Neuroprotective potential of glibenclamide is mediated by antioxidant and anti-apoptotic pathways in intracerebral hemorrhage

Zhou, Fangfang; Liu, Yangjun; Yang, Baofeng; Hu, Zhiping

doi:10.1016/j.brainresbull.2018.06.006

Cited by 28 publications

(32 citation statements)

References 35 publications

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“…Glibenclamide, a Sur1-Trpm4 inhibitor and hypoglycemic agent, has shown promising results in ischemic and hemorrhagic stroke, including reducing edema, mortality, and functional deficits [12,14,16,17]. In contrast to those findings, glibenclamide did not reduce BBB permeability, element concentration alterations, edema, behavioral impairment or brain injury after collagenase-induced ICH in our experiments.…”

Section: Discussioncontrasting

confidence: 87%

“…This suggests that glibenclamide may worsen injury after hemorrhage, but we note that we are underpowered to detect an effect of this size. Unfortunately, other ICH studies did not examine lesion size, so we do not know if this effect occurred in those experiments [16,17]. No other study of glibenclamide in ICH has quantified lesion volume or total tissue loss (including cell death, cavity formation, and ventriculomegaly), which is an accepted and unambiguous measure of neuroprotection [25].…”

Section: Discussionmentioning

confidence: 99%

“…Jiang et al used the autologous whole blood model of ICH in Sprague Dawley rats, and found glibenclamide reduced edema, protected blood-brain barrier (BBB) integrity, and improved long-term neurological deficits [16]. Another study, using the collagenase model of ICH in rats, reported that glibenclamide reduced oxidative stress, inhibited apoptosis, and improved neurological deficits [17]. Neither of these studies measured ion concentrations nor did they assess lesion size.…”

Section: Introductionmentioning

confidence: 99%

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Glibenclamide, a Sur1-Trpm4 antagonist, does not improve outcome after collagenase-induced intracerebral hemorrhage

et al. 2019

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The sulfonylurea 1 transient receptor potential melastatin 4 (Sur1-Trpm4) receptor is selectively expressed after intracerebral hemorrhage (ICH). This upregulation contributes to increases in intracellular sodium. Water follows sodium through aquaporin channels, leading to cytotoxic edema. Even after edema is thought to have resolved, ionic dyshomeostasis persists, as does blood-brain barrier (BBB) damage. Glibenclamide, a hypoglycemic agent that inhibits Sur1-Trpm4, has been shown to reduce BBB damage and edema following infusion of autologous blood into the brain (ICH) as well as after other brain injuries. In order to further assess efficacy, we used the collagenase ICH model in rats to test whether glibenclamide reduces edema, attenuates ion dyshomeostasis, improves BBB damage, and reduces lesion volume. We tested a widely-used glibenclamide dose shown effective in other studies (10 μg/kg loading dose followed by 200 ng/hr for up to 7 days). Early initiation of glibenclamide did not significantly impact edema (72 hours), BBB permeability (72 hours), or lesion volume after ICH (28 days). Recovery from neurological impairments was also not improved by glibenclamide. These results suggest that glibenclamide will not improve outcome in ICH. However, the treatment appeared to be safe as there was no effect on bleeding or other physiological variables.

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Section: Discussioncontrasting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Glibenclamide, a Sur1-Trpm4 antagonist, does not improve outcome after collagenase-induced intracerebral hemorrhage

et al. 2019

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“…Western blot was performed as described previously [36,37]. The tissues surrounding the hematoma of the right brain hemispheres of five mice from each group were harvested on day 3 after ICH or the sham operation.…”

Section: Western Blot Analysismentioning

confidence: 99%

Activation of PPAR-β/δ Attenuates Brain Injury by Suppressing Inflammation and Apoptosis in a Collagenase-Induced Intracerebral Hemorrhage Mouse Model

