Atorvastatin ameliorates cerebral vasospasm and early brain injury after subarachnoid hemorrhage and inhibits caspase-dependent apoptosis pathway.
BACKGROUND
Cerebral vasospasm (CVS) and early brain injury remain major causes of morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). Hydroxymethylglutaryl coenzyme A reductase inhibitors, also known as statins, has the neuroprotective effects and ameliorating CVS after SAH. This study was designed to explore apoptosis inhibiting effects of atorvastatin and its potential apoptotic signal pathway after SAH.


RESULTS
Preserving blood-brain-barrier permeability, decreasing brain edema, increasing neurological scores and ameliorating cerebral vasospasm were obtained after prophylactic use of atorvastatin. TUNEL-positive cells were reduced markedly both in basilar artery and in brain cortex by atorvastatin. Apoptosis-related proteins P53, AIF and Cytochrome C were up-regulated after SAH, while they were not affected by atorvastatin. In addition, up-regulation of caspase-3 and caspase-8 after SAH was decreased by atorvastatin treatment both in mRNA and in protein levels.


CONCLUSIONS
The neuroprotective effects of atorvastatin after SAH may be related to its inhibition of caspase-dependent proapoptotic pathway based on the present results.
Cheng
Gao
G
Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Nangang District, Harbin, Heilongjiang, PR China. doctorgaocheng@yahoo.com.cn
Wei
Liu
L
Zhi-Dan
Sun
S
Shi-Guang
Zhao
Z
Xiang-Zhen
Liu
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000069059:Atorvastatin; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D001929:Brain Edema / Q000188:drug therapy; D001930:Brain Injuries / Q000188:drug therapy* / Q000209:etiology; D020169:Caspases / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D006538:Heptanoic Acids / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000503:physiopathology*; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000209:etiology; D014867:Water / Q000378:metabolism
D006538:Heptanoic Acids; D018696:Neuroprotective Agents; D011758:Pyrroles; D012333:RNA, Messenger; D014867:Water; D000069059:Atorvastatin; D020169:Caspases