BDNF plasmid hydrogel promotes neuroprotection and neurogenesis in rats with intracerebral hemorrhage

Intracranial hemorrhage (ICH) remains a challenging disease worldwide with high mortality, morbidity, and disability. The combination of brain-derived neurotrophic factor (BDNF) therapy and hydrogel implantation is a potential novel treatment for promoting neuroprotection, neurogenesis, and neurological recovery. Hydrogel may serve as a vector for gene delivery. This study examined the therapeutic efficacy of BDNF plasmid delivered with a chitosan-based self-healing hydrogel in treating ICH rats. Direct injection of BDNF plasmid-containing hydrogel into bled brain tissue caused an approximately 1.8-fold increase in BDNF expression and behavioral improvements of at least 80%. Furthermore, medical imaging revealed that untreated rats experienced approximately 6% brain atrophy, while BDNF plasmid-treated rats showed reduced atrophy of 2%. Postmortem histological examination revealed that compared to untreated rats, rats treated with BDNF had a five fold increase in the number of neuroblasts, whereas the number of macrophages decreased by half. Conclusively, injection of self-healing hydrogel with BDNF plasmid may be a novel gene therapy approach for post-ICH treatment.