scholarly journals Refined Qingkailing Protects MCAO Mice from Endoplasmic Reticulum Stress-Induced Apoptosis with a Broad Time Window

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Fafeng Cheng ◽  
Xianggen Zhong ◽  
Yi Lu ◽  
Xueqian Wang ◽  
Wenting Song ◽  
...  
Keyword(s):  
Brain Injury ◽  
Intracellular Calcium ◽  
Time Window ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Brain Infarction ◽  
Artery Occlusion ◽  
Neurological Function ◽  
Induced Apoptosis ◽  
Cerebral Artery Occlusion

In the current study, we are investigating effect of refined QKL on ischemia-reperfusion-induced brain injury in mice.Methods.Mice were employed to induce ischemia-reperfusion injury of brain by middle cerebral artery occlusion (MCAO). RQKL solution was administered with different doses (0, 1.5, 3, and 6 mL/kg body weight) at the same time of onset of ischemia, and with the dose of 1.5 mL/kg at different time points (0, 1.5, 3, 6, and 9 h after MCAO). Neurological function and brain infarction were examined and cell apoptosis and ROS at prefrontal cortex were evaluated 24 h after MCAO, and western blot and intracellular calcium were also researched, respectively.Results.RQKL of all doses can improve neurological function and decrease brain infarction, and it performed significant effect in 0, 1.5, 3, and 6 h groups. Moreover, RQKL was able to reduce apoptotic process by reduction of caspase-3 expression, or restraint of eIF2a phosphorylation and caspase-12 activation. It was also able to reduce ROS and modulate intracellular calcium in the brain.Conclusion.RQKL can prevent ischemic-induced brain injury with a time window of 6 h, and its mechanism might be related to suppress ER stress-mediated apoptotic signaling.

scholarly journals Baicalin’s Therapeutic Time Window of Neuroprotection during Transient Focal Cerebral Ischemia and Its Antioxidative EffectsIn VitroandIn Vivo

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Fafeng Cheng ◽  
Yi Lu ◽  
Xianggen Zhong ◽  
Wenting Song ◽  
Xueqian Wang ◽  
...  
Keyword(s):  
Time Window ◽  
Ischemia Reperfusion Injury ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Brain Infarction ◽  
Artery Occlusion ◽  
Sod Activity ◽  
Neuroprotective Effects

We investigated the effects of baicalin on an ischemia-reperfusion-induced brain injury model in rats and its antioxidative activitiesin vitroandin vivo. An ischemia-reperfusion injury of the brain via a middle cerebral artery occlusion (MCAO) was induced in rats. Baicalin was injected at different time points (0, 2, 4, and 6 h) after the MCAO was induced. Baicalin can improve neurological function and significantly decrease brain infarction within a time window of 4 h. Moreover, baicalin was able to reduce cell apoptosis and had the strong antioxidative effect of reducing reactive oxygen species production and malondialdehyde generation. In contrast, baicalin interfered with superoxide dismutase and nicotinamide adenine dinucleotide 2′-phosphate oxidase activities. Moreover, baicalin also exhibited strong neuroprotective effects against H2O2-mediated injury and improved the SOD activity of neurons. Furthermore, baicalin demonstrated good scavenging of hydroxyl radicals, superoxide anions, and DPPH radicals and exerted an additional effect of inhibiting xanthine oxidase. Baicalin showed beneficial effects against MCAO-induced injury within a 4 h time window, and its antioxidative effects bothin vitroandin vivomay partly elucidate its mechanism of action.

