A comprehensive review on adaptive plasticity and recovery mechanisms post‐acquired brain injury

Abstract Adaptive plasticity, the brain's ability to reorganize and form new neural connections after injury, is crucial for recovery following acquired brain injury (ABI). This process involves axonal sprouting, dendritic remodeling, and neurogenesis, which restore neural connections and compensate for lost functions. While neuroinflammation and reactive astrocytes aid tissue repair, optimizing these responses to minimize secondary damage remains a challenge. Brain‐derived neurotrophic factor (BDNF) plays a vital role in neurogenesis and dendritic growth, positioning it as a potential therapeutic target for brain repair. Rehabilitation strategies that stimulate these adaptive changes can enhance neuroplasticity and functional recovery. The complexity of ABI recovery is influenced by factors such as injury severity, age, and genetic and epigenetic factors, which regulate neuronal repair and synaptic plasticity. Maladaptive plasticity refers to compensatory mechanisms that initially aid recovery but ultimately become harmful. Severe injuries like traumatic brain injury (TBI) and stroke can trigger adaptive responses, such as axonal sprouting, but excessive reliance on these processes may become maladaptive. In contrast, mild TBIs offer greater recovery potential. Age‐related differences in plasticity complicate recovery, with younger individuals exhibiting greater plasticity and older adults experiencing reduced plasticity and increased likelihood of maladaptive changes. Genetic factors, such as BDNF gene polymorphisms and DNA methylation, influence recovery outcomes. Neuroinflammation plays a dual role: acute inflammation supports recovery, while chronic inflammation can exacerbate damage. Precision medicine, tailored to an individual's genetic and epigenetic profile, offers promising strategies to optimize recovery. Growth factors like BDNF and insulin‐like growth factor 1 (IGF‐1) are essential for neurogenesis, synaptic plasticity, and neural network reorganization, supporting both structural and functional recovery. However, maladaptive plasticity must be managed carefully for effective recovery. Targeted rehabilitation therapies, along with pharmacological agents and neuromodulation techniques, offer insights into personalized treatment strategies to enhance adaptive plasticity and optimize ABI recovery outcomes. This review explores the mechanisms of adaptive plasticity following ABI and discusses therapeutic interventions to support and optimize recovery, offering promising avenues for improving patient outcomes.