Intraventricular continuous BDNF administration ameliorates neuroinflammation and enhances neurogenesis against rodent intracerebral hemorrhage model

Ting-Chun Lin¹Masahito Kawabori^1*Erika Yoshie¹Yo Nakahara¹Li-Kai Tsai²Miki Fujimura¹

• ¹Hokkaido University, Sapporo, Japan
• ²National Taiwan University, Taipei, Taiwan

Objective: Brain-derived neurotrophic factor (BDNF) is a pivotal growth factor for neuronal survival; however, its precise role following intracerebral hemorrhage (ICH) remains poorly understood. This study sought to investigate whether intraventricular administration of BDNF could enhance neurogenesis and ameliorate neuroinflammation, resulting in improvement of neurological outcomes in a rat ICH model.Methods: Male Sprague-Dawley rats were utilized to create an acute ICH model by collagenase infusion into the internal capsule. An intraventricular minipump was subcutaneously implanted, with the catheter tip inserted into the contralateral ventricle to deliver BDNF for 7 consecutive days. The rats were assigned to one of three experimental groups; the BDNF group, the anti-BDNF antibody group, and the sham group. Functional assessment was conducted up to 14 days post-ICH, and immunohistochemical analysis was performed to evaluate neurogenesis, apoptosis, and neuroinflammation in the perihematomal area and the subventricular zone (SVZ).Results: BDNF treatment significantly increased the proliferation of neural stem cells in the perihematomal region. It also reduced the neuroinflammation 14 days post-ICH. Additionally, BDNF treatment demonstrated a favorable neurological function at 14 days post-ICH.Conclusions: Intraventricular administration of BDNF demonstrated favorable recovery after ICH by reducing inflammation and enhancing neurogenesis.