Recurrent neonatal seizure induced behavioral changes and the intervention by cathepsin B inhibitor

Abstract

Objective To explore the intervention effect of cathepsin B inhibitor (CBI) and its signaling pathways after flurothyl inducing brain injury in rats with recurrent seizures. Methods 6-day-old (P6) SD rats were randomly divided into: recurrent neonatal seizure group ( RS group, n = 30), CBI-treated seizure group ( CBI group, n=30) and the control group( CONT group). Rats in RS group were subjected to 5 seizures with flurothyl during the first 14 days of life. In CBI group,CBI was injected each day before seizures were induced. Then examined development indexes such as the physical growth, neural reflex, neural behavior and cognitive emotional competence. Western blot was employed to determine Cathepsin B expression at different time points ( 1.5h,3h,6h,24h and P35) after the last convulsion. Results The weights of rats in RS group( (27.28 ± 1.6) kg) were lighter than CONT group( ( 33.45 ± 1.57 ) kg). They had significant difference (P＜ 0.01 ) at the age of p14. The time of cliff avoidance in RS group( (2. 10 ± 1.45 ) s) was longer than CBI group( ( 1.05 ± 0. 32) s). It showed a statistically significant (P ＜ 0.05 ) in p12. In the open-field behavior test: the activities of RS group (20.00 ± 13.08 )were markedly reduced than CONT group ( 57.83 ± 33.22 ) in the horizontal movements, the RS group ( 2.50 ±2.43 ) were significantly decreased than the CONT group and CB1 group( ( 22.17 ± 10.74), (9.33 ± 5.39 ) ) in the vertical motions (P ＜ 0. 05 ). Cathepsin-B expression in RS group( 1.5h, 3h,6h and 24h )was significantly higher than that at the same time in CONT group(P＜ 0. 05 ). Cathepsin-B expression of CBI group was significantly decreased compared with that in RS group (P＜ 0. 05 ) at the time point (1.5h ,3h,6h and 24h). There were no significant differences among three groups at P35(P＞0.05 ). Conclusions CBI can improve brain injury and regulate the expression of abnormal molecules. Key words: Seizure; Neonatal; Physical growth; Open-field; Cathepsin-B inhibitor