MitoKATP opener, diazoxide, reduces neuronal damage after middle cerebral artery occlusion in the rat

2002 ◽  
Vol 283 (3) ◽  
pp. H1005-H1011 ◽  
Author(s):  
Katsuyoshi Shimizu ◽  
Zsombor Lacza ◽  
Nishadi Rajapakse ◽  
Takashi Horiguchi ◽  
James Snipes ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Ischemia Reperfusion Injury ◽  
Neuronal Damage ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Sham Treatment ◽  
Cerebral Artery Occlusion

We investigated effects of diazoxide, a selective opener of mitochondrial ATP-sensitive K+ (mitoKATP) channels, against brain damage after middle cerebral artery occlusion (MCAO) in male Wistar rats. Diazoxide (0.4 or 2 mM in 30 μl saline) or saline (sham) was infused into the right lateral ventricle 15 min before MCAO. Neurological score was improved 24 h later in the animals treated with 2 mM diazoxide (13.8 ± 0.7, n = 13) compared with sham treatment (9.5 ± 0.2, n = 6, P < 0.01). The total percent infarct volume (MCAO vs. contralateral side) of sham treatment animals was 43.6 ± 3.6% ( n = 12). Treatment with 2 mM diazoxide reduced the infarct volume to 20.9 ± 4.8% ( n = 13, P < 0.05). Effects of diazoxide were prominent in the cerebral cortex. The protective effect of diazoxide was completely prevented by the pretreatment with 5-hydroxydecanoate (100 mM in 10 μl saline), a selective blocker of mitoKATP channels ( n = 6). These results indicate that selective opening of the mitoKATP channel has neuroprotective effects against ischemia-reperfusion injury in the rat brain.

scholarly journals Endothelial Conditional Knockdown of NMMHC IIA (Nonmuscle Myosin Heavy Chain IIA) Attenuates Blood-Brain Barrier Damage During Ischemia-Reperfusion Injury

Stroke ◽  
2021 ◽  
Vol 52 (3) ◽  
pp. 1053-1064
Author(s):  
Shuaishuai Gong ◽  
Guosheng Cao ◽  
Fang Li ◽  
Zhuo Chen ◽  
Xuewei Pan ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Endothelial Barrier ◽  
Nonmuscle Myosin ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Artery Occlusion

Background and Purpose: In ischemic stroke, breakdown of the blood-brain barrier (BBB) aggravates brain damage. Endothelial detachment contributes to BBB disruption and neurovascular dysfunction, but its regulation in stroke has yet to be clarified. We investigated the function of NMMHC IIA (nonmuscle myosin heavy chain IIA) in the endothelium on BBB breakdown and its potential mechanisms. Methods: Endothelial conditional knockdown NMMHC IIA ( Myh9 ECKD ) was constructed in vivo and in vitro, and its role was explored in middle cerebral artery occlusion/reperfusion–injured mice and oxygen-glucose deprivation/reoxygenation–injured brain microvascular endothelial cells. The degree of brain injury was analyzed using staining (2,3,5-triphenyltetrazolium chloride, hematoxylin, and eosin) and electron microscopy. BBB breakdown was investigated with leakage of Evans Blue dye and expression of TJs (tight junctions) and MMP (matrix metallopeptidase)-2/9. Transcriptomics for enrichment analysis was adopted to explore the potential downstream signaling pathways of NMMHC IIA involved in middle cerebral artery occlusion/reperfusion–induced BBB dysfunction. Results: NMMHC IIA expression was upregulated in endothelial cells after cerebral ischemia/reperfusion injury. Myh9 ECKD mice exhibited improvement in endothelial barrier hyperpermeability and TJs integrity stimulated by cerebral ischemia/reperfusion. Blebbistatin (NMMHC II inhibitor) treatment exerted the same effect. Transcriptomics showed that NMMHC IIA was involved in regulating various BBB-related genomic changes in the middle cerebral artery occlusion/reperfusion model, and NMMHC IIA was confirmed to significantly modulate Hippo and peroxisome proliferator-activated receptor gamma/nuclear factor-kappa B signaling pathways, which are closely related to BBB damage. Conclusions: Our findings provide some new insights into how NMMHC IIA contributes to maintaining the integrity of the cerebral endothelial barrier. NMMHC IIA could be a potential therapeutic target for ischemic stroke.

