scholarly journals A possible molecular mechanism of hearing loss during cerebral ischemia in mice

2015 ◽  
Vol 93 (7) ◽  
pp. 505-516 ◽  
Author(s):  
Pradip Kumar Kamat ◽  
Anuradha Kalani ◽  
Naira Metreveli ◽  
Suresh C. Tyagi ◽  
Neetu Tyagi
Keyword(s):  
Hearing Loss ◽  
Cerebral Ischemia ◽  
Connexin 43 ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Fluorescein Isothiocyanate ◽  
Blue Staining ◽  
Lesion Volume ◽  
Triphenyltetrazolium Chloride ◽  
Auditory Response

Ischemic brain stroke is a leading cause of disability and includes hearing loss. Clinical reports have also suggested that there is hearing loss in stroke patients but the mechanism was not determined. Therefore, we hypothesized that hearing loss after cerebral ischemia may be associated with changes to the synapse, gap junction, and sodium channel (NaC) proteins. Ischemia–reperfusion injury was induced in wild-type mice (I/R group). The lesion volume was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining of the brain sections. BBB disruption was confirmed by Evans blue staining and leakage of bovine serum albumin labeled with fluorescein isothiocyanate (BSA-FITC). We found that brain edema, infarct size, and permeability were increased in ischemic mice as compared with the sham-operated group. Caspase-3, caspase-9, and TUNEL-positive cells were increased in I/R mice, indicating neuronal apoptosis. Moreover, there were increased expressions of matrix metalloprotease’s (MMP-2, -3, -9, and -13), interleukin (IL)-6, and decreased expressions of tight junction proteins (TJP) in the I/R group, as compared with the sham group, which signifies inflammation and BBB disruption. We also observed decreased levels of post-synaptic density protein-95 (PSD-95), synapse-associated protein 97 (SAP-97), connexin-43, NaC-α, and NaC-β, and increased expression of connexin-45, whereas no substantial change was observed in connexin-26 expression in the I/R group. Interestingly, auditory response was reduced in the I/R mice, indicating hearing loss. These data suggest that hearing loss in ischemic mice was primarily due to alterations in connexin, synapses, and NaC channels.

scholarly journals The neuroprotective effect of pretreatment with carbon dots from Crinis Carbonisatus (carbonized human hair) against cerebral ischemia reperfusion injury

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yue Zhang ◽  
Suna Wang ◽  
Fang Lu ◽  
Meiling Zhang ◽  
Hui Kong ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Carbon Dots ◽  
Ischemia Reperfusion Injury ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Inflammatory Factors ◽  
Lesion Volume ◽  
Ischemic Lesion ◽  
Tnf Α

Abstract Background Cerebral infarction and cerebral hemorrhage, also known as “stroke”, is one of the leading cause of death. At present, there is no real specific medicine for stroke. Crinis Carbonisatus (named Xue-yu-tan in Chinese), produced from carbonized hair of healthy human, and has been widely applied to relieve pain and treat epilepsy, stroke and other diseases in China for thousands of years. Results In this work, a new species of carbon dots derived from Crinis Carbonisatus (CrCi-CDs) were separated and identified. And the neuroprotective effect of carbon dots from CrCi were evaluated using the middle cerebral artery occlusion (MCAO) model. Neurological deficit score and infarction volume was assessed, evans blue content of ischemic hemispheres was measured, the concentrations of inflammatory factors, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) in the cortex were measured, and the levels of neurotransmitters in the brain were determined. Preconditioning of CrCi-CDs significantly reduced ischemic lesion volume and blood–brain-barrier (BBB) permeability, improved neurologic deficits, decreased the level of TNF-α and IL-6 in MCAO rats, inhibited excitatory neurotransmitters aspartate (Asp) and glutamate (Glu), and increased the level of 5-hydroxytryptamine (5-HT). The RNA-Sequencing results reveal that further potential mechanisms behind the activities may be related to the anti-inflammation effects and inhibition of neuroexcitatory toxicity. Conclusion CrCi-CDs performs neuroprotective effect on cerebral ischemia and reperfusion injury, and the mechanisms may correlate with its anti-inflammatory action, which suggested that CrCi-CDs have potential value in clinical therapy on the acute apoplexy cases in combination with thrombolytic drugs. Graphic abstract

scholarly journals Guhong Injection Alleviates Cerebral Ischemia–Reperfusion Injury via the PKC/HIF-1α Pathway in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Li Yu ◽  
Yangyang Zhang ◽  
Xixi Zhao ◽  
Haitong Wan ◽  
Yu He ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Hypoxia Inducible Factor ◽  
Positive Control ◽  
Artery Occlusion ◽  
Enzyme Linked Immunosorbent Assay ◽  
Sprague Dawley ◽  
Triphenyltetrazolium Chloride ◽  
Cerebral Ischemia Reperfusion

Guhong injection (GHI) is a drug for ischemic stroke created by combining safflower, a traditional Chinese medicine, and aceglutamide, a Western medicine. In this study, we investigated the curative effect of GHI on cerebral ischemia–reperfusion (I/R) injury via the PKC/HIF-1α pathway in rats. Adult male Sprague Dawley rats were randomly divided into seven groups: sham-operated, middle cerebral artery occlusion (MCAO), GHI, nimodipine injection (NMDP), MCAO + LY317615 (PKC inhibitor), GHI + LY317615, and NMDP + LY317615. After establishing an MCAO rat model, we performed neurological deficit testing, 2,3,5-triphenyltetrazolium chloride staining, hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assay, Western blotting, and q-PCR to detect the brain damage in rats. Compared with the MCAO group, the GHI and GHI + LY317615 group showed neurological damage amelioration as well as decreases in serum hypoxia-inducible factor-1α (HIF-1α), protein kinase C (PKC), and erythropoietin levels; brain HIF-1α and inducible nitric oxide synthase protein expression; and brain HIF-1α and NOX-4 mRNA expression. These effects were similar to those in the positive control groups NMDP and NMDP + LY317615. Thus, our results confirmed GHI can ameliorate cerebral I/R injury in MCAO rats possibly via the PKC/HIF-1α pathway.

