Interferon-Gamma and Interleukin-1Beta Enhance the Secretion of Brain-Derived Neurotrophic Factor and Promotes the Survival of Cortical Neurons in Brain Injury

Abstract

Neuro-inflammation is associated with the production of cytokines, which influence neuronal and glial functions. Although the proinflammatory cytokines interferon-γ (IFN-γ) and interleukin-1Beta (IL-1β) are thought to be the major mediators of neuro-inflammation, their role in brain injury remains ill-defined. The objective of this study was to examine the effect of IFN-γ and IL-1β on survival of cortical neurons in stab wound injury in mice. A stab wound injury was made in the cortex of male BALB/c mice. Injured mice (I) were divide into IFN-γ and IL-1β treatment experiments. Mice in I + IFN-γ group were treated with IFN-γ (ip, 10 µg/kg/day) for 1, 3 and 7 days and mice in I + IL-1β group were treated with 5 IP injection of IL-1β (0.5 µg /12 h). Appropriate control mice were maintained for comparison. Immunostaining of frozen brain sections for astrocytes (GFAP), microglia (Iba-1) and Fluoro-Jade B staining for degenerating neurons were used. Western blotting and ELISA for brain-derived neurotrophic factor (BDNF) were done on the tissues isolated from the injured sites. Results showed a significant increase in the number of both astrocytes and microglia in I + IFN-γ and I + IL-1β groups. There were no significant changes in the number of astrocytes or microglia in noninjury groups (NI) treated with IFN-γ or IL-1β. The number of degenerating neurons significantly decreased in I + IFN-γ and I + IL-1β groups. GFAP and BDNF levels were significantly increased in I + IFN-γ and I + IL-1β groups. Interferon-γ and IL-1β induce astrogliosis, microgliosis, enhance the secretion of BDNF, one of the many neurotrophic factors after brain injury, and promote the survival of cortical neurons in stab wound brain injury.