Mechanisms of Glia and Non-coding RNAs in Traumatic Brain Injury: Insights and Intervention Strategies

Traumatic brain injury (TBI) is a globally prevalent neurological disorder, with longterm deteriorating neurological deficits (especially learning and memory impairments). Classified into primary and secondary injuries, TBI's secondary phase is characterized by inflammation and apoptosis-key pathological processes driving further neurological dysfunction with complex bidirectional regulation. This study systematically elaborates the core mechanisms: glial cells act as central "regulatory hubs" that modulate their phenotype via proinflammatory factor release and key signaling pathway activation, directly or indirectly inducing neuronal apoptosis; non-coding RNAs [Long Non-coding RNAs (lncRNAs), MicroRNAs (miRNAs)] function as "molecular bridges" by targeting glial activation, inflammatory factor secretion, and apoptosis-related pathways [e.g., LINC00707/miR-30a-5p, miR-21-5p/ phosphatase and tensin homologue (PTEN)]. Additionally, diverse therapeutic strategies are summarized: pharmacological agents (e.g., minocycline, dexmedetomidine) inhibit inflammatory pathways and reduce apoptosis-related proteins; mesenchymal stem cell therapy exerts immunomodulatory and neuroregenerative effects; nanoparticles enable precise drug delivery; hyperbaric oxygen therapy blocks the vicious cycle by improving oxygenation; gut microbiota interventions restore homeostasis via metabolic and immune modulation. In conclusion, in-depth analysis of glial cells and non-coding RNAs in TBI-induced inflammation and apoptosis provides a theoretical basis for developing targeted therapies, holding great significance for improving TBI patient prognosis.