Blocking TNF-α Expression Prevents Blast-Induced Excitatory/Inhibitory Synaptic Imbalance and PV+ Interneuron Loss in the Hippocampus

Traumatic brain injury (TBI) is a major cause of neurological disorder and death in civilian and military populations (citation?). It comprises two components—direct injury from the traumatic impact and secondary injury from ensuing neural inflammatory responses. Blocking tumor necrosis factor-alpha (TNF-α), a central regulator of neural inflammation, has been shown to improve functional recovery after TBI. However, the mechanisms underlying those therapeutic effects are still poorly understood. Here we examined effects of 3,6'-dithiothalidomide (dTT), a potentially therapeutic TNF-α inhibitor, in mice with blast-induced TBI. We found that blast exposure resulted in elevated expression of TNF-α, activation of microglial cells, enhanced excitatory synaptic transmission, reduced inhibitory synaptic transmission, and a loss of parvalbumin-positive (PV+) inhibitory interneurons. Administration of dTT for five days after the blast exposure completely suppressed blast-induced increases in TNF-α transcription, l...