et al. 2020

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Brain injury has been proposed as the major cause of the poor outcomes associated with intracerebral hemorrhage (ICH). Emerging evidence indicates that the nuclear receptor, peroxisome proliferator-activated receptor β/δ (PPAR-β/δ), plays a crucial role in the pathological process of central nervous impairment. The present study was undertaken to evaluate the protective effects of PPAR-β/δ activation using a selective PPAR-β/δ agonist, GW0742, against brain injury after ICH in a mouse model. ICH was induced by intravenous injection of collagenase into the right caudate putamen. To examine the protective effect of PPAR-β/δ activation against ICH-induced brain injury, mice were either intraperitoneally injected with GW0742 (3 mg/kg, body weight) or saline (control group) 30 min before inducing ICH. Behavioral dysfunction was evaluated 24 and 72 h after injury. Then, all mice were killed to assess hematoma volume, brain water content, and blood-brain barrier (BBB) permeability. TUNEL and Nissl staining were performed to quantify the brain injury. The expression of PPAR-β/δ, interleukin (IL)-1β, tumor necrosis factor (TNF)-α, Bcl-2-related X-protein (Bax), and B-cell lymphoma 2 (Bcl-2) in the perihematomal area was examined by immunohistochemistry and western blotting analysis. Mice treated with GW0742 showed significantly less severe behavioral deficits compared to the control group, accompanied by increased expression of PPAR-β/δ and Bcl-2, and increased expression of IL-1β, TNF-α, and Bax decreased simultaneously in the GW0742-treated group. Furthermore, the GW0742-pretreated group showed significantly less brain edema and BBB leakage. Neuronal loss was attenuated, and the number of apoptotic neuronal cells in perihematomal tissues reduced, in the GW0742-pretreated group compared to the control group. However, the hematoma volume did not decrease significantly on day 3 after ICH. These results suggest that the activation of PPAR-β/δ exerts a neuroprotective effect on ICH-induced brain injury, possibly through anti-inflammatory and anti-apoptotic pathways.

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“…31 Glibenclamide is had antioxidant properties and has the hepatoprotective and neuroprotective effects that are mediated through upregulation of intracellular reactive oxygen species and inhibit of apoptosis pathway, respectively. 32,33 Diabetic animals showed increases in the levels of serum sodium levels that indicating the risk of development of renal failure. 34 The animals treated with MECZ, showed a significant reduction in serum sodium level compared with diabetic animals, which indicates that this plant has a nephroprotective effect.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant and Antidiabetic Activities of Methanolic extract of Bark of Cinnamomum zeylanicum in Diabetic Rats

Singh

Parasuraman

Kathiresan

2020

FRA

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Background: Cinnamomum zeylanicum or Ceylon cinnamon is used for the management of dyspepsia, dysmenorrhea, memory loss and tremor. It is also traditionally recommended for the management of diabetes. Further studies are required to explore the antioxidant and antidiabetic activity of various extracts of bark of C. zeylanicum. Hence, the present study is planned to investigate the antioxidant and antidiabetic activities of methanolic extract of barks of C. zeylanicum. Methods: Bark of C. zeylanicum was extracted with methanol, ethanol and acetone and its antioxidant activity was studied using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) free radical scavenging assays. Acute toxic effect of methanolic extract of C. zeylanicum (MECZ) studied as per the method described in OECD Guideline for testing of chemicals (Test Guideline 423). MECZ was studied for its antidiabetic effect using streptozotocin-induced diabetic rats. Results: In both DPPH and ABTS free radical scavenging assay, methanolic and acetone extracts exhibited free radical scavenging activity, respectively. In acute toxicity testing, MECZ did not show any significant toxic signs up to 2000 mg/kg, hence the antidiabetic activity of MECZ was carried out at the dose levels of 125, 250 and 500 mg/kg. MECZ showed antidiabetic activity from 2 nd week of the experiment onward. In the biochemical analysis, MECZ treated animals showed significant decreases in the levels of ALP and urea when compared with control. In lipid profile analysis, diabetic animals and diabetic animals treated glibenclamide showed significant increases in the levels of total cholesterol when compared with normal control and MECZ prevented the STZ-induced hyperlipidemia. At the end of the study, diabetic animals and diabetic animals treated with glibenclamide and MECZ showed significant decreases in the level of insulin when compared with the control group. In the histopathological analysis, sections from the liver, pancreas and kidney of the diabetic animals showed mid-to-moderate toxic effects and glibenclamide and MECZ 500 mg/kg prevented the STZ-induced cellular changes. Conclusion: The MECZ exhibited significant antioxidant and antidiabetic activities.

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Neuroprotective potential of glibenclamide is mediated by antioxidant and anti-apoptotic pathways in intracerebral hemorrhage

Cited by 28 publications

References 35 publications

Glibenclamide, a Sur1-Trpm4 antagonist, does not improve outcome after collagenase-induced intracerebral hemorrhage

Glibenclamide, a Sur1-Trpm4 antagonist, does not improve outcome after collagenase-induced intracerebral hemorrhage

Activation of PPAR-β/δ Attenuates Brain Injury by Suppressing Inflammation and Apoptosis in a Collagenase-Induced Intracerebral Hemorrhage Mouse Model

Antioxidant and Antidiabetic Activities of Methanolic extract of Bark of Cinnamomum zeylanicum in Diabetic Rats

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