Role of ERK1/2 and vascular cell proliferation in cerebral vasospasm after experimental subarachnoid hemorrhage.
BACKGROUND
Although there are still some unresolved aspects, current research has revealed that vascular cell proliferation probably plays an important part in the pathological formation process of cerebral vasospasm. Using a "two-hemorrhage" model of subarachnoid hemorrhage (SAH), this study investigated the function of ERK1/2 and vascular wall cell proliferation in pathological development of cerebral vasospasm.


METHODS
Fifty rabbits were randomly divided into five groups: (1) SAH day 1, (2) SAH day 3, (3) SAH day 7, (4) SAH + DMSO (dimethyl sufoxide) solution, (5) SAH + PD98059 (a mitogen-activated protein kinase inhibitor) dissolved in DMSO solution. In the SAH + PD98059/DMSO group and SAH + DMSO control group, PD98059 in DMSO (2 mmol/l) or an equal quantity of DMSO, respectively, was injected into the cisterna magna, once a day from SAH day 1 to day 3. Western protein blotting was used to detect the expression of proliferating cell nuclear antigen (PCNA) and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in each group's basilar arteries. Light microscopy and electron microscopy were used for dynamic histological detection at each observation point of the SAH vascular wall under the effects of SAH and the mitogen-activated protein kinase inhibitor. Another 18 rabbits were randomly divided into three groups: SAH, SAH + DMSO and SAH + PD98059/DMSO; cerebral angiograpathy was conducted on SAH days 1 and 7, and the progression of angiographic vasospasm evaluated.


RESULTS
Compared with the control group, the extent of vasospasm after SAH increased with time. PD98059 significantly reduced angiographic and morphological vasospasm. In cerebral vasospasm, the expression of T-ERK1/2 showed no significant change. However, expression of p-ERK1/2 and PCNA began to increase significantly on day 3, and achieved a peak on day 7. PD98059 significantly inhibited the expression of p-ERK1/2 and PCNA (p < 0.05).


CONCLUSIONS
Cell proliferation on the vascular wall plays an important part in the pathological formation process of cerebral vasospasm. ERK1/2 phosphorylation, as an important signaling pathway, taking part in the process of vascular-wall pathological proliferation of cerebral vasospasm.
Chen
Duo
D
Department of Neurosurgery, The Affiliated Shengjing Hospital of China Medical University, Shenyang, China. chenduo65@yahoo.com.cn
Chen
Jian-Jun
JJ
Yin
Qiang
Q
Guan
Jun-Hong
JH
Liu
Yun-Hui
YH
D000818:Animals; D001488:Basilar Artery / Q000166:cytology / Q000201:enzymology; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006984:Hypertrophy / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D008854:Microscopy, Electron; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000201:enzymology; D018809:Proliferating Cell Nuclear Antigen; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D015854:Up-Regulation / Q000502:physiology; D020301:Vasospasm, Intracranial / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology
D004791:Enzyme Inhibitors; D005419:Flavonoids; D018809:Proliferating Cell Nuclear Antigen; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one