scholarly journals Calycosin-7-O-β-D-Glucoside Treatment Promotes Axonal Regeneration via Rho/ROCK Pathway After Ischemia/Reperfusion Injury

2020 ◽  
Author(s):  
Nijun Zhong ◽  
Aiming Yu ◽  
Guiqing Wen ◽  
Lanying Zhong ◽  
Yingying He ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Axonal Regeneration ◽  
Cell Damage ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Neurological Function ◽  
Triphenyltetrazolium Chloride ◽  
Nissl Staining ◽  
Cerebral Artery Occlusion ◽  
Medical Component

Abstract Background: As a medical component in Astragalus(AR) ，Calycosin-7- O -β-D-glucoside（CG）defends ischemia/reperfusion(I/R) injury in cerebral ischemia due to its anti-oxidative and anti-inflammatory effects. However, whether CG can facilitate I/R injury by stimulating neuroregeneration and its specific mechanism is remained to be elucidated. Methods: In this study, an animal model of ischemic stroke was established by middle cerebral artery occlusion (MCAO). Seven days after CG, triphenyltetrazolium chloride (TTC) staining was performed to examine the ischemic volume, accompanied by behavioral tests to assess neurological function. Nissl staining and Bielschowsky’s silver staining were used to observe nerve cell damage and axonal loss, while immunofluorescence was used to evaluate axonal regeneration. Results: The expression of proteins associated with the Rho/ROCK pathway was detected by using western blot (WB) and quantitative real-time polymerase chain reaction (qRT-PCR). We showed that CG significantly reduced ischemic volume, facilitated axonal regeneration, improved neurological function, and regulated expression of RGMa, Rho, ROCK, and CRMP2. Conclusions: Our results suggested that CG promotes axonal regeneration by limiting activation of the Rho/ROCK pathway to promote recovery after cerebral ischemia.

scholarly journals Stargazin Interaction With Serine Racemase Mediates Cerebral Ischemia/Reperfusion Injury in Rats

2021 ◽  
Author(s):  
Xiaqing Yuan ◽  
Shanshan Diao ◽  
Shujun Chen ◽  
Jiajie Lu ◽  
Haitao Shen ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Serine Racemase ◽  
Dependent Protein ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Cerebral Ischemic ◽  
Cerebral Ischemic Damage ◽  
Cerebral Artery Occlusion

Abstract D-Serine is thought to be involved in N-methyl-D-aspartate (NMDA)-type glutamate receptor-mediated neurotoxicity and plays a pathophysiologic role in stroke. D-Serine is synthesized by serine racemase (SR), which directly converts L-serine into D-serine. The deletion of SR has been reported to protect against cerebral ischemia damage. Additionally, SR catalytic activity is physiologically regulated by its binding to stargazin. However, whether the stargazin-SR interaction affects the level of stroke damage remains elusive. We showed that cerebral ischemia increased the interaction of stargazin and SR and decreased the levels of D-serine. Disrupting the stargazin-SR interaction by knocking down stargazin aggravated cerebral ischemic insults. We found that cerebral ischemia decreased the phosphorylation of stargazin at the Thr-321 residue, which was phosphorylated by cAMP-dependent protein kinase A (PKA). Treatment with the PKA inhibitor H89 blocked stargazin T321 phosphorylation, augmented the stargazin-SR interaction, decreased D-serine levels, and alleviated focal cerebral ischemic damage in rats subjected to middle cerebral artery occlusion and reperfusion (MCAO/R). Thus, the stargazin-SR interaction is a promising strategy in the treatment of stroke.

scholarly journals Neuroprotective effect ofPanax ginsengextract against cerebral ischemia–reperfusion-injury-induced oxidative stress in middle cerebral artery occlusion models

FACETS ◽  
2019 ◽  
Vol 4 (1) ◽  
pp. 52-68 ◽  
Author(s):  
Mufzala Shamim ◽  
Nazish Iqbal Khan
Keyword(s):  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Lipid Profile ◽  
Liver Enzymes ◽  
Ischemia Reperfusion Injury ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Liver And Kidney ◽  
Cerebral Artery Occlusion

