Synaptic Plasticity and Circuit Rewiring After CNS Injury: Mechanisms of Reorganization and Functional Recovery

Abstract

Central nervous system (CNS) injuries, long regarded as irreversible, are now understood to trigger extensive synaptic plasticity and circuit reorganization that underlie functional recovery. This review synthesizes evidence from molecular, imaging, and transcriptomic studies to elucidate the mechanisms of adaptive and maladaptive neuroplasticity. Activity-dependent NMDA-CaMKII-CREB signaling and neurotrophic support drive synaptic remodeling, while growth-associated proteins (GAP-43) and glial modulation facilitate axonal sprouting. Advances in optogenetics, single-cell transcriptomics, and in vivo imaging reveal dynamic rewiring across scales, reshaping our understanding of CNS repair. Emerging therapeutic strategies; ranging from neuromodulation to gene-based and cell-based interventions, highlight translational opportunities for precision neurorehabilitation. This synthesis uniquely integrates recent molecular, glial, and network-level insights with cutting-edge neurotechnological methods to propose a unified translational framework for adaptive CNS repair.

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