Novel insights into neuroinflammatory mechanisms in traumatic brain injury: Focus on pattern recognition receptors as therapeutic targets

Traumatic brain injury (TBI) is a major global health concern and a leading cause of morbidity and mortality. Neuroinflammation is a pivotal driver of both the acute and chronic phases of TBI, with pattern recognition receptors (PRRs) playing a central role in detecting damage-associated molecular patterns (DAMPs) and initiating immune responses. Key PRR subclasses, including Toll-like receptors (TLRs), NOD-like receptors (NLRs), and cGAS-like receptors (cGLRs), are abundantly expressed in central nervous system (CNS) cells and infiltrating immune cells, where they mediate immune activation, amplify neuroinflammatory cascades, and exacerbate secondary injury mechanisms. This review provides a comprehensive analysis of these PRR subclasses, detailing their distinct structural characteristics, expression patterns, and roles in post-TBI immune responses. We critically examine the molecular mechanisms underlying PRR-mediated signaling and explore their contributions to neuroinflammatory pathways and secondary injury processes. Additionally, preclinical and clinical evidence supporting the therapeutic potential of targeting PRRs to mitigate neuroinflammation and improve neurological outcomes is discussed. By integrating recent advancements, this review offers an in-depth understanding of the role of PRRs in TBI pathobiology and underscores the potential of PRR-targeted therapies in mitigating TBI-associated neurological deficits.