Deneysel Kafa Travması Modelinde Intraventriküler Antisens Oligonükleotid Injeksiyonu ile Aquaporin-4 Ün Baskılanmasının Beyin Ödemi Üzerine Etkisi

Abstract

Objective: Aquaporin-4 (AQP4) plays an important role in the regulation of water balance in the brain. In this study, inhibition of AQP4 synthesis and decrease in brain edema following intraventricular injection of antisense oligonucleotide after focal cortical contusion injury in mice are investigated. Methods: 12-week, female Swiss albino mice of 20-25 g weight, were used to create focal cortical contusion model by the weight drop method (35 grams blunt weight, 70 cm height) onto parietal cortex after craniectomy. In the sham group, only craniectomy was performed (no trauma) (5 animals). In the control group, weight was dropped onto parietal cortex immediately after 2μl Dulbecco's Modified Eagle Medium (DMEM) was injected intracerebroventricularly (i.c.v.) following craniectomy (6 animals). 1 nM of aquaporin-4 antisense oligonucleotide was dissolved in 2μl DMEM and injected via intracerebroventricular (i.c.v) route immediately before trauma (minute 0) and at 4 hours after trauma (6 animals per group). All animals underwent MR imaging and were sacrificed at 24 hours after trauma. Percent brain water content was determined using the wet/dry weight method. Results: In the sham group, the average percent brain water content was 77.75%, while it was 79.87% in the control trauma group. The difference between two groups was statistically significant (p=0.017). In the zero-minute AQP-4 antisense therapy group, average brain water content was 78.81% and significantly reduced in comparison to the control trauma group (p=0.026). In the fourth-hour AQP-4 antisense therapy group, the average brain water content was 79.11%, and the difference between this group and the control trauma group was not statistically significant (p=0.39). MR imaging findings also showed significant reduction in brain edema in the zero-minute treatment group. However, the results of the fourth-hour treatment group, when compared with the control trauma group, did not show a significant difference. vi Conclusion: The results of this study demonstrated that AQP-4 antisense oligonucleotide therapy, when administered early after diffuse traumatic brain injury, leads to the significant reduction in brain edema.