Crotalus helleri venom preconditioning reduces postoperative cerebral edema and improves neurological outcomes after surgical brain injury

响尾蛇毒液预处理可减少术后脑水肿并改善手术脑损伤后的神经系统结果

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作者:Cherine H Kim, Devin W McBride, Prativa Sherchan, Carl E Person, Eric C K Gren, Wayne Kelln, Tim Lekic, William K Hayes, Jiping Tang, John H Zhang

Conclusion

Our findings indicate that Cv-PC may provide a promising therapy for reducing postoperative edema and improving neurological function after neurosurgical procedures.

Methods

75 male Sprague Dawley rats (280-330g) were divided to the following groups-naïve+vehicle, naïve+Cv-PC, sham, vehicle, Cv-PC, Cv-PC+NS398 (COX-2 inhibitor). Vehicle preconditioned and Cv-PC animals received either three daily subcutaneous doses of saline or C. helleri venom at 72h, 48h, and 24h prior to surgery. In Cv-PC+NS398 animals, NS398 was administered intraperitoneally 1h prior to each Cv-PC injection. Sham-operated animals received craniotomy only, whereas SBI animals received a partial right frontal lobectomy. Neurological testing and brain water content were assessed at 24h and 72h after SBI; COX-2 and PGE2 expression was assessed at 24h postoperatively by Western blot and immunohistochemistry, respectively.

Results

At 24h after SBI, the vehicle-treated animals were observed to have increased brain water content (83.1±0.2%) compared to that of sham animals (80.2±0.1%). The brain water content of vehicle-treated animals at 72h post-SBI was elevated at 83.3±0.2%. Cv-PC-treated animals with doses of 10% LD50 had significantly reduced brain water content of 81.92±0.7% and 81.82±0.3% at 24h and 72h, respectively, after SBI compared to that of vehicle-treated animals, while Cv-PC with 5% LD50 doses showed brain water content that trended lower but did not reach statistical significance. At 24h and 72h post-SBI, Cv-PC-treated animals had significantly higher neurological score than vehicle-treated animals. The COX-2 over-expression characterized in SBI was attenuated in Cv-PC-treated animals; NS398 reversed the protective effect of Cv-PC on COX-2 expression. Cv-PC tempered the over-expression of the inflammatory marker PGE2.

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