| Objective: To explore the neurovascular protective effect of fasudil and its mechanism after subarachnoid hemorrhage through inducing subarachnoid hemorrhage model of rat.Methods: Forty-eight rats were randomly divided into three groups: control group, SAH group and fasudil-treatment group. Subarachnoid hemorrhage model was induced by single injection of blood into cisterna magna of rats. Rats were killed at 1, 3, 7, 14d after modeling and brains of rats were removed and sliced. Sections were stained with hematoxylin and eosin for microscopy. The morphological change of basilar artery and neurons of hippocampus were observed by light microscopy. The diameter and wall thickness of basilar artery were measured and the neuron density of CA1 region of hippocampus was calculated. The eNOS expression in basilar artery and immunoreactivity of albumin and MPO in brain sections were detected by immunohistochemical SP method.Results: 1. The vasospasm of basilar artery of rat in SAH group occurred at 1d after modeling, peaked at 3d, and mitigated at 7d. Fasudil attenuated the vasospasm of basilar artery with the diameter and wall thickness of basilar artery of fasudil-treatment group being statistically different from that of SAH group at 3d (P<0.05). 2. The amount of normal neurons in CA1 region of hippocampus of rat in SAH group was decreased obviously at 1, 3, 7 and 14d after modeling and the majority of neurons showed degenerative appearance. The pathological changes of neurons in the hippocampal CA1 region of fasudil-treatment group was palliated on 3, 7,14d after modeling, the neuron density of fasudil-treatment group was statistically different from that of SAH group(P<0.05). 3. Cells expressing MPO mainly distributed around the vessels that pass through subarachnoid space and were barely observed in parenchyma of brain. The amount of cell-MPO positive at 3d in each group was significantly reduced compared with that at 1d (P<0.05). There were few cells expressing MPO at 7 and 14d after modeling. The amount of cell-MPO positive in fasudil-treatment group was significantly decreased compared with that of SAH group at either 1 or 3d after modeling (P<0.05). 4. The expression of eNOS in basilar artery of rat in SAH group decreased significantly at 1, 3, 7 and 14d after modeling while the expression of eNOS in basilar artery in fasudil-treatment group increased at 3, 7 and 14d after modeling compared with SAH group, with statistical differences between the two groups at these time points (P<0.05). 5. The expression of albumin in brain section of rat in SAH group increased at 1d after modeling, peaked at 3d, and decreased at 7d. The expression of albumin in fasudil-treatment group decreased at 3d after modeling and the mean optical density of fasudil-treatment group was statistically different from that of SAH group at this time point(P<0.05).Conclusion: 1.Fasudil can effectively attenuate the cerebral vasospasm. Increased the expression of eNOS in artery wall by fasudil may play an important role in effect of anti-vasospasm of fasudil. 2. There may be no apparent role for neutrophil infiltration in delayed cerebral vasospasm. 3. Fasudil can effectively decrease the permeability of blood-brain barrier. 4. Fasudil exerts its neural protective effect via attenuating of cerebral vasospasm to increase cerebral blood flow and decreasing the permeability of blood-brain barrier. |
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