Neuroprotective and anti-apoptotic effects of liraglutide in the rat brain following focal cerebral ischemia

Briyal, Seema; Shah, Sadia; Gulati, Anil

doi:10.1016/j.neuroscience.2014.09.064

Cited by 91 publications

(88 citation statements)

References 76 publications

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“…This effect is crucial since obesity increases the susceptibility to neurodegenerative diseases. Although these beneficial protective effects of liraglutide were reported in other experimental models of disease, like cerebral ischemia, Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases , an original finding of the present study is the stimulation of an anti‐apoptotic pathway in the ARC nucleus of diet‐induced obesity.…”

Section: Discussionmentioning

confidence: 68%

Effects of liraglutide in hypothalamic arcuate nucleus of obese mice

Barreto-Vianna

Águila

Mandarim-de-Lacerda

2016

Obesity

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Objective: The neuroprotective effects of liraglutide (200 lg/kg, twice daily, subcutaneous administration) in the hypothalamic arcuate nucleus (ARC) of diet-induced obese mice were investigated. Methods: C57BL/6 mice were separated into groups: standard chow treated with vehicle or liraglutide and the respective liraglutide pair-fed group; high-fat diet treated with vehicle or liraglutide and the respective pair-fed group. Body mass (BM) evolution, carbohydrate metabolism, leptin resistance, proteins involved in energetic balance, apoptosis, and microglia in the ARC were studied. Results: Obese animals showed glucose intolerance, resistance to insulin and to anorexigenic effect of leptin, and microgliosis accompanied by elevated Bax/Bcl2 ratio in the ARC. Liraglutide improved the carbohydrate metabolism, BM loss, and the activation of pro-opiomelanocortin (POMC) and cocaine and amphetamine-regulated transcript (CART) in the ARC. The liraglutide enhanced leptin sensitivity and diminished the microgliosis with decrease in Bax/Bcl2 ratio. Conclusions: Liraglutide activates central anorexigenic pathways, thereby diminishing the energy intake of obese mice and improving the metabolic parameters related to obesity. Liraglutide is a relevant neuroprotective agent, which can decrease the microgliosis and stimulate the anti-apoptotic pathway, a significant effect in the treatment of obesity and its comorbidities. Some benefits of liraglutide are independent of the BM loss, which usually accompanies the drug administration.

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Section: Discussionmentioning

confidence: 68%

Effects of liraglutide in hypothalamic arcuate nucleus of obese mice

Barreto-Vianna

Águila

Mandarim-de-Lacerda

2016

Obesity

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“…Recently, studies have reported that liraglutide exhibited neuroprotection against the damage of cerebral ischaemia1112. For example, Gulati et al performed animal studies with the intraperitoneal injection of 50 μg/kg per day liraglutide for 14 days before middle cerebral artery occlusion (MCAO) surgery.…”

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confidence: 99%

The Neuroprotection of Liraglutide Against Ischaemia-induced Apoptosis through the Activation of the PI3K/AKT and MAPK Pathways

Zhu

Zhang

Shi

et al. 2016

Sci Rep

148

118

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Glucagon-like peptide-1 (GLP-1) is an incretin hormone that increases glucose-dependent insulin secretion to reduce the glucose level. Liraglutide, a long-acting GLP-1 analogue, has been found to have neuroprotective action in various experimental models. However, the protective mechanisms of liraglutide in ischaemic stroke remain unclear. Here, we demonstrated that liraglutide significantly decreased the infarct volume, improved neurologic deficits, and lowered stress-related hyperglycaemia without causing hypoglycaemia in a rat model of middle cerebral artery occlusion (MCAO). Liraglutide inhibited cell apoptosis by reducing excessive reactive oxygen species (ROS) and improving the function of mitochondria in neurons under oxygen glucose deprivation (OGD) in vitro and MCAO in vivo. Liraglutide up-regulated the phosphorylation of protein kinase B (AKT) and extracellular signal-regulated kinases (ERK) and inhibited the phosphorylation of c-jun-NH2-terminal kinase (JNK) and p38. Moreover, the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and/or the ERK inhibitor U0126 counteracted the protective effect of liraglutide. Taken together, these results suggest that liraglutide exerts neuroprotective action against ischaemia-induced apoptosis through the reduction of ROS and the activation of the PI3K/AKT and mitogen-activated protein kinase (MAPK) pathways. Therefore, liraglutide has therapeutic potential for patients with ischaemic stroke, especially those with Type 2 diabetes mellitus or stress hyperglycaemia.

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“…Moreover, by TUNEL assay, we observe that pterostilbene reduces DNA fragmentation, which is a terminal stage of apoptotic DNA degradation in the ischemic penumbra 24 h after I/R. Oxidative stress and apoptotic cell death, especially at the infarct boundary, play important roles in the development of infarct volume (Briyal et al, 2014). Accordingly, we found that pterostilbene reduced infarct volume.…”

Section: Discussionmentioning

confidence: 61%