Spinal Cord Injury and Ageing: The Role of Chronic Neuroinflammation.

Abstract

As the global population ages, there is an increasing prevalence of spinal cord injury (SCI) among elderly individuals, accompanied by significant challenges in treatment and recovery. Age-related conditions, such as osteoporosis, muscle atrophy, and impaired balance, predispose older adults to falls and traumatic injuries, leading to worse neurological outcomes compared to younger patients. SCI pathophysiology consists of two phases: the initial mechanical injury and the secondary injury that involves a cascade of pathological events, including ischemia, apoptosis, and neuronal cell death. Chronic neuroinflammation has emerged as a central factor in driving long-term damage after SCI, particularly in older people, where immune senescence and a decreased ability to resolve inflammation contribute to persistent, unresolved inflammation. This prolonged inflammatory state further impedes neural regeneration and functional recovery. Aged animal models have revealed that chronic neuroinflammation is exacerbated by sustained activation of microglia and astrocytes, the infiltration of peripheral immune cells, and the secretion of pro-inflammatory cytokines, creating a pro-inflammatory microenvironment that hinders repair. Furthermore, ageing-related factors such as immunosenescence, autophagy dysfunction, and mitochondrial abnormalities exacerbate inflammation, establishing a vicious injury cycle. Despite promising studies targeting inflammation in young SCI models, there is a critical need for age-specific therapeutic approaches for elderly SCI patients. This review explores the mechanisms of chronic inflammation in aged SCI, examines key cellular mediators, and discusses potential therapeutic strategies, including pharmacological treatments, gene therapy, exosome-based interventions, and rehabilitation. Focusing on age-related differences in inflammation and healing, this work aims to provide a foundation for precision medicine tailored to the ageing population with SCI, ultimately improving clinical outcomes and quality of life for elderly patients.