Effects Of Ganglioside And Mild Hypothermia Combined Theraphy In Traumatic Brain Injury (TBI) Rats And Related Mechnisms

Objective:To investigate the protective effects of ganglioside and hypothermia combined treatment on traumatic brain injury in rats. Methods:The experiment contains two parts. According to the different observation time, rats were randomly divided into different experiments. 100 male SD rats, weight 220~260g, were randomly divided into 5 groups of TBI model: sham group(Group S), control treatment group(Group C), mild hypothermia treatment group(Group MHT), ganglioside treatment group(Group GM) and combined MHT and GM group(Group MHT+GM). On the one hand,This experiment was used to identify the Neuro—protective effects of mild hypothermia(MHT) and ganglioside therapy, on the other hand,it could evaluate the effects of mild MHT and GM therapy on the expression of NO, MDA, BBB, Cyt C and caspase-3 in traumatic brain injury brain. The first experiment, at36-48 h, the capacity of study and memory were evaluated by water maze test. Neurological deficit was evaluated to use a modified neurological severity score(m NSS) and head MRI was examined after 48 h FPI. The content of brain water and permeability of blood-brain barrier were contected. The second experiment, fifty male rats were randomly divided into five groups. All TBI rats were decapitated after 48 h, the content of MDA, NO and Cyt C were measured by detection kits, Western blotting was used to analyze the expression of caspase-3. Results:1 The capacity of study and memory: The result of the capacity: Compared with Group C, Group MHT, Group GM, Group MHT+GM all get better result of nerve functional defect(P<0.05), while it seems that MHT with GM treatment has the best effect(P<0.05).2 The result of neurological deficit: Compared with Group C, Group MHT, Group GM, Group MHT+GM get better result(P<0.05), while it seems that the effect of MHT+GM treatment is the best(P<0.05).3 Brain water content measurement: Compared with Group S, brain water content of Group C was significantly increased; Compared with Group C, the brain water content of Group MHT, Group GM, Group MHT+GM were lower(P < 0.05); Compared with Group MHT and Group GM, the brain water content of Group MHT+GM was better(P<0.05).4 The permeability of blood-brain barrier measurement: Compared with Group C, the blood brain barrier in Group MHT, Group GM and Group MHT+GM was worse according to the Evans-blue test(P<0.05), compared with Group MHT and Group GM in changing the permeability of blood-brain barrier, Group MHT+GM treatment has the best effect(P<0.05) in blood-brain barrier.5 The results of MRI: the MRI of Group C showed brain damage in the cortical and subcortical regions, a severe astrocytic reaction in the area surrounding the lesion; Compared with Group C, Group MHT, Group GM and Group MHT+GM attenuate the impairment of cortical and subcortical regions,with slight astrocytic reaction in the area surrounding the lesion.6 NO and MDA: Compared with Group S, the No and MDA levels were significantly increased in TBI groups(P<0.05). The level of No and MDA was significantly reduced in Group MHT, Group GM, Group MHT+GM compared with Group C(P<0.05). The No and MDA level in Group MHT and Group GM was higher than in Group MHT+GM(P<0.05).7 Caspase-3: Compared with Group C, Caspase-3 protein levels by western blot assays of the brain were significantly reduced. The expression of Caspase-3 was significantly decreased in Group MHT, Group GM, Group MHT+GM. Compared with Group MHT and Group GM, Group MHT+GM can reduce the expression of Caspase-3 regularly.8 Cyt C: Compared with Group S, the level of cyt C in cytoplasm was lower in the Group C,Group MHT, Group GM and Group MHT+GM, while it was higher in mitochondrion than in Group C, Group MHT, Group GM and Group MHT+GM. Compared with Group C, the level of cyt C was higher in cytoplasm than in the Group MHT, Group GM and Group MHT+GM, while it was lower in mitochondrion than in Group C,Group MHT, Group GM and Group MHT+GM.(P<0.01) Conclusion:Ganglioside and/or mild hypothermia have protective effects on TBI in rats,which can rise the capacity of study and memory, reduce neurological deficit scores and lessen brain water content, reduce the permeability through the blood brain barrier,especially when ganglioside and mild hypothermia are used simultaneously.The protective effects on traumatic brain injury(TBI)in rats were probably associated with ROS/cytochrome C/capase-3 signaling activation. So ganglioside and hypothermia combined treatment would be one more way for traumatic brain injury therapy.