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

Abstract

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.

Empagliflozin reduces vascular damage and cognitive impairment in a mixed murine model of Alzheimer’s disease and type 2 diabetes

“…A similar profile was observed in the hippocampus, and microglia burden was reduced after EMP treatment in SP-free areas (close to plaques ([F (3,39) =2.21, p = 0.91]); far from plaques [F (7, 768) = 23.79, ╫╫ p < 0.01 vs. control, control-EMP, APP/ PS1, APP/PS1-EMP, and APP/PS1xdb/db-EMP, † † p < 0.01 vs. control, control-EMP, APP/PS1-EMP, and APP/PS1xdb/db-EMP, ♯♯ p < 0.01 vs. control and control-EMP]) (control n = 5, control-EMP n = 5, APP/PS1 n = 5, APP/PS1-EMP n = 4, db/db n = 6, db/db-EMP n = 4, APP/PS1xdb/db n = 4, APP/ PS1xdb/db-EMP n = 5). density after long-term administration, as previously described with other antidiabetic treatments [12,35,36]. Vascular disease has been closely associated to AD and T2D, and a synergistic effect has been reported when both pathologies coexist.…”

Root of Angelica gigas Nakai ameliorates ischemic stroke-induced brain injury in mice through the activation of the PI3K/AKT/mTOR and MAPK pathways

“…There have been many reports that SIRT1 can be a target of herbal medicines [30]. However, in this study neither tMCAO or the pre-administration of AGmex had any effect on SIRT1 expression ( Fig.…”

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

“…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:…”

“…However, whilst there are some reports of Ex-3-9 administration blocking neuroprotection, 21 suggestive of GLP-1R dependence, other studies did not demonstrated this trendhighlighting the possibility of a GLP-1R independent mechanism 41,46. For example, GLP-1[28][29][30][31][32][33][34][35][36] is cleaved from endogenous GLP-1; research has shown this cell-permeable nonapeptide to have antioxidant, anti-apoptotic and mitochondrial regulatory properties in pancreatic cellsfurther research is required to establish its role in neural tissue59 .…”