| Objective:Traumatic brain injury (TBI) often causes cognitive deficits and remote symptomatic epilepsy. To observe the changes of electrophysiology in rats which were received different doses of MP treatment after traumatic brain injury. To provide theoretical foundation of rational treatment for using MP after fluid percussion injury.Methods:The study uses adult male Wistar rats (n=230) which were randomly divided into five different groups, including Normal MP treatment group (n=40), naive group (n=40), TBI group (n=50), TBI+Low-dose MP group (n=50), TBI+ High-dose MP group (n=50). Using MODEL01-B hydraulic impact instrument, we make TBI models in reference to stereotaxic coordinates of rat brain. Rats were received different treatments according to the group, after fluid percussion injury. Rats were treated to receiving MP (5 mg/kg for Low-dose and 30 mg/kg for high-dose) for treatment; rats in Normal MP Treatment group were received anesthesia, surgical procedure and MP 30 mg/kg; rats in the TBI group were received anesthesia, surgical procedure, FPI, and equal volume of saline. We observed brain injury condition in rats through MNSS, MR imaging and HE staining. Brain sections were also examined by immunocytochemistry staining to investigate the count of hippocampal interneurons. We detected the changes of spatial learning ability in rats by Morris water maze and electrophysiology in rats by LTP and I/O curves. Datas of the experiment was observed and analyzed statistically by SPSS 13.0(SPSS Inc., Chicago, IL).Results:Rats had definitely injured after impaction, we could observe Local contusion in HE-staining and MRI formed by fluid percussion injury. Histological staining revealed count changes of hippocampal interneurons, and high-dose MP treatment worsened these results in rats. We recived the data as follow:the rat FPI is a well-characterized and extensively used model of experimental TBI. After exposure to a controlled impact of 1.8-2.0 atm to the brain, there was no significant difference in mNSS between experimental groups 24 h after FPI (one-way analysis of variance [ANOVA], F(2,147)=0.838, P=0.434); The rats on high-dose MP treatment took a significantly longer time to find the platform as compared to TBI rats without MP. Such a pattern of the learning curve indicates that there was a significant difference in spatial learning disability of rats related to trauma and MP usage; In the CA1 area, one-way ANOVA analysis revealed a statistical significance among between groups (F(4,295)=1496.944, P<0.001) in LTP; In the DG area (Fig.3C), we also detected a significant difference between groups (F(4,295)=3213.130,140 P<0.001) in LTP. Using design-based stereological procedures, we detectinjury-induced interneuronal loss in the DG and CA3, but not in the CA1 subregions in the hippocampus on day 7. There are no difference between these data on day 7 and day 11 post-injury.Conclusion:The functional and electrophysiological deficits are associated with a decrease in the number of parvalbumin-immunoreactive (PV-IR) and cholecystokinin-immunoreactive (CCK-IR) GABAergic cells. The data suggest that MP therapy may decrease the number of DG interneurons in post-traumatic hippocampus, resulting in the aggravated deficits of learning ability induced by TBI. The complexity of the inhibitory changes after FPI suggests that systemic application of a drug affecting GABA activity was unlikely to be sufficient to normalize hippocampal function. Future studies should be directed toward characterization of putative regional alterations in hippocampal excitatory activity. |
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