Neuroprotection Strategies to Induce CNS Resilience and Functional Recovery

Disorders of the central nervous system (CNS), including neurodegenerative, ischemic, neuroinflammatory, and traumatic conditions, remain leading causes of disability and cognitive decline worldwide. Despite major advances in understanding disease mechanisms, clinically effective neuroprotective therapies are still scarce. A central obstacle is translating mechanistic insights into actionable targets and therapeutic regimens that robustly activate endogenous protective programs, preserve neural circuit integrity, and sustain CNS homeostasis amid diverse stressors.Neuroprotection is not only a reaction to injury: it can be proactively induced, primed, and strengthened through coordinated molecular, cellular, and physiological adaptations that confer resilience. Such protective states arise from integrated neuronal, glial, and neurovascular responses that stabilize synaptic function and excitatory–inhibitory balance, optimize metabolic efficiency, and maintain redox control. We encourage contributions on neurotransmitter transporters and related solute carrier families as modulators of synaptic transmission and vulnerability during metabolic or inflammatory challenges.At the subcellular level, mitochondrial quality control and bioenergetic flexibility are pivotal for maintaining respiratory capacity, membrane potential stability, organelle turnover, and adaptive metabolic reprogramming. Complementary redox and repair systems, including antioxidant response pathways, NAD+-dependent processes, thiol-based regulation, and hypoxia-adaptive programs, can limit oxidative and nitrosative stress while enabling recovery. Neuroimmune and neurovascular components are equally critical: interventions that shift microglia and astrocytes toward anti-inflammatory or pro-resolving phenotypes, preserve synapse-supportive functions, reinforce blood–brain barrier integrity, and maintain neurovascular coupling are in scope.This Research Topic will synthesize mechanistic and translational advances that clarify how neuroprotective states are established, maintained, and disrupted, and how they can be therapeutically enhanced to promote CNS resilience and functional recovery. We particularly welcome studies on inductive paradigms such as ischemic/remote/pharmacological preconditioning, hormesis, hypoxic training, synaptic homeostasis, and metabolic adaptation. We also invite work on pathopharmacological determinants of CNS vulnerability, including polypharmacy effects, drug–disease interactions, anticholinergic or sedative burden, glucocorticoid influences, and vascular dysregulation. Studies employing advanced models (e.g., human iPSC-derived cultures, organoids, microfluidic platforms, genetically modified organisms) and innovative methodologies (e.g., chemogenetics, optogenetics, single-cell and spatial omics, proteomics, high-resolution imaging) are encouraged.We welcome Original Research, Reviews, Mini-Reviews, Perspectives, and Opinion articles. We particularly encourage submissions on:1. Inductive paradigms of neuroprotection and cross-tolerance.2. Pharmacological and physiological strategies to prime protective states.3. Pathopharmacological factors that modulate CNS vulnerability.4. Intrinsic regulatory pathways (neurotrophic, neurotransmitter, transcriptional/epigenetic, hormonal, neuroimmune).5. Modulators of resilience (exercise, sleep, aging, metabolic stress, sex differences, comorbidities).6. Neurovascular interactions (vascular dysfunction, BBB integrity, systemic inflammation, disease-specific processes).7. Therapeutic targets in metabolic, mitochondrial, redox, and glial pathways.8. Biomarkers, endpoints, and study designs that bridge preclinical findings to clinical translation.By integrating pharmacology and neuroscience from target identification through preclinical and clinical validation, this collection aims to define actionable targets, reliable biomarkers, and robust endpoints that accelerate next-generation neuroprotective interventions. Topic editors: Mauro Cunha Xavier Pinto, Leon Maing Tai, Friederike Klempin Source: https://www.frontiersin.org/research-topics/78263/neuroprotection-strategies-to-induce-cns-resilience-and-functional-recovery