Lixisenatide Reduced Damage in Hippocampus CA1 Neurons in a Rat Model of Cerebral Ischemia-Reperfusion Possibly Via the ERK/P38 Signaling Pathway

Gad, Salma N; Nofal, Shahira; Raafat, Eman; Ahmed, Ashraf M.

doi:10.1007/s12031-020-01497-9

Cited by 13 publications

(21 citation statements)

References 60 publications

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“…Two studies investigated multiple doses of GLP-1RAs to compare neuroprotective efficacy and concluded that neuroprotection was dose-dependent. 20 , 51…”

Section: Resultsmentioning

confidence: 99%

“…Conversely, Bax is a pro-apoptotic protein and increases cytochrome C levels. 52 Increased Bcl-2 and reduced Bax levels, contributing to an increased Bcl-2:Bax ratio and representing reduced levels of apoptosis, have been reported in 3 studies of liraglutide 29,33,37 and 1 study for each pro-GLP-1, 45 rhGLP-1, 39 DMB, 22 Ex-4, 50 Lixisenatide, 51 GLP-1/GIP DA 47 and semaglutide. 43 Critically, this reduction of apoptosis was reproduced in normoglycemic models when administered after stroke onset.…”

Section: Cellular Functionmentioning

confidence: 93%

“…54 Liraglutide, Exendin-4, Lixisenatide, rhGLP-1 and semaglutide have been shown to reduce levels of caspase-3 in pre-clinical models of stroke. 33,37,39,[41][42][43]46,50,51 Zhu et al have also demonstrated reduced levels of caspase 8 and 9 in models administered liraglutide. 33 Cleavage of PARP by caspases is a signal of apoptosis and has been implicated in cerebral ischemia.…”

Section: Cellular Functionmentioning

confidence: 99%

“…20 Reduced levels of other markers of inflammation, such as myeloperoxidase and interleukin, have also been reported. 30,37,51 One study reported a non-statistically significant reduction in pro-inflammatory markers. 25 There is also deterioration in markers of oxidative stress following AIS.…”

Section: Cellular Functionmentioning

confidence: 99%

“…19,[21][22][23]41,45,46,49 Two studies investigated multiple doses of GLP-1RAs to compare neuroprotective efficacy and concluded that neuroprotection was dose-dependent. 20,51 Most studies administered GLP-1RAs via intraperitoneal, subcutaneous or transvenous routes. However, Zhang et al reported neuroprotection with both oral DMB 46 and intranasal exendin-4.…”

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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

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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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“…Two studies investigated multiple doses of GLP-1RAs to compare neuroprotective efficacy and concluded that neuroprotection was dose-dependent. 20 , 51…”

Section: Resultsmentioning

confidence: 99%

Section: Cellular Functionmentioning

confidence: 93%

Section: Cellular Functionmentioning

confidence: 99%

Section: Cellular Functionmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

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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miR‐23b/TAB3/NF‐κB/p53 axis is involved in hippocampus injury induced by cerebral ischemia–reperfusion in rats: The protective effect of chlorogenic acid

et al. 2022

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Apoptosis is the main pathological aspect of neuronal injury after cerebral ischemia–reperfusion (I/R) injury. However the detailed molecular mediators are still under debate. The aim of this study is to explore the effect of cerebral I/R on miR‐23a/TGF‐β‐activated kinase 1 binding protein 3 (TAB3)/nuclear factor kappa B (NF‐κB)/p53 axis in rat hippocampus alone and in combination with chlorogenic acid (CGA). Common carotid artery occlusion (CCAO) was performed by nylon monofilament for 20 min to establish a model of ischemic brain injury. CGA (30 mg/kg) was administered intraperitoneally (ip), 10 min prior to ischemia and 10 min before reperfusion. Examination of hippocampus neurons by terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling staining showed that the number of apoptotic neurons was elevated at 24 h after reperfusion. At the molecular levels, I/R injury resulted in an increased protein expression of p53 with a concomitant upregulation of cleaved‐caspase3/phosphorelated‐caspase3 ratio and cytochrome c level. Further miR‐23b gene expression was significantly downregulated after 24 h of reperfusion. Also, we observed increased TAB3 and NF‐κB protein expressions after 24 h following CCAO. Treatment with CGA significantly reduced the apoptotic damage and also reversed miR‐23b gene expression, TAB3 and NF‐κB protein expressions in hippocampus neurons in I/R rats. In conclusion our data suggest that miR‐23b/TAB3/NF‐κB/p53 axis could play a regulatory role in hippocampus cell death, which provide a new target for novel therapeutic interventions during transit ischemic stroke. It also demonstrated that CGA could reverse these molecular alterations indicating an effective component against hippocampus apoptotic insult following acute I/R injury.

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Mfsd2a attenuated hypoxic-ischemic brain damage via protection of the blood–brain barrier in mfat-1 transgenic mice

Zhang

Chang

et al. 2023

Cell. Mol. Life Sci.

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Previous studies have shown that mfat-1 transgenic mice have protective effects against some central nervous system (CNS) disorders, owing to the high docosahexaenoic acid (DHA) content enriched in their brains. However, whether this protective effect is connected to the blood–brain barrier (BBB) remains unclear. This study aims to investigate the mechanisms of the protective effect against hypoxic-ischemic brain damage (HIBD) of mfat-1 transgenic mice. mfat-1 mice not only demonstrated a significant amelioration of neurological dysfunction and neuronal damage but also partly maintained the physiological permeability of the BBB after HIBD. We initially showed this was associated with elevated major facilitator superfamily domain-containing 2a (Mfsd2a) expression on the BBB, resulting from more lysophosphatidylcholine (LPC)-DHA entering the brain. Wild-type (WT) mice showed a similar Mfsd2a expression trend after long-term feeding with an LPC-DHA-rich diet. Knockdown of Mfsd2a by siRNA intra-cerebroventricular (ICV) injection neutralized the protective effect against HIBD-induced BBB disruption in mfat-1 mice, further validating the protective function of Mfsd2a on BBB. HIBD-induced BBB high permeability was attenuated by Mfsd2a, primarily through a transcellular pathway to decrease caveolae-like vesicle-mediated transcytosis. Taken together, these findings not only reveal that mfat-1 transgenic mice have higher expression of Mfsd2a on the BBB, which partly sustains BBB permeability via vesicular transcytosis to alleviate the severity of HIBD, but also suggest that dietary intake of LPC-DHA may upregulate Mfsd2a expression as a novel therapeutic strategy for BBB dysfunction and survival in HIBD patients.

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Lixisenatide Reduced Damage in Hippocampus CA1 Neurons in a Rat Model of Cerebral Ischemia-Reperfusion Possibly Via the ERK/P38 Signaling Pathway

Cited by 13 publications

References 60 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

miR‐23b/TAB3/NF‐κB/p53 axis is involved in hippocampus injury induced by cerebral ischemia–reperfusion in rats: The protective effect of chlorogenic acid

Mfsd2a attenuated hypoxic-ischemic brain damage via protection of the blood–brain barrier in mfat-1 transgenic mice

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