NEUROPLASTICITY AFTER BRAIN INJURY: CELLULAR MECHANISMS AND THERAPEUTIC OPPORTUNITIES

Abstract

Neuroplasticity is the capacity of the central nervous system to modify synaptic strength, neuronal structure, and functional networks in response to experience or injury. Following acquired brain injury, including ischemic stroke, traumatic brain injury, intracerebral hemorrhage, subarachnoid hemorrhage, and hypoxic-ischemic injury, neuroplastic mechanisms support partial recovery of neurological functions through synaptic remodeling, dendritic spine turnover, axonal sprouting, cortical reorganization, and glial responses. These processes are regulated by molecular pathways involving BDNF/TrkB signaling, neurotransmitter-dependent changes in excitability, inflammatory responses, and extracellular inhibitors of axonal growth. Rehabilitation exploits these mechanisms through repetitive, task-specific training, while neuromodulation, robotics, virtual reality, brain-computer interfaces, and biological therapies provide additional approaches. Artificial intelligence may further improve recovery prediction and personalization of rehabilitation. However, substantial variability between patients, limitations of experimental models, maladaptive plasticity, and difficulties in measuring cellular processes in humans remain major challenges. This review summarizes the principal cellular mechanisms of post-injury neuroplasticity and evaluates current and emerging therapeutic strategies for promoting functional neurological recovery.