title: Role of ERK1/2 and vascular cell proliferation in cerebral vasospasm after experimental subarachnoid hemorrhage.
abstract: 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.
authors.affiliation: Department of Neurosurgery, The Affiliated Shengjing Hospital of China Medical University, Shenyang, China. chenduo65@yahoo.com.cn
authors.forename: Duo
authors.initials: D
authors.lastname: Chen
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Chen
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yin
authors.forename: Jun-Hong
authors.initials: JH
authors.lastname: Guan
authors.forename: Yun-Hui
authors.initials: YH
authors.lastname: Liu
mesh_terms: 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
chemical_list: 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