Aim To evaluate the therapeutic potential of nutritional supplementation as a complementary strategy to mitigate secondary injury mechanisms and promote recovery in spinal cord injury (SCI). Methods This narrative review synthesizes current preclinical and clinical evidence on the role of micronutrients and macronutrients in SCI management, focusing on their mechanisms of action in neuroprotection, neuroregeneration, and functional recovery. Results SCI is a severe neurological condition characterized by long-term motor, sensory, and autonomic dysfunction, largely driven by secondary injury processes such as oxidative stress, neuroinflammation, excitotoxicity, and apoptosis. Evidence indicates that micronutrients—including vitamins A, B complex, C, D, and E, as well as trace elements such as selenium, zinc, copper, and magnesium—exert neuroprotective effects by modulating inflammatory responses, reducing oxidative damage, supporting mitochondrial function, and enhancing myelination. Additionally, macronutrients such as carbohydrates, amino acids, omega-3 fatty acids, and bioactive compounds including alpha-lipoic acid, N-acetylcysteine, and acetyl-L-carnitine contribute to axonal regeneration, metabolic support, and functional recovery. Collectively, these nutrients target key pathophysiological pathways involved in secondary SCI progression Conclusions Nutritional supplementation represents a promising, safe, and accessible adjunctive strategy to enhance neuroprotection and improve outcomes in individuals with SCI. However, further research is required to optimize dosing, timing, and combinatorial approaches to maximize therapeutic efficacy.
Mild traumatic brain injury (mTBI) often creates a sequela of symptoms that complicate safely participating in aerobic exercise. Although exertional assessments have been used to evaluate exercise tolerance, data on the feasibility of using test-derived metrics to guide the intensity of aerobic exercise interventions in community-dwelling adults is yet to be presented. This secondary analysis of a wider pilot randomized control trial examined whether a modified exertional bike test (MEBT) could be used to effectively individualize supervised virtual aerobic exercise without exacerbating symptoms in individuals with a mTBI. Adults (18-55 years) diagnosed of mTBI within the previous 12 months completed the MEBT and were randomized to either a 12-week supervised virtual aerobic exercise intervention or active balance control. Those randomized to the aerobic group exercised at 65-80% of HR at MEBT-derived symptom threshold or volitional exhaustion. Descriptive session outcomes, Spearman correlations, and Fisher's z tests assessed (1) the feasibility of symptom-threshold HR intervention metrics, (2) changes in the HR-symptom relationship over time, and (3) the influence of mTBI-related confounders on HR-symptom associations. Participants completed 95.6% of aerobic sessions, with symptom exacerbation (>= 3-unit increase) reported in just 3.8% of sessions. Ten of 12 participants displayed a decreased, or negative, HR-symptom severity association over time. In addition, Fisher's z tests revealed confounding variables did not meaningfully modify the HR-symptom association. Sub-symptom-thresholded exercise sessions limited symptom exacerbation, uncoupled the HR-symptom relationship, and improved exercise tolerance over time. These findings highlight the feasibility of exertional symptom-guided virtual aerobic exercise following mTBI and support progression towards larger efficacy trials.
It has been well established that physical exercise is associated with augmented cognitive function, but the exact mechanisms by which peripheral activity affects the plasticity of the brain remain mechanistically elusive. This narrative review synthesises evidence from mouse models and human studies to clarify how physical exercise may enhance hippocampus-dependent cognition through systemic, neurovascular, immune, and metabolic mechanisms instead of direct “brain training” alone. This distinction is supported by the limited far transfer shown in many cognitive training models, wherein improvements tend to remain task- or circuit-specific rather than reflecting general skill transfer. In rodent models, voluntary physical exercise improves learning, memory, and pattern separation, and these effects correlate with changes in hippocampal neurogenesis, synaptic plasticity, vascular remodelling, and neuroimmune state. A smaller pool of plasma-transfer studies suggests that these effects carry over between individual mice via circulating exercise-induced factors, reproducing select molecular and behavioural effects in completely sedentary recipient mice, but in humans, the causal relevance of such pathways remains unresolved. In rodent transfer experiments, exercise-conditioned blood plasma has been reported to reduce neuroinflammation and to modulate brain endothelial cells, positioning the neurovascular unit as a critical interface for peripheral-to-central nervous system communication. Beyond clusterin and Gpld1, a conceptual muscle-brain endocrine axis is emerging, where specific myokines (e.g., irisin, cathepsin B) and downstream metabolites released during physical exercise may act on vascular and immune interfaces to modulate structural plasticity. Emerging human data reinforce some of these investigated mechanisms, although causal relationships have yet to be established and remain limited. Overall, the available evidence supports a model whereby physical exercise improves cognitive function through changes in the immunometabolic environment, supporting hippocampal plasticity. These pathways may inform future studies aiming to preserve cognitive health during ageing, and the development of exercise-mimetic therapeutic strategies.
