Delayed Administration of the Glucagon-Like Peptide 1 Analog Liraglutide Promoting Angiogenesis after Focal Cerebral Ischemia in Mice

Chen, Yanxia; Zhang, Xiangjian; He, Jianbin; Xie, Yanzhao; Yang, Yang

doi:10.1016/j.jstrokecerebrovasdis.2017.12.015

Cited by 24 publications

(30 citation statements)

References 39 publications

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“…Liraglutide was associated with a reduction in infarct volume when the first dose was delayed by up to 1 day. 35 Kim et al reported a reduction in infarct volume by up to 75% in a rat model of transient MCAO. Darsalia et al reported that Exendin-4 administration was associated with a reduction in stroke volume when administered for 4 weeks prior to, and 2-4 weeks following stroke onset.…”

Section: Infarct Volume and Neuronal Survivalmentioning

confidence: 98%

“…43 Nine studies reported a reduction in neurological deficit when GLP-1RAs were administered to normoglycemic models at least 1 hour after induction of AIS. [32][33][34][35][36]41,43,47,49 Notably, Filchenko et al reported that whilst reduction in neurological deficit was observed in the non-diabetic rat model treated with liraglutide, this trend was not observed in the diabetic groups. 31 Potential mechanisms:…”

Section: Neurological Outcomesmentioning

confidence: 99%

“…This is to be expected as GLP-1RA associated insulin secretion from the pancreas is glucose dependent. 35 Indeed, Zhang et al concluded that neuroprotection was not glucose dependent. 45 Yang et al monitored blood glucose in rats which underwent intraperitoneal administration of semaglutide starting 2 hours following unilateral permanent MCAO occlusion, further demonstrating neuroprotection in the absence of hypoglycemic episodes.…”

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confidence: 99%

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Glucagon-like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke: a systematic scoping review

Maskery

Hölscher

Jones

et al. 2020

J Cereb Blood Flow Metab

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Stroke mortality and morbidity is expected to rise. Despite considerable recent advances within acute ischemic stroke treatment, scope remains for development of widely applicable neuroprotective agents. Glucagon like peptide-1 receptor agonists (GLP-1RAs), originally licensed for the management of Type 2 Diabetes Mellitus, have demonstrated pre-clinical neuroprotective efficacy in a range of neurodegenerative conditions. This systematic scoping review reports the pre-clinical basis of GLP-1RAs as neuroprotective agents in acute ischemic stroke and their translation into clinical trials. We included 35 pre-clinical studies, 11 retrospective database studies, 7 cardiovascular outcome trials and 4 prospective clinical studies. Pre-clinical neuroprotection was demonstrated in normoglycemic models when administration was delayed by up to 24 h following stroke induction. Outcomes included reduced infarct volume, apoptosis, oxidative stress and inflammation alongside increased neurogenesis, angiogenesis and cerebral blood flow. Improved neurological function and a trend towards increased survival were also reported. Cardiovascular outcomes trials reported a significant reduction in stroke incidence with semaglutide and dulaglutide. Retrospective database studies show a trend towards neuroprotection. Prospective interventional clinical trials are on-going, but initial indicators of safety and tolerability are favourable. Ultimately, we propose that repurposing GLP-1RAs is potentially advantageous but appropriately designed trials are needed to determine clinical efficacy and cost-effectiveness.

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Section: Infarct Volume and Neuronal Survivalmentioning

confidence: 98%

Section: Neurological Outcomesmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Glucagon-like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke: a systematic scoping review

Maskery

Hölscher

Jones

et al. 2020

J Cereb Blood Flow Metab

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“…Both experimental studies and large randomized trials have indicated that the treatment with stable GLP-1 analogues, both before and after onset of ischemic stroke, may be neuroprotective and may reduce the risk of ischemic stroke [12][13][14][15][16][17][18]. Protection from stroke by GLP-1 analogues was also recently shown in a metaanalysis by Barkas [19].…”

Section: Introductionmentioning

confidence: 93%

“…Experimental animal studies have also shown that acute treatment with GLP-1 analogues and dipeptidyl peptidase-4 (DPP-4) inhibitors after a stroke is neuroprotective including better recovery [12,35,36], as recently reviewed [37][38][39]. Treatment with the GLP-1 analogue liraglutide after experimental stroke has been shown to promote angiogenesis and to improve functional outcome [18]. However, there are to date no clinical studies that have examined neuroprotective effects of neither endogenous nor pharmacologically administered GLP-1 in mitigating the impact of a stroke in humans [20].…”

