Effect of temperature sensitive umbilical cord mesenchymal stem cell therapy combined with mild hypothermia on cognitive function in rats of severe traumatic brain injury

Objective To investigate the effect of temperature sensitive umbilical cord mesenchymal stem cells (tsUCMSCs) transplantation under mild hypothermia environment on cognitive function of rats after severe traumatic brain injury (TBI).Methods Thirty-six male SD rats weighing (300 ± 20)g were subjected to severe TBI by fluid percussion device (2.5 atm) and managed with tsUCMSCs combined with mild hypothermia.Rats were divided into three groups:sham operation group,TBI group,and TBI + tsUCMSCs + mild hypothermia group (TBI + intervention group) according the random number table,with 12 rats per group.Latency to the platform and the time in targeted quadrant were recorded to evaluate the learning and memory with Morris water maze.Population spike (PS) and excitatory postsynaptic potential (EPSP) of long-term potential (LTP) were examined to evaluate synaptic plasticity of hippocampus.Phosphorylated Tau at Thr231 and phosphorylated GSK3 at Ser9 were detected by Western blot.Results Latency to the platform [(15.9 ±3.2) s vs (8.08 ±2.69) s,P＜0.01]was prolonged and time in targeted quadrant [(14.4 ± 3.0) s vs (36.3 ± 5.7) s,P ＜ 0.01] was shortened in TBI group at day 28 compared with sham operation group.Whereas,latency to the platform [(10.7 ± 2.8) s,at Ser9 were detected by Western blot.Results Latency to the platform [(15.9 ± 3.2) s vs (8.08 ± 2.69) s,P ＜ 0.01] was prolonged and time in targeted quadrant [(14.4 ± 3.0) svs (36.3 ± 5.7) s,P ＜0.01] was shortened in TBI group at day 28 compared with sham operation group.Whereas,latency to the platform [(10.7 ± 2.8) s,P ＜ 0.01] and time in targeted quadrant [(29.4 ± 4.4) s,P ＜ 0.05 |were reversed in TBI + intervention group.PS and EPSP of LTP were elevated in TBI group,but the elevation was suppressed in TBI + intervention group.Meanwhile,Tau hyperphosphorylation (0.80 ± 1.00vs 1.24 ±0.13,P＜0.05) and GSK3 deactivation (3.01 ±0.41 vs 1.27 ±0.22,P ＜0.01) were significantly reversed in TBI + intervention group compared with TBI group.Conclusion Combination of tsUCMSCs and mild hypothermia therapy can improve the TBI-induced cognitive deficit. Key words: Craniocerebral trauma;  Stem cells ;  Cognition ;  Mild hypothermia