Early serum and microglial expression of tumor necrosis factor‐α after experimental traumatic brain injury contributes to behavioral deficits

Abstract

Traumatic brain injury (TBI) induces a glial response in which both microglia and astrocytes become activated and produce tumor necrosis factor-alpha (TNF-α). The interrelationship between neurons, microglia, and astrocytes and TNF- α remains poorly understood. Here, we examined the activation of neurons or microglia or astrocyte -TNF-α double positive cells and their involvement in the outcome after TBI. We show that the markers of the microglia-TNF-α double- positive cells, but not the astrocytes or the neurons-TNF- α double positive cells in the contusion brain area at 3 days after TBI. In addition, TBI causes both cerebral contusion and motor dysfunction. There is also a trend toward enhancement of TNF-α production in serum toward the end of the trial (14 days after TBI). Etanercept (a TNF- α antagonist) administrated i.p. once (5mg/ kg of body weight) per 12 hours for consecutive 3 days starting after TBI, significantly reduces TBI- induced increased numbers of the microglia-TNF- α double- positive cells in the ischemic brain areas, brain infarction, and motor dysfunction evaluated at 3 days after TBI. The increased serum levels of TNF- a at the end of the TBI trial are also attenuated by etanercept therapy. Our findings indentify a role for production of TNF- α by microglia in affecting the outcomes of TBI in rats. Etanercept selectively inhibits the activation of microglial cells- TNF- α double positive cells in ischemic brain areas after TBI, which might be one of the mechanisms underlying the therapeutic benefits of etanercept treatment of TBI.