Purpose: Traumatic brain injury (TBI) leads to important and deleterious neuroinflammation, as evidenced by edema, cytokine production, induction of nitric oxide synthase, and leukocyte infiltration. Strategies that block inflammatory and oxidative mediators have been shown to induce neuroprotective and anti-inflammatory effects after brain injury. After TBI, cerebral vascular endothelial cells play a crucial role in the pathogenesis of inflammation. In this study, we hypothesized that cerebral vascular endothelial cells play a crucial role in the pathogenesis of inflammation after TBI and, in conjunction with leukocytes, represent a key cellular target for statin therapy. We investigated the effect of acute and continuous treatment of simvastatin on behavior and inflammation in adult rats following experimental TBI.
Materials and Methods: Cortical contusions were induced using a device adapted from the impact method. There were 3 groups: (1) sham group, craniotomy only; (2) control group, TBI without treatment; and (3) treatment group, TBI with simvastatin administration. The treatment group received 15 mg/kg of simvastatin daily for 3 days. Neurological function was assessed with the grip test (Grip strength meter, Singa).
Results: Non-treatment control group had a significantly greater increase in ICAM-1 expression from pre-injury to the post-injury 72 h time point, compared to the simvastatin treatment group. The treatment group had a significantly smaller amount of reduction in successful trials in grip test than the control group did from baseline to 72 h. The analysis of western blot and pathological study also demonstrated similar results.
Conclusion: Our findings indicate that continuous administration of simvastatin after injury attenuates the cerebral vascular endothelial inflammatory response and improves functional and histological outcomes in a rat model of TBI. This improvement is associated with a reduction in expression of ICAM-1 in the blood and brain after rat TBI when compared with the untreated control group. Hence, we recommend simvastatin administration in the first 72 h following TBI.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0818111-155727 |
| Date | 18 August 2011 |
| Creators | Wang, Kuo-wei |
| Contributors | Char-Neng Tseng, Chung-Lung Cho, Han-Jung Chen |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0818111-155727 |
| Rights | unrestricted, Copyright information available at source archive |
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