The present study investigated the in vivo neuroprotective role of Panax ginseng extract (PGE) pretreatment against transient cerebral ischemia in a middle cerebral artery occlusion (MCAO) model. Rats were randomly divided as follows: group I, control; group II, sham-operated; group III, where animals were subjected to MCAO surgery; and group IV, where animals were orally administered 10 mL PGE per day (200 mg/kg of body weight per day) for 30 d followed by MCAO induction at day 31. Following 24 h of reperfusion, blood and tissue (brain, liver, and kidney) samples were collected for biochemical and histopathological examination. Biochemical testing included lipid profile, liver enzymes, kidney function tests, C-reactive protein (CRP), lactate dehydrogenase (LDH), glucose, and total protein estimation. Tissue antioxidants (catalase, superoxide dismutase, and glutathione) were assessed in brain, liver, and kidney tissues. MCAO-induced histopathological changes were also examined in the tissues. Pretreatment with PGE showed significant improvement in tissue antioxidant status in brain, liver and kidney tissues. PGE treatment maintains plasma lipid profile, liver enzymes, kidney function, and CRP, LDH, and glucose levels. Histologically, monocytes and macrophage infiltration were observed in the tissues of MCAO animals, whereas PGE treatment preserved tissue architecture and minimal monocyte infiltration. PGE supplementation showed a neuroprotective effect against ischemia–reperfusion injury by effectively increasing endogenous antioxidant enzyme activity.

scholarly journals Adiponectin-Transfected Endothelial Progenitor Cells Have Protective Effects After 2-Hour Middle-Cerebral Artery Occlusion in Rats With Type 2 Diabetes Mellitus

2021 ◽  
Vol 12 ◽  
Author(s):  
Meiyao Wang ◽  
Yan Li ◽  
Renwei Zhang ◽  
Shuaimei Zhang ◽  
Hongliang Feng ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Artery Occlusion ◽  
Protective Effects ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Cerebral Artery Occlusion

Objectives: This present study aimed to examine the effects of adiponectin-transfected endothelial progenitor cells (LV-APN-EPCs) on cerebral ischemia–reperfusion injury in rats with type 2 diabetes mellitus (T2DM) and to explore the underlying mechanisms.Methods: Seventy male Sprague–Dawley rats with T2DM were randomly divided into sham, phosphate-buffered saline (PBS), LV-APN-EPCs, LV-EPCs, and EPCs groups. Transient middle cerebral artery occlusion (MCAO) was induced by the intraluminal suture method. After 1 h of reperfusion, the five interventions were performed by tail-vein injections. The modified neurological severity score (mNSS) was used to assess neurological function before and on days 1, 7, and 14 after MCAO. After 14 days, magnetic resonance imaging scanning, hematoxylin and eosin staining, terminal dUTP nick-end labeling staining, Western blotting analysis, cluster of differentiation (CD) 31 immunofluorescence, and enzyme-linked immunosorbent assay were used to evaluate infarct rate, morphological damage, cell apoptosis, and microvessel density.Results: Compared with PBS, LV-EPCs, and EPCs groups, the LV-APN-EPCs group showed significantly lower mNSS score, lower infarct rate, and less morphological damage (all P &lt; 0.05). In addition, compared with other groups, the LV-APN-EPCs group had significantly increased levels of B cell lymphoma/leukemia-2 (Bcl-2) protein, CD31+ microvessels, endothelial nitric oxide synthase, and vascular endothelial growth factor, and decreased levels of Bcl-2-associated X protein and neuronal apoptosis in the peri-infarct cortex (all P &lt; 0.05).Conclusion: These results suggest that LV-APN-EPCs exert protective effects against cerebral ischemia–reperfusion injury in T2DM rats by increasing angiogenesis.

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