Etanercept Attenuates Traumatic Brain Injury in Rats by Reducing Brain TNF-αContents and by Stimulating Newly Formed Neurogenesis

Abstract

It remains unclear whether etanercept penetrates directly into the contused brain and improves the outcomes of TBI by attenuating brain contents of TNF-α and/or stimulating newly formed neurogenesis. Rats that sustained TBI are immediately treated with etanercept. Acute neurological and motor injury is assessed in all rats the day prior to and 7 days after surgery. The numbers of the colocalizations of 5-bromodeoxyuridine and doublecortin specific markers in the contused brain injury that occurred during TBI were counted by immunofluorescence staining. Enzyme immunoassay for quantitative determination of TNF-α or etanercept in brain tissues is also performed. Seven days after systemic administration of etanercept, levels of etanercept can be detected in the contused brain tissues. In addition, neurological and motor deficits, cerebral contusion, and increased brain TNF-α contents caused by TBI can be attenuated by etanercept therapy. Furthermore, the increased numbers of the colocalizations of 5-bromodeoxyuridine and doublecortin specific markers in the contused brain tissues caused by TBI can be potentiated by etanercept therapy. These findings indicate that systemically administered etanercept may penetrate directly into the contused brain tissues and may improve outcomes of TBI by reducing brain contents of TNF-α and by stimulating newly formed neurogenesis.

Therapeutic evaluation of interleukin 1-beta antagonist Anakinra against traumatic brain injury in rats

“…[13] The expression of proinflammatory cytokines at the site of injury, including IL-1β and TNF-α, regulate precise cellular events that occur within the first few hours of TBI and persist in the neural tissue for several days with cytokines also being detectable on microglia, perivascular macrophages, and astrocytes. [14,15] Most important secondary factors leading to further neuronal death are lipid peroxidation, apoptosis, and development of reactive oxygen species. [16][17][18][19][20] In our study, cellular and biochemical changes were observed in order to assess the actual outcome of TBI in relation to short-term histological damage and cytokine expression.…”

Gamma-Secretase Inhibitors Attenuate Neurotrauma and Neurogenic Acute Lung Injury in Rats by Rescuing the Accumulation of Hypertrophic Microglia

“…A moderate percussion injury was produced by rapidly injecting a small volume of saline into the closed cranial cavity. This reproducible and consistent model is associated with a >100-mm 3 cerebral contusion volume and neurological motor deficit within the first 3 days after injury [21]. Sham-operated animals received all the aforementioned surgical procedures, except the injury.…”

Roles of Pro- and Anti-inflammatory Cytokines in Traumatic Brain Injury and Acute Ischemic Stroke

“…Studies by Chio et al have demonstrated that post-TBI i.p. administration of etanercept in the luid percussion model of brain injury in the rat improves motor deicits at 7 days and increases markers of neurogenesis [246], decreases acute TBI-induced rises in glutamate, the lactate/pyruvate ratio, and improves injury-induced motor deicits [247], cognitive deicits in the passive avoidance task [248], and the severity of ischemia at 3 days post-injury [247,248]. A major barrier to the eicacy of etanercept as a TNF-α inhibitor for AIS and TBI is its poor BBB permeability due to its large size.…”