Section: Effects Of Glp-1 On the Cardiovascular Systemmentioning

confidence: 99%

GLP-1 secretion in acute ischemic stroke: association with functional outcome and comparison with healthy individuals

Larsson

Patrone

Euler

et al. 2019

Cardiovasc Diabetol

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Background Glucagon-like peptide-1 (GLP-1) treatment has been shown to reduce stroke incidence in diabetes and also to be neuroprotective in experimental stroke models. The prognostic value of endogenous levels of GLP-1 in the recovery phase after stroke remains to be elucidated. The aim of the study was to investigate the potential association between GLP-1 levels and functional outcome after stroke and to determine whether GLP-1 is altered in the acute phase of stroke compared to 3 months post stroke and to healthy controls. Methods Fasting GLP-1 was measured on hospital day 2–4 in patients without previously known diabetes (n = 59) that received recombinant tissue plasminogen activator (rtPA) for ischemic stroke. Fasting GLP-1 was measured again after 3 months and neurologic outcome was measured as modified Rankin Scale (mRS). mRS ≥ 2 was considered as unfavorable outcome. A control group of healthy individuals (n = 27) was recruited and their fasting GLP-1 was measured. Results Fasting GLP-1 was higher in the patients that suffered a stroke compared to healthy controls (25.1 vs. 18.0 pmol/L; p = 0.004). The GLP-1 levels did not change significantly at the 3-month follow up OGTT (25.8 vs. 25.6; p = 0.80). There was no significant association between GLP-1 levels and unfavorable mRS (OR 1.03, 95% CI 0.95–1.12, p = 0.50). Conclusions Endogenous GLP-1 levels in patients that recently suffered an ischemic stroke are higher than in healthy controls and remained unchanged at the 3 months follow-up, possibly indicating an elevation of the levels of GLP-1 already pre-stroke. However, no association between endogenous GLP-1 and functional outcome of stroke 3 months post stroke was found.

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Role of liraglutide in brain repair promotion through Sirt1‐mediated mitochondrial improvement in stroke

Wang

Zhao

et al. 2019

Journal Cellular Physiology

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Brain repair, especially axonal sprouting, is critical to restore motor function in disabled stroke patients. Liraglutide (LG) is a new kind of long-acting analogue of glucagon-like peptide-1 (GLP-1) and has potential protective effects in stroke. The mitochondria participate in brain repair after cerebral injury. However, the mechanism of the effect of LG on brain repair and its potential influence on mitochondria in stroke remains obscure. Here, in focal cerebral cortical ischemic mice model, LG improved the motor functional recovery and promoted axonal sprouting by restoring the activities of isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, and succinate dehydrogenase. Moreover, LG remarkably increased the cell survival rate and revived the NeuN and GAP-43 levels in cortical neurons under hydrogen peroxide (H 2 O 2 ) exposure. It was also observed that LG reduced the generation of reactive oxygen species, stabilized the mitochondrial membrane potential, enhanced the levels of adenosine triphosphate, enhanced activities of mitochondrial complex-I, and decreased protein expression levels of fission-1 in H 2 O 2 -injured cortical neurons.Additionally, LG suppressed the expressions of sirtuin 1 (Sirt1) in cortical neurons exposed to H 2 O 2 . Furthermore, knockdown of Sirt1 by short interfering RNA facilitated the LG-mediated mitochondrial protection in cortical neurons under H 2 O 2 .Collectively, this data from the present study illustrated that LG exerted a promoting influence on brain repair, after cerebral ischemic injury, through Sirt1-mediated mitochondrial improvement.

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Delayed Administration of the Glucagon-Like Peptide 1 Analog Liraglutide Promoting Angiogenesis after Focal Cerebral Ischemia in Mice

Cited by 24 publications

References 39 publications

Glucagon-like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke: a systematic scoping review

Glucagon-like peptide-1 receptor agonists as neuroprotective agents for ischemic stroke: a systematic scoping review

GLP-1 secretion in acute ischemic stroke: association with functional outcome and comparison with healthy individuals

Role of liraglutide in brain repair promotion through Sirt1‐mediated mitochondrial improvement in stroke

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