Interleukin-1 Beta Neutralization Attenuates Traumatic Brain Injury-Induced Microglia Activation and Neuronal Changes in the Globus Pallidus

Traumatic brain injury (TBI) increases the risk of delayed neurodegenerative processes, including Parkinson's disease (PD). Interleukin-1beta (IL-1 beta), a key pro-inflammatory cytokine, may promote secondary injury development after TBI. Conversely, neutralizing IL-1 beta was found to improve functional recovery following experimental TBI. However, the mechanisms underlying the behavioral improvements observed by IL-1 beta neutralization are still poorly understood. The present study investigated the role of IL-1 beta on the microglia response and neuronal changes in the globus pallidus in response to diffuse TBI. Mice were subjected to sham injury or the central fluid percussion injury (cFPI) (a model of traumatic axonal injury), and were randomly administered an IL-1 beta neutralizing or a control antibody at 30 min post-injury. The animals were analyzed at 2, 7, or 14 days post-injury. When compared to controls, mice subjected to cFPI TBI had increased microglia activation and dopaminergic innervation in the globus pallidus, and a decreased number of parvalbumin (PV) positive interneurons in the globus pallidus. Neutralization of IL-1 beta attenuated the microglia activation, prevented the loss of PV+ interneurons and normalized dopaminergic fiber density in the globus pallidus of brain-injured animals. These findings argue for an important role for neuro-inflammation in the PD-like pathology observed in TBI.