Feedback is an essential component of motor learning and rehabilitation. Although extrinsic feedback is widely used in stroke rehabilitation, excessive dependence on external cues may limit opportunities for independent movement regulation. Training that emphasizes intrinsic feedback during visual deprivation (VD) may provide individuals with greater opportunities to perceive and regulate their movements using internally available sensory information. This study investigated the effects of gait training with intrinsic feedback on balance and gait abilities in individuals with stroke compared with extrinsic feedback training and conventional physical therapy. Thirty-six individuals with stroke were randomly assigned to the gait training with intrinsic feedback (GIF) group, gait training with extrinsic feedback (GEF) group, or control group (CG). The GIF performed forward and backward linear and curvilinear gait tasks on stable and unstable surfaces during VD without continuous verbal guidance. The GEF performed the same gait tasks during VD while receiving continuous verbal guidance, whereas the CG received conventional physical therapy. All interventions were conducted for 30 min, five times per week, for 8 weeks. Outcome measures included the Four Square Step Test (FSST), weight distribution, spatiotemporal gait variables, center of pressure (COP) variables, and the 10-Meter Walk Test (10 MWT). Significant group & times; time interactions were observed for the FSST, weight distribution, gait velocity, cadence, paretic stance phase, paretic swing phase, paretic step time, stride time, and the 10 MWT (p < 0.05). The GIF demonstrated significantly greater improvements than both the GEF and CG in the FSST, gait velocity, cadence, paretic step time, stride time, and the 10 MWT (p < 0.05). The GIF also showed greater improvement than the CG in weight distribution (p < 0.05). These findings suggest that gait training emphasizing intrinsic feedback during VD may provide additional benefits for selected aspects of balance and gait performance in individuals with stroke.
Background Resveratrol has been shown to play a neuroprotective role in diabetic cognitive dysfunction. We determined whether resveratrol improved diabetic cognitive dysfunction through ferroptosis regulation, and explored the potential mechanism.Methods Rats were fed with a high-sucrose and high-fat diet combined with streptozotocin for establishing a diabetic model, followed by resveratrol treatment with or without erastin (a classical ferroptosis activator). Cognitive abilities were evaluated with novel object recognition test and Morris water maze test. Neuronal damage was determined using Nissl staining and Fluoro-Jade B staining. Ferroptosis-related factors such as glutathione (GSH), 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS) and iron (Fe2+) levels were evaluated. Mitochondrial function was assessed by mitochondrial morphology, mitochondrial swelling, mitochondrial membrane potential (MMP), and ATP content. Western blot was performed to measure Sirtuin 1 (Sirt1) and Sonic hedgehog (Shh) signaling pathway, and ferroptosis-related proteins. Besides, the cellular localization of Sirt1 and Shh was assessed using immunofluorescence.Results Resveratrol ameliorated cognitive dysfunction and neuronal damage in diabetic rats and blocked hippocampal neuron ferroptosis, which were abolished by erastin. Resveratrol ameliorated hippocampal mitochondrial dysfunction (decrease of mitochondrial swelling and increases of MMP and ATP) in diabetic rats. Resveratrol treatment upregulated Sirt1 and Shh expressions in NeuN-positive neurons in the hippocampus of diabetic rats. Moreover, Shh knockdown reversed the protective effects of resveratrol on ferroptosis, cognitive dysfunction, and neuron loss.Conclusion Resveratrol conferred neuroprotective effect on diabetic cognitive dysfunction by maintaining mitochondrial function and inhibiting hippocampal neuron ferroptosis via Sirt1/Shh signaling.
