Role of Pattern Recognition Receptors (PRRs) in Spinal Cord Injury (SCI): A Comprehensive Review

Spinal cord injury (SCI) is a severe disorder of the central nervous system (CNS) that leads to impairments in both motor and sensory functions. Immune system plays a critical role in SCI through various mechanisms conducted by neurons, glial cells, and their related secretions. Immune cells receive signals via their membrane and cytoplasmic receptors; among the most well-known of these are pattern recognition receptors (PRRs). This review examines structure, different subtypes, and the role of PRRs in SCI by summarizing animal studies. To identify relevant studies, a comprehensive literature search was carried out from inception to March 2026 using PubMed and Google Scholar databases. The search strategy combined Medical Subject Headings (MeSH) terms and keyword variations related to spinal cord injury, pattern recognition receptors, neuroinflammation, glial cells, immunomodulation and therapeutic interventions. Key findings include major families of PRRs, which contain Toll-like receptors (TLRs), NOD-like receptors (NLRs), C-type lectin receptors (CLRs), RIG-I-like receptors (RLRs), AIM2-like receptors (ALRs), and cyclic GMP-AMP synthase (cGAS), which are located on the cell surface, in endosomal compartments, or in the cytoplasm. Activation of PRRs can trigger signaling cascades that are involved in neuroinflammation, microglial polarity, gliosis, pyroptosis, excitotoxicity, demyelination, and locomotor function. Additionally, preclinical studies in SCI animal models represent PRRs as potential therapeutic targets, in which activators of TLR2 or suppressors of other types of PRRs could represent a promising avenue for SCI recovery. Further investigations are warranted to clarify the underlying mechanisms of PRRs and their immunomodulatory effects on SCI.