Neuroinflammation in traumatic brain injury: A chronic response to an acute injury

Abstract

Every year, approximately 1.4 million US citizens visit emergency rooms for traumatic brain injuries. Formerly known as an acute injury, chronic neurodegenerative symptoms such as compromised motor skills, decreased cognitive abilities, and emotional and behavioral changes have caused the scientific community to consider chronic aspects of the disorder. The injury causing impact prompts multiple cell death processes, starting with neuronal necrosis, and progressing to various secondary cell death mechanisms. Secondary cell death mechanisms, including excitotoxicity, oxidative stress, mitochondrial dysfunction, blood–brain barrier disruption, and inflammation accompany chronic traumatic brain injury (TBI) and often contribute to long-term disabilities. One hallmark of both acute and chronic TBI is neuroinflammation. In acute stages, neuroinflammation is beneficial and stimulates an anti-inflammatory response to the damage. Conversely, in chronic TBI, excessive inflammation stimulates the aforementioned secondary cell death. Converting inflammatory cells from pro-inflammatory to anti-inflammatory may expand the therapeutic window for treating TBI, as inflammation plays a role in all stages of the injury. By expanding current research on the role of inflammation in TBI, treatment options and clinical outcomes for afflicted individuals may improve. This paper is a review article. Referred literature in this paper has been listed in the references section. The data sets supporting the conclusions of this article are available online by searching various databases, including PubMed. Some original points in this article come from the laboratory practice in our research center and the authors’ experiences.

Biological links between traumatic brain injury and Parkinson’s disease

“…Brains examined by positron emission tomography (PET) following head trauma for an activated microglial marker, showed an increase in activated microglia up to 17 years after a TBI, which was found to be associated with impaired information processing [123]. Inflammation occurs shortly after initial TBI event (acute sequalae), and can persist for years (chronic sequalae) in the affected areas [134]. Therefore, inflammation can be seen as a "chronic response to an acute event."…”

The CNS lymphatic system modulates the adaptive neuro-immune response in the perilesional cortex in a mouse model of traumatic brain injury

“…Our data suggest that, in the presence of chronic neuro-inflammation (as it is the case after TBI (51, 52)), the neuro- and systemic immune responses are independent. This is apparently in contrast with previously published data (6), where Authors found a substantial correlation between the levels of different T cell populations in the brain and in the blood after TBI.…”

Biologic Effect of Hydrogen Sulfide and Its Role in Traumatic Brain Injury

“…Neuroinflammation, which is characterized by the activation of glial cells, recruitment of neutrophils and macrophages, and upregulation of cytokines, adhesion factors, and chemokines, can be triggered from the surrounding to the site of injury and cause secondary neuronal injury after TBI [ 33 , 34 ]. The pioneering work revealed the anti-inflammatory properties of H 2 S in different disease models.…”