Role of ERK1/2 and vascular cell proliferation in cerebral vasospasm after experimental subarachnoid hemorrhage

• Published in: Acta neurochirurgica 2009-09, Vol.151 (9), p.1127-1134
• Main Authors: Chen, Duo, Chen, Jian-Jun, Yin, Qiang, Guan, Jun-Hong, Liu, Yun-Hui
• Format: Article
• Language: English
• Subjects: Animals; Basilar Artery - cytology; Basilar Artery - enzymology; Cell Proliferation; Disease Models, Animal; Enzyme Activation - physiology; Enzyme Inhibitors - pharmacology; Experimental Research; Flavonoids - pharmacology; Hypertrophy - drug therapy; Hypertrophy - enzymology; Hypertrophy - physiopathology; Interventional Radiology; Medicine; Medicine & Public Health; Microscopy, Electron; Minimally Invasive Surgery; Mitogen-Activated Protein Kinase 3 - metabolism; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - enzymology; Myocytes, Smooth Muscle - cytology; Myocytes, Smooth Muscle - enzymology; Neurology; Neuroradiology; Neurosurgery; Proliferating Cell Nuclear Antigen; Rabbits; Subarachnoid Hemorrhage - complications; Surgical Orthopedics; Up-Regulation - physiology; Vasospasm, Intracranial - drug therapy; Vasospasm, Intracranial - enzymology; Vasospasm, Intracranial - physiopathology
• ISSN: 0001-6268; 0942-0940
• DOI: 10.1007/s00701-009-0385-3

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