Glibenclamide ameliorates ischemia–reperfusion injury via modulating oxidative stress and inflammatory mediators in the rat hippocampus

Abdallah, Dalaal M.; Nassar, Noha N.; Abdelsalam, Rania M.

doi:10.1016/j.brainres.2011.02.007

Cited by 60 publications

(55 citation statements)

References 38 publications

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“…1,7 However, glibenclamide administration resulted in ameliorated reperfusion-derived oxidative stress and proinflammatory cytokine release in the rat hippocampus after cerebral ischemia in rats. 9 In line with this, our previous study demonstrated that glibenclamide administration at 6, 12, and 24 hours after reperfusion caused early neuroprotection and this was accompanied by a better neurological outcome. 8 Although recently Simard et al 10 showed an extended time window for glibenclamide treatment from 6 to 10 hours after onset of cerebral ischemia, and several studies point to a beneficial effect of glibenclamide to treat stroke, no previous studies have evaluated the long-term effects of glibenclamide administration on brain repair and its correlation with functional outcomes after stroke.…”

Section: Introductionsupporting

confidence: 67%

“…36 Furthermore, angiogenesis is considered a key feature of ischemic stroke recovery and neuronal post-stroke re-organization. 37 Several studies using experimental stroke models have indicated the beneficial effects of glibenclamide administration after reperfusion, such as reversing ischemia-reperfusion injury by halting oxidative stress and inflammation in the hippocampus, 9 preventing cytotoxic edema after cerebral ischemia, 2,3,1,7 and enhancing neuroprotection, which all eventually lead to a better functional outcome. 8 Thus, although glibenclamide did not modify the size and cell density of microglia nor astroglia after ischemia here, it enhanced long-term brain repair processes and functional recovery outcomes of the rats.…”

Section: Discussionmentioning

confidence: 99%

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Glibenclamide Enhances Neurogenesis and Improves Long-Term Functional Recovery after Transient Focal Cerebral Ischemia

Ortega

Jolkkonen

Mahy

et al. 2012

J Cereb Blood Flow Metab

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Glibenclamide is neuroprotective against cerebral ischemia in rats. We studied whether glibenclamide enhances long-term brain repair and improves behavioral recovery after stroke. Adult male Wistar rats were subjected to transient middle cerebral artery occlusion (MCAO) for 90 minutes. A low dose of glibenclamide (total 0.6 mg) was administered intravenously 6, 12, and 24 hours after reperfusion. We assessed behavioral outcome during a 30-day follow-up and animals were perfused for histological evaluation. In vitro specific binding of glibenclamide to microglia increased after pro-inflammatory stimuli. In vivo glibenclamide was associated with increased migration of doublecortin-positive cells in the striatum toward the ischemic lesion 72 hours after MCAO, and reactive microglia expressed sulfonylurea receptor 1 (SUR1) and Kir6.2 in the medial striatum. One month after MCAO, glibenclamide was also associated with increased number of NeuN-positive and 5-bromo-2-deoxyuridine-positive neurons in the cortex and hippocampus, and enhanced angiogenesis in the hippocampus. Consequently, glibenclamide-treated MCAO rats showed improved performance in the limb-placing test on postoperative days 22 to 29, and in the cylinder and water-maze test on postoperative day 29. Therefore, acute blockade of SUR1 by glibenclamide enhanced long-term brain repair in MCAO rats, which was associated with improved behavioral outcome.

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Section: Introductionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Glibenclamide Enhances Neurogenesis and Improves Long-Term Functional Recovery after Transient Focal Cerebral Ischemia

Ortega

Jolkkonen

Mahy

et al. 2012

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…In addition, previous studies suggest that glibenclamide possesses anti-oxidant profiles (10,21). It has been reported that glibenclamide may improve neurological outcome in animal models of stroke (21,22). During sepsis, it is often associated with exacerbated production of free radicals (12), which was also observed in the present study.…”

supporting

confidence: 74%

“…Together, these data suggested the antiinflammatory profile of glibenclamide is partially dependent on NLRP3 activation. In addition, previous studies suggest that glibenclamide possesses anti-oxidant profiles (10,21). It has been reported that glibenclamide may improve neurological outcome in animal models of stroke (21,22).…”

mentioning

confidence: 99%

Glibenclamide Pretreatment Attenuates Acute Lung Injury by Inhibiting the Inflammatory Responses and Oxidative Stress in a Polymicrobial Sepsis Animal Model

Ji¹,

Yang²,

Ju³

et al. 2014

J Anesth Perioper Med

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“…However, there are other reports describing beneficial effects of SU drugs in rodent models of cerebral ischemia (6)(7)(8). Interestingly, in the brain, SUR1 serves as a regulatory subunit for both the K ATP channel and a nonselective cation channel, NC Ca-ATP (9).…”

mentioning

confidence: 99%

Is There Enhanced Risk of Cerebral Ischemic Stroke by Sulfonylureas in Type 2 Diabetes?

