Liraglutide Improves ?-amyloid Deposits And Secondary Damage In The Ipsilateral Thalamus After Focal Cerebral Infarction

Objective: The present study aimed to investigate the protective effects of liraglutide,a long-acting glucagon-like peptide-1(GLP-1)analogue,on A? deposits and secondary damage in ipsilateral thalamus after focal cerebral infarction.In addition,this study was conducted to investigate whether liraglutide could improve sensory function after focal cerebral infarction.Methods: Forty-two Sprague–Dawley rats were subjected to distal middle cerebral artery occlusion(MCAO)and then randomly divided into liraglutide(n = 14),vehicle(n = 14),and sham-operated(n = 14)groups.At 1 hour after MCAO,rats in the liraglutide and vehicle groups were subcutaneously injected with liraglutide(100 ?g/kg/d)and isopyknic vehicle,respectively,then continuously injected once a day for 7 days.Sensory function and secondary thalamic damage were assessed with adhesive-removal test,Nissl staining and immunostaining at 7 days after MCAO.TUNEL staining was employed to detect the neuronal apoptosis.The protein expression of Bcl-2 and Bax were measured by the method of Western blot.Results:1?At 7 days after distal MCAO,the mean time of adhesive-removal at left forepaw in the vehicle and liraglutide groups significantly increased compared with the sham-operated group(All P < 0.001).liraglutide decreased the mean time of adhesive-removal at left forepaw compared with the vehicle group(P < 0.05).2?Compared with sham-operated group,abnormal A? deposition was observed in the ipsilateral thalamus in the vehicle and liraglutide groups at 7 days after MCAO.Treatment with liraglutide markedly reduced A? deposition compared with that in the vehicle group(P < 0.05).3?Compared with sham-operated group,the number of intact neurons in the ipsilateral thalamus of the liraglutide and vehicle groups was notably decreased at 7 days post-MCAO.The glial fibrillary acidic protein(GFAP)-positive area and the number of ionized calcium binding adaptor molecule-1(Iba-1)-positive cells in the ipsilateral thalamus of the vehicle and liraglutide groups were markedly increased compared with the sham-operated group at 7 days after MCAO(All P < 0.05).Liraglutide treatment significantly improved the number of intact neurons compared with vehicle group(P < 0.05).Liraglutide significantly decreased the GFAP-positive area and the number of Iba-1-positive cells compared with the vehicle group(All P < 0.05).4?Compared with sham-operated group,the number of TUNEL-positive neurons in the ipsilateral thalamus of vehicle and liraglutide groups were significantly increased(All P < 0.05).Liraglutide significantly decreased the number of TUNEL-positive neurons in the ipsilateral thalamus compared with the vehicle group at 7 days after MCAO(P < 0.05).Liraglutide markedly increased the levels of Bcl-2 and reduced the levels of Bax compared with the vehicle group at 7 days after MCAO(P < 0.05).Conclusions: These results suggest that liraglutide reduces A? deposits in the ipsilateral thalamus,and improves the secondary thalamic damage after focal cerebral infarction.Moreover,liraglutide improves the sensory impairment in rats after focal cerebral infarction.