Liraglutide Ameliorates β-Amyloid Deposits and Secondary Damage in the Ipsilateral Thalamus and Sensory Deficits After Focal Cerebral Infarction in Rats.

Hui-Li Zhu,Ying Zhao,Zhang-Pei Liu,Da-Wei Dong,Wan-Yong Yang,An-Ding Xu,Bing Yang,Li-An Huang,Yu-Sheng Zhang

doi:10.3389/fnins.2018.00962

Abstract

Focal cerebral infarction causes β-amyloid (Aβ) deposition and secondary neuronal degeneration in the ipsilateral thalamus. Thalamus is the subcortical center of sensory, the damage of thalamus could cause sensory deficits. The present study aimed to investigate the protective effects of liraglutide, a long-acting glucagon-like peptide-1 (GLP)-1 receptor agonist, on Aβ deposits and secondary damage in the ipsilateral thalamus after focal cerebral infarction. In addition, this study was conducted to investigate whether liraglutide could improve sensory function after focal cerebral infarction. Forty-two male Sprague–Dawley rats were subjected to distal middle cerebral artery occlusion (MCAO) and then randomly divided into liraglutide and vehicle groups, and 14 sham-operated rats as control. At 1 h after MCAO, rats in the liraglutide and vehicle groups were subcutaneously injected with liraglutide (100 μg/kg/d) and isopyknic vehicle, respectively, once a day for 7 days. Sensory function and secondary thalamic damage were assessed using adhesive-removal test and Nissl staining and immunostaining, respectively, at 7 days after MCAO. Terminal deoxynucleotidyl transferase 2’-deoxyuridine 5’-triphosphate nick end labeling and Western blot were used to detect neuronal apoptosis. The results showed that liraglutide improved sensory deficit compared to the controls. Liraglutide treatment significantly reduced Aβ deposition compared with the vehicle treatment. Liraglutide treatment decreased the neuronal loss, astroglial and microglial activation, and apoptosis compared with the vehicle treatment. Liraglutide significantly down-regulated the expression of Bcl-2 and up-regulated that of Bax in the ipsilateral thalamus compared with the vehicle group. These results suggest that liraglutide ameliorates the deposition of Aβ and secondary damage in the ipsilateral thalamus, potentially contributing to improve sensory deficit after focal cerebral infarction.

Highlights

Focal cerebral infarction after distal middle cerebral artery occlusion (MCAO) causes the primary cortical infarction, and results in secondary damage in the regions that have synaptic connections with the primary ischemic lesion (Zhang et al, 2012)
This study aimed to investigate that the effects of liraglutide on Aβ deposits, apoptosis and secondary damage in the ipsilateral thalamus after focal cerebral infarction in rats
At 7 days after MCAO, the mean time to remove the stimulus from the left forepaw increased significantly in liraglutide and vehicle groups compared with the control group (28.1 ± 3.1 and 40.6 ± 4.6 vs. 7.4 ± 0.8 seconds, all P < 0.001)

Summary

Introduction

Focal cerebral infarction after distal middle cerebral artery occlusion (MCAO) causes the primary cortical infarction, and results in secondary damage in the regions that have synaptic connections with the primary ischemic lesion (Zhang et al, 2012). The most common secondary damage is ipsilateral thalamic degeneration after cerebral infarction, including neuronal loss, gliosis, axonal degeneration, hyperphosphorylation of Tau protein, and β-amyloid (Aβ) deposits (Dong et al, 2014; Xing et al, 2014). Such thalamic damage leads to delayed neuronal recovery (Baumgartner et al, 2018). The GLP1R agonists have been found to exert neuroprotective effects against neurodegeneration and cerebral ischemic injury (Kuroki et al, 2016; Batista et al, 2018; Kabel et al, 2018)

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