Protective effect of topiramate on hypoxic-ischemic brain injury in neonatal rat

Abstract

Objective: To explore protective effect of topiramate (TPM) on hypoxic-ischemic brain injury.

Methods: A total of 360 neonatal rats were selected then randomly divided into sham operation group, ischemia and hypoxia group, conventional treatment group and degradation therapy group (n=90). After surgical treatment, sham and ischemic hypoxia group were treat with normal saline; conventional treatment group was received TPM solution 100 mg/kg, 2 times/d; degradation therapy group received TPM solution 150 mg/kg, 2 times/d, per 3 d treatment each dosage was reduced 50 mg/kg, the lowest reduced to 50 mg/kg. Four groups received continuous treatment for 10 d. After treatment for 1 d, 4 d, 7 d, 10 d the cerebral edema, neuron-specific enolase (NSE) and γ-aminobutyric acid (GABA) levels and cognitive abilities of four groups were observed.

Results: After 1 d, 4 d of treatment, the brain water content and NSE levels in ischemia and hypoxia group, the conventional treatment group and the degradation therapy group were significantly higher than that in sham group (P<0.05), the brain water content and NSE levels of the conventional treatment group and the degradation therapy group were significantly lower than that in the ischemic hypoxia group (P<0.05). GABA levels and learning ability of the ischemia and hypoxia group, the conventional treatment group and degradation therapy group were significantly lower than the sham group (P<0.05), the GABA levels and learning ability of the conventional treatment group and degradation therapy group were significantly higher than the ischemia and hypoxia group (P<0.05). After 7 d, 10 d of treatment, the brain water content and NSE levels in the sham operation group, the conventional treatment group and degradation therapy group were significantly lower than the ischemia and hypoxia group (P<0.05), while the GABA levels and learning ability of these three groups were significantly higher than that in the ischemia and hypoxia group (P<0.05), the GABA levels in the conventional treatment group were significantly higher than degradation therapy group (P<0.05); After 10 d of treatment, the GABA levels of the conventional treatment group were significantly higher than the sham group, the learning ability of the degradation therapy group and sham operation group were significantly higher than the conventional treatment group (P<0.05).

Conclusions: The correct amount of short-term TPM has protective effect on hypoxic-ischemic brain injury, but long-term or excessive use may cause new damage to the brain and reduce the cognitive ability.

Keywords: Brain Injury; GABA; NSE; TPM.