Effects Of Dexmedetomidine On Hippocampal Inflammation In Rats With Postoperative Cognitive Dysfunction

Part I Establishment of the rat model with post operative cognitive dysfunctionObjective To establish the postoperative cognitive dysfunction model.Methods Fifty-four18months old male SD rats weighing500-600g were randomly divided into3groups:control group (group C, n=18), anaesthesia group(group A, n=18) and surgery group(group S, n=18). Rats in group C did not receive anesthesia and surgery. Rats in group A were administered with1.5-2%isoflurane. Rats in group S received partial hepatectomy under isoflurane anesthesia. Cognitive function was assessed using Y maze test on the1st,3rd and7th day after surgery.Results There was no significant difference in the number of arm entries in all groups (P>0.05). Compared with group C, the alternation score%was significantly decreased in group S on1st and3rd day after anesthesia and surgery (P <0.05). There was no significant difference between groupC and groupA in alternation score%(P>0.05).Conclusions The POCD model was established successfully via partial hepatectomy in aged rats. Part II The changes of inflammatory reaction in the hippocampus of the POCD ratsObjective To investigate the changes of inflammatory response in the hippocampus of POCD rats.Methods Thirty-six18months old male SD rats weighing500-600g were randomly divided into2groups:control group (group C, n=18) and surgery group(group S, n=18). Rats in group C did not receive anesthesia and surgery. Rats in group S received partial hepatectomy under isoflurane anesthesia.On postoperative day1,3and7,rats were euthanised to assess the expression of TNF-α、IL-1β and NF-κB p65in the hippocampus.Results Compared with group C,the expression of TNF-α、IL-1β and NF-κB p65in group S increased significantly on postoperative day1and3.There was no significant difference between group C and group S for aforementioned inflammatary molecule expressions on postoperative day7.Conclusions A short-term inflammatory response was detected in POCD rats. Part Ⅲ Effects of dexmedetomidine on hippocampal inflammatory response and cognitive function in the POCD ratsObjective To investigate the effects of dexmedetomidine on hippocampal inflammatory response and cognitive function in the POCD rats.Methods Seventy-two male Sprague Dawley rats weighing500-600g were randomly assigned into4groups:control group(group C),surgery group(group S), low-dose group(group LD) and high-dose group(group HD).Rats in group C did not receive anesthesia and surgery; rats in group S received partial hepatectomy under isoflurane anesthesia; rats in group LD and HD were subjected to similar anesthesia and surgery as the group S.Besides,rats in these group were administered with dexemedetomidine intraperineal1h after the surgery(10μg/kg for LD and30μg/kg for HD).On postoperative day1,3and7,rats were subjected to Y-maze to evaluate the cognitive function.Afterwards,rats were euthanised to assess the expression of TNF-α、IL-1β and NF-κB p65in hippocampus.Results1.There was no significant difference in number of arm entries among4groups.2.On postoperative day1and3, the alternation score%of dexmedetomidine treatment group(group LD and group HD) increased significantly,when compared to group S.3.Compared with group S, the hippocampal expressions of TNF-α、IL-1β and NF-κB p65decreased significantly on postoperative day1and3.Conclusions Dexmedetomidine inhibits hippocampal inflammation and improves cognitive impairment in aged rats following partial hepatectomy, which may be associated with down-regulation of NF-κBp65expression in the hippocampus.