Tumor necrosis factor reduces the amplitude of rat cortical spreading depression in vivo.

摘要: Objective Brain damage and ischemia often trigger cortical spreading depression (CSD), which aggravates brain damage. The proinflammatory cytokine tumor necrosis factor (TNF) is significantly upregulated during damage, but it unknown whether TNF influences in cerebral cortex vivo. This question important because not only furthers inflammatory reactions might also be neuroprotective. Here we tested the hypothesis that affects CSD, explored direction CSD modified by TNF. Methods CSD, elicited pressure microinjection of KCl, was recorded anesthetized rats mice. administered locally into a trough, providing local treatment area. For further analysis, antibodies to receptor (TNFR) 1 or 2 were applied, monitored TNFR1 TNFR2 knockout γ-Aminobutyric acid (GABA)A receptors blocked bicuculline. Immunohistochemistry localized expression TNFR2. Results Local application reduced dose-dependently amplitude CSD. effect prevented blockade TNFR1. at neurons including parvalbumin-positive inhibitory interneurons, GABAA bicuculline reduction amplitudes TNF. Interpretation We identified functional link between activates interneurons. resulting release GABA reduces amplitudes. In this manner, neuroprotective pathological conditions. Ann Neurol 2014;76:43–53