Parkinson

Hatch

2016

Diabetes

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Hyperglycemia enhances stroke injury in humans and experimental animals, and type 2 diabetes mellitus (T2DM) is a known risk factor for stroke. Sulfonylurea (SU) drugs have been used for over six decades for management of T2DM; they exhibit their principal antidiabetes property by inhibiting K ATP channels and promoting an increase in insulin secretion by pancreatic b-cells (1,2) (Fig. 1A). The K ATP channel in the pancreas is a complex of four subunits of the KCNJ11 gene product Kir6.2 and four subunits of the ABCC8 gene product SUR1 (3). SU drugs bind to SUR1 to block the K ATP channel.Although treatment of T2DM reduces stroke risk, the study by Liu et al. (4) in this issue of Diabetes addresses the question of whether SU drugs can enhance stroke risk and stroke injury by inhibiting K ATP channels in brain. The study makes three points. First, a 5-day administration of streptozotocin (STZ) to mice led to persistent hyperglycemia (blood glucose .16 mmol/L) and decreased body weight (,10% from controls); following a 90-min transient middle cerebral artery occlusion (MCAO), infarct size and neurological deficit were both significantly greater in mice given STZ. Second, in cortical mouse neurons subjected to oxygen-glucose deprivation and in normoglycemic mice subjected to permanent MCAO, neuronal cell death and stroke injury were increased with the SU tolbutamide but decreased with the K ATP channel opener diazoxide. Third, a meta-analysis of human clinical trials in patients with T2DM was performed. Seventeen randomized controlled trials, with a combined total of over 27,000 patients, that compared SUs to placebo or other antidiabetes drugs and reported stroke incidence were included. The analysis revealed a .30% increase in the incidence of stroke in patients treated with SUs. Thus, this report concludes that SU drugs increase stroke risk and are used in a patient population that is already at greater risk of stroke (4).The study by Liu et al. supports the findings of a previous study by the senior authors, which reported increased stroke injury using transient MCAO in Kir6.2 knockout mice relative to wild-type mice (5). However, there are other reports describing beneficial effects of SU drugs in rodent models of cerebral ischemia (6-8). Interestingly, in the brain, SUR1 serves as a regulatory subunit for both the K ATP channel and a nonselective cation channel, NC Ca-ATP (9). The pore-forming subunit of the NC Ca-ATP channel was recently identified as Trpm4 (10). The NC Ca-ATP channel conducts monovalent cations, is activated by depletion of cellular ATP, and requires nanomolar concentrations of Ca 2+ for opening (11). Thus, ischemic conditions are reported to trigger opening of both K ATP and NC Ca-ATP channels, but whereas K ATP channel opening is hyperpolarizing, NC Ca-ATP channel opening is depolarizing (Fig. 1B). In rodent models of cerebral stroke, it was demonstrated that blockage of newly expressed SUR1 in ischemic neurons, astrocytes, and capillaries with a low dose of the SU glibenclamide reduced c...

show abstract

Glibenclamide ameliorates ischemia–reperfusion injury via modulating oxidative stress and inflammatory mediators in the rat hippocampus

Cited by 60 publications

References 38 publications

Glibenclamide Enhances Neurogenesis and Improves Long-Term Functional Recovery after Transient Focal Cerebral Ischemia

Glibenclamide Enhances Neurogenesis and Improves Long-Term Functional Recovery after Transient Focal Cerebral Ischemia

Glibenclamide Pretreatment Attenuates Acute Lung Injury by Inhibiting the Inflammatory Responses and Oxidative Stress in a Polymicrobial Sepsis Animal Model

Is There Enhanced Risk of Cerebral Ischemic Stroke by Sulfonylureas in Type 2 Diabetes?

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