Abstract: Objective To investigate the possibility of therapy method in orthotropic transplant fibrin scaffold mixedneural stem cells (NSCs) after traumatic brain injury (TBI), and combined effects of that fibrin scaffold with mild hypothermia (MHT) on TBI in rats. Methods Neural stem cells were separated from E14 Sprague-Dawley rats, and were co-cultured with fibrin scaffold. Scanning electron microscope was used for observing neural stem cell surface morphology in fibrin scaf⁃ fold, and immunofluorescent staining was introduced for detecting cell types. Forty-eight male Sprague-Dawley rats were randomly divided into four groups: TBI group (A), TBI+NSC group (B), TBI+MHT group (C) and TBI+NSC+MHT group (D). TBI model was built with fluid percussion device in group A. Group B was treated with fibrin scaffold carrying neural stem cells after TBI. Group C was treated with MHT for 6 hours after TBI. Fibrin scaffold mixed BrdU labeled neural stem cells were co-transplanted into cortex damage area of group D and mild hypothermia was given for 6 hours. mNSS (modified neuro⁃ logical severity score) and Morris water maze were examined to evaluate the neurologic function at 14 and 28 days after TBI. The rats were sacrificed at 28 days for brain slices. Immunofluorescent staining was used to examine the migration and differ⁃ ention of NSCs in vivo. Results No obvious morphology changes were observed in NSCs, which were co-cultured in fibrin scaffold. The specific marker Nestin was expressed in detected NSCs by immunofluorescence, which indicated that NSCs were still alive in the co-coture fibrin scaffold. The mNSS scores were significantly lower in group D than those of groupA, B and C at day-14 and day-28 (P < 0.05). Results of Morris water maze showed that the escape latency was significantly short⁃ er in group D than that of group A, B and C (P < 0.05). BrdU labled NSCs was found differentiated into neurons in group D at day 28. Conclusion Fibrin scaffold and NSCs have a good biocompatibility and biodegradablity. MHT and fibrin scaffold jointed NSCs improve neurologic function in rat TBI model with the synergistic reaction.

Key words: traumatic brain injury, neural stem cells, fibrin scaffold, mildhypothermia