Role of Inflammation in Secondary Injury Progression after Traumatic Brain Injury and Spinal Cord Injury

Abstract

Trauma to the brain or spinal cord is a type of injury that triggers a cascade of secondary pathophysiological events after the primary mechanical trauma. Neuroinflammation is indeed of foremost importance, acting both as a mediator for tissue repair and an instigator for progressive neurodegeneration. Activated microglia and astrocytes, peripherally derived immune cells infiltrating that site, mediate a complex interaction involving cytokines, oxidative stress, mitochondrial dysfunction, and neurovascular disruption. This early inflammatory signaling helps remove debris and support neuronal regeneration in traumatic brain injury (TBI) and spinal cord injury (SCI). However, when this particular inflammation becomes chronic, it leads to glial damage with aberrant synaptic connections and irreversible harm to neural network circuitry. Mediators, including IL-1β, TNF-α, and the NLRP3 inflammasome, have been identified as promising therapeutic targets; cutting-edge therapies, ranging from small-molecule inhibitors to mitochondrial stabilizers to cell-based interventions, have shown efficacy in preclinical models. Nonetheless, the translation to the clinic has been hindered through shortcomings in classical animal models, failure to integrate biomarker application, and an inability to account for the heterogeneity of human central nervous system (CNS) injury. To bridge this gap, temporally targeted immunomodulation, precision diagnostics, and systems-level approaches will need to align with the molecular pathology involved in disease intervention. Understanding this dual property within post-traumatic inflammation presents an important frontier to develop truly efficacious neuroprotective therapies