Nerve Growth Factor in Pediatric Brain Injury: From Bench to Bedside

Background: Traumatic brain injury (TBI) and hypoxic-ischemic encephalopathy (HIE) are major causes of long-term neurological disability in children, with limited options for effective neuronal recovery. Recent research has highlighted the therapeutic potential of nerve growth factor (NGF) in promoting neural repair through mechanisms such as neuroprotection, neurogenesis, and the modulation of neuroinflammation. This review evaluates the current evidence on NGF as a treatment strategy for pediatric brain injury, emphasizing its mechanisms of action and translational clinical applications. Methods: A comprehensive review was conducted using the PubMed, Scopus, and Cochrane CENTRAL databases to identify studies published between 1 January 1978 and 1 March 2025, investigating NGF in the context of brain injury. The inclusion criteria comprised studies assessing neurological outcomes through clinical scales, biochemical markers, neuroimaging, or electrophysiological examinations. Results: Seventeen studies met the inclusion criteria, encompassing both preclinical and clinical research. Preclinical models consistently demonstrated that NGF administration reduces neuroinflammation, enhances neurogenesis, and supports neuronal survival following TBI and HIE. Clinical studies, including case reports of pediatric patients treated with intranasal NGF, reported improvements in motor and cognitive function, neuroimaging findings, and electrophysiological parameters, with no significant adverse effects observed. Conclusions: NGF demonstrates significant promise as a neuroprotective and neuroregenerative agent in pediatric brain injury, with both experimental and early clinical evidence supporting its safety and efficacy. Large-scale controlled clinical trials are warranted to validate these preliminary findings and to determine the optimal dosage regimens and administration schedules for NGF in the treatment of TBI and HIE.