Effects of ganglioside GM1 on expression of KCC2 in hippocampus after hypoxic ischemic brain damage in neonatal rats

Abstract

Objective To evaluate the effects of ganglioside GM1 on hypoxic ischemic brain damage (HIBD) in neonatal rats and on the expression of potassium-chloride cotransporter 2 (KCC2) in hippocampus. Methods Seven-day-old Sprague-Dawley (SD) rats (n=72) were randomly divided into a sham group, an HIBD group and a ganglioside GM1 group. Each group was further divided into a 3 d subgroup and a 21 d subgroup according to the different detection index (n=12). Rat HIBD models were prepared according the Rice-Vannucci method. After HIBD, the ganglioside GM1 group was given ganglioside GM1 20 mg/(kg·d) by intraperitoneal injection for 3 d continuously. 2-, 3-, 5-triphenyltetrazolium chloride (TTC) was preformed to evaluate the area of cerebral infarction of HIBD in each 3 d subgroup. Spontaneous activity recorder was used to observe the locomotor activity of the rats in the 21 d subgroups. Morris water maze test was conducted for assessment of rats' learning and memory abilities in the 21 d subgroups. Western blot analysis was employed to determine the alterations in KCC2 expression in hippocampus in all the 3 d and 21 d subgroups. Results Compared with the HIBD group (28.6%±5.2%), the ratio of cerebral infarction volume in the ganglioside GM1 group (11.3%±2.4%) was significantly reduced (P<0.05). Compared with the HIBD group (289.6±61.3), the number of locomotor activities within 2 h in the ganglioside GM1 group (412.1±66.8) was significantly increased (P<0.05). Compared with the HIBD group, the escape latency was significantly reduced, but the percentage time of target quadrant and the number of crossing the platform were significantly increased in the ganglioside GM1 group (P<0.05). Three days and 21 days after HIBD, the expression of KCC2 in the ganglioside GM1 group was significantly higher than that in the HIBD group (P<0.05). Conclusion Ganglioside GM1 may have a significant protective effect on HIBD in neonatal rats, and its mechanism may be related to regulation of the expression of KCC2 in hippocampus. Key words: Ganglioside GM1; Hypoxic ischemic brain damage; Potassium-chloride cotransporter 2