Role of innate inflammation in traumatic brain injury

Abstract

Traumatic brain injury is one of the leading causes of morbidity and mortality throughout the world. Its increasing incidence, in addition to its fundamental role in the development of neurodegenerative disease, proves especially concerning. Despite extensive preclinical and clinical studies, researchers have yet to identify a safe and effective neuroprotective strategy. Following brain trauma, secondary injury from molecular, metabolic, and cellular changes causes progressive cerebral tissue damage. Chronic neuroinflammation following traumatic brain injuries is a key player in the development of secondary injury. Targeting this phenomenon for development of effective neuroprotective therapies holds promise. This strategy warrants a concrete understanding of complex neuroinflammatory mechanisms. In this review, we discuss pathophysiological mechanisms such as the innate immune response, glial activation, blood-brain barrier disruption, activation of immune mediators, as well as biological markers of traumatic brain injury. We then review existing and emerging pharmacological therapies that target neuroinflammation to improve functional outcome.

Cortical and Subcortical Alterations and Clinical Correlates after Traumatic Brain Injury

“…In accordance with previous reports, TBI patients presented common abnormalities of brain morphology despite heterogeneity in injury severity and mechanisms, extent of focal insults, and time since injury [ 23 , 24 , 25 ]. Despite widespread atrophy across the cortical and subcortical regions, only a relatively small subset of this pattern of damage–mainly in the left inferior temporal gyrus and medial temporal lobe, supplementary motor area, thalamus, and ACC–were highly implicated in the post-traumatic cognitive impairment and psychiatric complaints.…”

Systemic inflammation as a biomarker of seizure propensity and a target for treatment to reduce seizure propensity

“…However, inflammatory cascades are complex incorporating interconnected sets of networks. 50,198 Consequently, interfering in the function of just one component can sometimes appreciably reduce the extent and severity of inflammation. 199 More than a decade ago, antibodies that neutralize a single cytokine were known to have broad anti-inflammatory effects.…”

“…Some might appear to target specific steps in the inflammatory process. However, inflammatory cascades are complex incorporating interconnected sets of networks 50,198 . Consequently, interfering in the function of just one component can sometimes appreciably reduce the extent and severity of inflammation 199 …”

Sex, Genes, and Traumatic Brain Injury (TBI): A Call for a Gender Inclusive Approach to the Study of TBI in the Lab

“…Like the primary injury, if untreated, this secondary phase can lead to a manifestation of clinical or behavioral symptoms, including death (Lenzlinger et al, 2001 ; Bramlett and Dietrich, 2007 ; Maas et al, 2008 ). The majority of research focuses on both decreasing the chance of injury and decreasing the secondary effects of that injury (Fitch et al, 1999 ; Day et al, 2013 ; Kim et al, 2015 ; Ripley et al, 2020 ; Bourgeois-Tardif et al, 2021 ). Severe symptoms include long-term cognitive or behavioral deficits, while moderate to mild symptoms include headaches, dizziness, nausea, and short-term amnesia (Prins et al, 2013 ).…”