Elevated release of inflammatory mediators such as IL-1β, IL-2, IL-6, and TGF-α as well as increased expression of COX-2/E2 (PGE2), high mobility group box 1 (HMBG1) toll-like receptors 4 (TLR4) released from neurons, astrocytes, and microglia, following epileptogenic insult (SE, TBI) cause development of seizures and possibly depression [28, 29]. This evidence concerns the gene TLR4 and major depressive disorder.