The protective effect of hypoxia preconditioning on epilepsy induced by lithium-pilocarpine in rats

Abstract

Objective To investigate the brain protection of intermittent hypoxia preconditioning (IHP) on rats with seizures induced by lithium-pilocarpine (Li-pilo). Methods 96 rats were randomly divided into control group, seizure group and four IHP-seizure group. The animal model of epilepsy was established by Li-pilo intraperitoneal injection in seizure group and four IHP-seizure groups (Li-pilo was injected 1, 3, 7, or 14 days after a 5-day regimen of IHP). Subsequently, 240 min video data of seizure behavior was tested, histological grade (HG) and neuronal density (ND) in rat hippocampal CA1 subfield via terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labeling (TUNEL) and Nissl’s staining. Results Modified Racine scales of induced seizure peaked on average between 50-150 min after Li-pilo administration. The average peak score in IHP-3 d seizure group [(1.42±0.50) points, P=0.007] was significantly lower than seizure group [(4.15±0.72) points] and IHP-1 d [(2.16±0.69) points, P=0.028]; 7 d [(2.26±0.53) points, P=0.030] seizure group. The average escape latency in seizure rats [(54.33±3.90) s was significantly longer than Control group [(36.95±15.71) s, P=0.011], IHP-1 d seizure group [(44.83±11.68) s, P=0.047], IHP-3 d seizure group [(38.75±15.32) s, P=0.012] and IHP-7 d seizure group [(44.73±11.18) s, P=0.045]. The neuronal apoptosis rate and HG in seizure group were also higher than the other groups. The average percentage of time in the probe quadrant and ND value in seizure rats [(29.63±4.95)%; (35.25±8.37) cells/HP] were obviously lower than Control group [(41.13±19.09)%, P=0.013; (110.35±9.87) cells/HP, P=0.000], IHP-1 d seizure group [(36.13±13.97)%, P=0.037; (65.31±7.25) cells/HP, P=0.007], IHP-3 d seizure group [(42.38±20.15)%, P=0.011; (98.50±14.20) cells/HP, P=0.000] and IHP-7 d seizure group [(33.94±8.75)%, P=0.040; (54.80±11.68) cells/HP, P=0.010]. Conclusion The results indicate that 5-day IHP manipulation can afford definite anti-epileptic functions to epileptic model rats. Key words: Hypoxia preconditioning; Epilepsy; Apoptosis; Neuroprotection; Rat