoxide; n=42), and treatment (SAH+pifithrin-alpha) (n=42) groups. Each animal in the SAH group underwent a surgical procedure to induce SAH, and the basilar artery was harvested at 24 and 72 hours for analysis.


RESULTS
We found severe vasospasm at the 24-hour time point, which persisted to 72 hours. Furthermore, we found that the markers of the apoptotic cascades rose significantly at the 24-hour time point but had dissipated by 72 hours. However, the neurological outcome and mortality scores improved at the 72-hour time point.


CONCLUSIONS
Apoptosis, and in particular p53, may play an important role in the etiology of vasospasm with relation to SAH, and in this model, vasospasm persisted to 72 hours, despite the fact that apoptosis does not.
Cahill
Julian
J
Department of Physiology, Loma Linda University Medical School, Loma Linda, Calif, USA.
Calvert
John W
JW
Solaroglu
Ihsan
I
Zhang
John H
JH
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics; D001488:Basilar Artery / Q000473:pathology; D052160:Benzothiazoles; D001812:Blood-Brain Barrier; D015153:Blotting, Western; D001834:Body Water; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D002560:Cerebrovascular Circulation; D008297:Male; D023421:Models, Animal; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D010539:Permeability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016037:Single-Blind Method; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy / Q000473:pathology*; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use; D014050:Toluene / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000502:physiology*; D020301:Vasospasm, Intracranial / Q000209:etiology / Q000473:pathology*
D051017:Apoptosis Regulatory Proteins; D052160:Benzothiazoles; D009419:Nerve Tissue Proteins; D013844:Thiazoles; D016159:Tumor Suppressor Protein p53; D014050:Toluene; C121565:pifithrin