Potential role of Ras in cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits.
Previous studies have demonstrated that mitogen-activated protein kinase (MAPK) is involved in the pathogenesis of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). Ras, an upstream regulator of MAPK, may be activated following SAH. The aim of this study was to investigate the role of Ras in cerebral vasospasm in a rabbit model of SAH. We first investigated the time course of Ras and ERK1/2 activation in the basilar artery after SAH. Next, for the time point at which Ras was maximally activated, we assessed the effect of FTI-277 (a Ras farnesyltransferase inhibitor) on cerebral vasospasm. SAH was induced by injecting autologous blood into the cisterna magna on both day 0 and day 2. FTI-277 was injected into the cisterna magna every 24 hours, beginning 30 minutes after blood injection to the last day of the experiment. Elevated expression of Ras-GTP and phosphorylated ERK1/2 was detected in the basilar artery after SAH and expression peaked on day 3. FTI-277 administration resulted in lower Ras-GTP and phosphorylated ERK1/2 levels and markedly attenuated vasospasm in the basilar arteries relative to animals that did not receive FTI-277. Our results suggest that Ras protein is activated in the arterial wall after SAH and contributes to vasospasm development.
Zhao
Xu Dong
XD
Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, China.
Zhou
Yi Ting
YT
Wu
Yi
Y
Zhuang
Zong
Z
Huang
Ren Qiang
RQ
Song
Zhi Jun
ZJ
Yin
Hong Xia
HX
Shi
Ji Xin
JX
D000818:Animals; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008715:Methionine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D011817:Rabbits; D011897:Random Allocation; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000201:enzymology / Q000378:metabolism*; D020301:Vasospasm, Intracranial / Q000201:enzymology / Q000209:etiology / Q000378:metabolism*; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*
D004791:Enzyme Inhibitors; C096856:FTI 277; D008715:Methionine; D018631:ras Proteins