Systematic review and meta-analysis of the efficacy of different exercise programs in pilocarpine induced status epilepticus models

Abstract Purpose To conduct a systematic review and meta-analysis of studies testing exercise in animal models of pilocarpine induced status epilepticus (SE) and to compare the efficacy of different training strategies used in those studies. Methods We searched 2 online databases (Pubmed and Web of Science) for studies analyzing the efficacy of different trainings in pilocarpine-induced SE models. Training was categorized into forced physical training (PT), voluntary PT and resistance PT. Two reviewers independently extracted data on study quality, behavioral seizures, and histological, chemical and cognitive outcomes. Data were pooled by means of a meta-analysis. Results Among 17 selected studies; 174 animals from 8 studies with 10 comparison groups showed that exercise intervention after induction of SE significantly decreased spontaneous recurrent seizures with [mean difference (MD) = − 1.80, 95% confidence interval (CI): − 3.22, − 0.37, p = 0.02] and 60 animals showed statistically significant decrease in latency in Morris water maze (standardized mean difference (SMD) = − 2.57, 95% CI: − 4.06, − 1.08, p = 0.0007). Although not statistically significant, still a remarkable increase in number of CA1 neurons and hippocampal BDNF level (MD = 2.27, [95% CI: − 1.20, 5.73], p = 0.19, SMD = 1.07, [95% CI: − 0.36, 2.51], p = 0.14 respectively) and a decrease in mossy fibers sprouting (SMD = − 1.03, [95% CI: − 3.06, 1.00], p = 0.32) were observed. PT interventions in 72 animals before induction of SE showed favorable increase in latency to develop SE (MD = 8.34, [95% CI: − 3.10, 19.78], p = 0.15) but no remarkable improvements in latency for the first motor sign and motor signs intensity. Conclusions PT after SE reduces the recurrent seizures and improves the morphological, biochemical and cognitive profiles of pilocarpine epileptic models. Resistance PT was identified as particularly effective in reducing behavioral seizures. The efficacy of training was also dependent upon duration.