Voluntary running wheel activity reduces seizure burden and affords neuroprotection in a mouse model of acquired epilepsy

Abstract

Objective: Physical exercise may improve neurological deficits and neuronal damage after acute brain injuries and decrease established seizures. We investigated whether voluntary running wheel (RW) activity affects epileptogenesis in a mouse model of acquired epilepsy compared to sedentary mice. Methods: Epilepsy was induced by intra-amygdala kainate causing status epilepticus (SE) in adult male mice. Sham mice were implanted with electrodes and injected with saline, and matched to experimental mice. In the RW-1 protocol, SE mice were trained to run for 5 weeks before SE induction and for 6 weeks thereafter. In the RW-2 protocol, mice began using RWs 24 h post-SE for 10 weeks. At the end of each protocol, electrocorticography (ECoG) was recorded for 2 weeks (24/7) in the absence of RWs. Matched sedentary mice were kept in home cages without RWs, subjected to SE, and had ECoG monitored. At the end of experiment, all mice were processed for assessing hippocampal neuronal cell loss (Nissl staining), hilar mossy cells (GluR2/3 staining), and blood–brain barrier (BBB) damage (serum matrix metalloproteinase-9 [MMP-9] by enzyme-linked immunosorbent assay). Neuroinflammation (reverse-transcriptase quantitative polymerase chain reaction) and albumin level (western blot) were also measured in the hippocampus of RW-1 mice 72 h post-SE, together with serum MMP-9. Results: RW activity in SE mice reduced the incidence of epilepsy (RW-1 by 38%; RW-2 by 54%, p