Effect of cog1410 on brain edema around lesion foci of mice with traumatic brain injury

Abstract

Objective To investigate the effect of cog1410 on brain edema around lesion foci after traumatic brain edema (TBI) in mice and possible mechanism. Methods APOE-knockout TBI mice (n=130) were divided into cog1410 group and saline group according to the random number table, with 65 mice per group. Several time points (0, 1, 3, 5, and 7 days) after TBI, 13 mice were sacrificed in each group. TBI was induced with controlled cortex injury to the mice. A single injection of cog1410 solution or saline was administered via the caudal vein in 30 minutes after TBI. Levels of aquaporin-4 (AQP-4) around the lesion tissues were measured using the Western blot and q-PCR methods. Brain water content was determined by the dry-wet weight method. Results Brain water content in cog1410 group and saline group increased after TBI, reached the peak at day 3 [(81.184±0.009)%vs (84.184±0.014)%] and normalized at day 7[(76.018±0.003)% vs (77.790±0.012)%]( P<0.05 ). There were almost no changes in AQP-4 mRNA expression in saline group after TBI. Whereas in cog1410 group, AQP-4 mRNA was greatly down-regulated at day 3 (0.278±0.014), increased greatly at days 5 and 7 after TBI (1.744±0.014, 1.782±0.003) ( P<0.05 ). Level of AQP-4 protein in saline group was increased at day 1 (0.491±0.060), reached the peak (0.605±0.099), and gradually returned to the preinjury level at days 5 and 7 (0.434±0.042, 0.358±0.034). By contrast, level of AQP-4 protein in cog1410 group revealed no notable changes at day 1, slight increase at day 3, significant increase at day 5 (1.079±0.090), and a peak at day 7 (1.247±0.210) (P<0. 05). Conclusion cog1410 can significantly alleviate brain edema around the lesion foci of mice with TBI, as may be achieved by altering the mRNA and protein levels of AQP-4. Key words: Craniocerebral trauma; Brain edema; Aquaporin 4