Neurofunctional and Clinical Effects of Intranasal Human Recombinant Nerve Growth Factor in Children with Acquired Brain Injury

Background: Traumatic brain injury (TBI) and hypoxic-ischemic encephalopathy (HIE) cause significant pediatric morbidity through primary insults and secondary cascades like excitotoxicity, neuroinflammation, and impaired plasticity. Nerve growth factor (NGF) promotes neuroprotection, anti-inflammation, and repair, but delivery challenges persist. This review evaluates preclinical and clinical evidence on intranasal human recombinant NGF (hr-NGF) to enhance neurorepair in pediatric TBI and HIE patients. It aims to clarify the potential of intranasal hr-NGF as part of future multimodal approaches to enhance brain repair and improve functional recovery across the lifespan. Methods: A PRISMA-guided literature search (2000–2025) was conducted across Scopus, PubMed, and Cochrane CENTRAL using terms like “intranasal NGF”, “TBI”, “HIE”, and “pediatric”. Eligible studies involved pediatric brain injury patients receiving NGF, with outcomes via clinical scales, imaging, or EEG. Results: Preclinical models showed that intranasal NGF reduces lesion volume, inflammation, and deficits while boosting angiogenesis and cholinergic function. Clinically, one child with meningitis and five TBI cases exhibited improved consciousness, spasticity, motor scores, cognition, and brain imaging. Three HIE cases gained voluntary movements, expressivity, and perfusion. No adverse events occurred related to hr-NGF administration. Conclusions: Intranasal hr-NGF safely reactivates plasticity in pediatric brain injury, yielding motor, cognitive, and neurophysiological gains. Preliminary data support multimodal use, but randomized trials are needed to optimize protocols and confirm efficacy.