Neurotrophic Factors in Stroke, Traumatic Brain Injury, and Neurodegeneration: A Convergent Pathophysiological and Translational Perspective.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing preclinical mechanisms and clinical trial landscapes without systematic review methodology.
PubMed 42530052 · doi:10.31083/JIN51543
What was done
This narrative review evaluated the shared pathophysiological mechanisms connecting stroke, traumatic brain injury, Alzheimer's disease, and Parkinson's disease. It examined the biology and receptor pathways of major neurotrophic factors (including NGF, BDNF, NT-3, GDNF, CNTF, and VEGF), synthesized preclinical findings across protein, gene, and cell-based approaches, and evaluated clinical delivery platforms such as viral vectors, lipid nanoparticles, exosomes, small-molecule mimetics, and intranasal administration.
What was found
No quantitative findings or effect sizes were reported in the abstract. Preclinical models demonstrated beneficial effects on neuroprotection, neurogenesis, and synaptogenesis. Early-phase clinical trials testing adeno-associated virus-mediated GDNF and neurturin in Parkinson's disease, as well as NGF and BDNF gene therapies in Alzheimer's disease, showed acceptable safety but modest or inconsistent efficacy due to blood-brain barrier delivery constraints, invasive neurosurgical requirements, restricted target coverage, and patient heterogeneity.
Why it matters
The review identifies delivery barriers and limited target coverage—rather than biological invalidity—as the primary bottlenecks preventing neurotrophic therapies from achieving clinical efficacy in acute and chronic neurological disorders.
Limits
This is a narrative review with no systematic search criteria or quantitative meta-analysis. The abstract provides no specific numerical data, sample sizes, or effect estimates. Evidence reflects heterogeneous early-phase human trials and animal models.
Cited by
- supports Brain-derived neurotrophic factor (BDNF) plays an active role in enhancing neuroplasticity and stimulating the generation of new neurons.