Objective: To verify whether mfat-1 transgenic mice participate in the repair of hypoxic-ischemic brain damage by promoting the proliferation of adult neural stem cells. Methods: In vitro experiments, adult neural stem cells from wild-type and mfat-1 transgenic mice were isolated and cultured, subjected to Oxygen-Glucose Deprivation/Reoxygenation (OGD/R) modeling, and the proliferation of neural stem cells was assessed; in vivo experiments, mfat-1 transgenic mice and their littermates were subjected to Hypoxic-Ischemic Brain Damage (HIBD) modeling, and the proliferation capacity of adult neural stem cells was evaluated. Results: Successful establishment of the mouse HIBD model; successful establishment of the neural stem cell in vitro culture system; adult neural stem cells derived from mfat-1 transgenic mice exhibited higher proliferation ability compared to wild-type mice; mfat-1 transgenic mice showed significantly enhanced proliferation capacity of neural stem cells compared to wild-type mice and displayed better behavioral performance. Conclusion: mfat-1 transgenic mice participate in the repair of hypoxic-ischemic brain damage by promoting the proliferation of mouse neural stem cells. The findings will offer a novel research avenue for ischemic stroke treatment.