TNF and ischemia: Physical exercise has also been shown to provide endogenous neuroprotection as it reduces leukocytes infiltration and accumulation in the brain parenchyma in the setting of ischemia/reperfusion injury [46] and it reduces hippocampal TNF-α cell death signaling pathways in a chemical-induced injury model (i.e., using the prototypical neurotoxicant Trimethyltin, TMT) [20].