scholarly journals Neuroprotection in Ischemia–Reperfusion Injury: An Antiinflammatory Approach Using a Novel Broad-Spectrum Chemokine Inhibitor

2001 ◽  
Vol 21 (6) ◽  
pp. 683-689 ◽  
Author(s):  
John S. Beech ◽  
Jill Reckless ◽  
David E. Mosedale ◽  
David J. Grainger ◽  
Steve C. R. Williams ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Inflammatory Response ◽  
Reperfusion Injury ◽  
Inflammatory Cell ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Lesion Volume ◽  
Cerebral Ischemia Reperfusion ◽  
Tnf Α ◽  
Cerebral Ischemia Reperfusion Injury

Cerebral ischemia–reperfusion injury is associated with a developing inflammatory response with pathologic contributions from vascular leukocytes and endogenous microglia. Signaling chemokines orchestrate the communication between the different inflammatory cell types and the damaged tissue leading to cellular chemotaxis and lesion occupation. Several therapies aimed at preventing this inflammatory response have demonstrated neuroprotective efficacy in experimental models of stroke, but to date, few investigators have used the chemokines as potential therapeutic targets. In the current study, the authors investigate the neuroprotective action of NR58–3.14.3, a novel broad-spectrum inhibitor of chemokine function (both CXC and CC types), in a rat model of cerebral ischemia–reperfusion injury. Rats were subjected to 90 minutes of focal ischemia by the filament method followed by 72 hours of reperfusion. Both the lesion volume, measured by serial magnetic resonance imaging, and the neurologic function were assessed daily. Intravenous NR58–3.14.3 was administered, 2 mg/kg bolus followed by 0.5 mg/kg · hour constant infusion for the entire 72-hour period. At 72 hours, the cerebral leukocytic infiltrate, tumor necrosis factor-α (TNF-α), and interleukin-8 (IL-8)-like cytokines were analyzed by quantitative immunofluorescence. NR58–3.14.3 significantly reduced the lesion volume by up to 50% at 24, 48, and 72 hours post–middle cerebral artery occlusion, which was associated with a marked functional improvement to 48 hours. In NR58–3.14.3-treated rats, the number of infiltrating granulocytes and macrophages within perilesional regions were reduced, but there were no detectable differences in inflammatory cell numbers within core ischemic areas. The authors reported increased expression of the cytokines, TNF-α, and IL-8–like cytokines within the ischemic lesion, but no differences between the NR58–3.14.3-treated rats and controls were reported. Although chemokines can have pro-or antiinflammatory action, these data suggest the overall effect of chemokine up-regulation and expression in ischemia–reperfusion injury is detrimental to outcome.

scholarly journals Microglia-derived FGF21 as a modulator of astrocytic phenotype and cerebral ischemia injury

2020 ◽  
Author(s):  
Fei Liu ◽  
Dongxue Wang ◽  
Liyun Zhu ◽  
Jingting Du ◽  
Ping Lin ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Cell Counting ◽  
Fibroblast Growth Factor 21 ◽  
Protective Effects ◽  
Triphenyltetrazolium Chloride

Abstract Background: Fibroblast growth factor 21 (FGF21) is an important neuroprotective factor in the central nervous system (CNS), and it has been reported that FGF21 can protect against cerebral ischemia during the acute phase. However, the possible effects of FGF21 on ischemic brains and the interactions between FGF21 and nonneuronal cells have not been examined. Thus, the aim of this study was to elucidate the protective effects of endogenous FGF21 in ischemic brains.Methods: In this study, in vivo ischemia/reperfusion injury mouse model established by transient middle cerebral artery occlusion (MCAO)/reperfusion and in vitro cell models of oxygen/glucose deprivation (OGD)/reoxygenation (R) were used. Western blot analysis, RT-PCR, double immunofluorescence staining, immunohistochemistry, 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (H&E) staining, neurobehavioral tests, cell counting kit-8 (CCK-8) assay and high-throughput gene sequencing were employed to explore the mechanism by which FGF21 unleash neuroprotective effort of astrocyte phenotype shifts in ischemic stroke.Results: We found that cortical FGF21 expression significantly increased after MCAO/reperfusion, peaking at 7 d. Ischemia-activated microglia were the main sources of endogenous FGF21 in brain tissue. However, FGF21 deficiency aggravated brain injury and slowed neurological functional recovery in FGF21 knockout mice. The in vitro and vivo studies revealed that FGF21 could activate astrocytes and mediate astrocytic phenotype. FGF21-activated astrocytes contributed to neuronal survival and synaptic protein upregulation after ischemia.Conclusion: Collectively, our data indicate that FGF21 plays vital roles in alleviating ischemic brain by mediating the manifestation of potentially pro-recovery astrocytic phenotypes. Therefore, modulation of FGF21 is a potential target strategy for stroke.

scholarly journals Scavenger Receptor Class-A Has a Central Role in Cerebral Ischemia–Reperfusion Injury

2010 ◽  
Vol 30 (12) ◽  
pp. 1972-1981 ◽  
Author(s):  
Chen Lu ◽  
Fang Hua ◽  
Li Liu ◽  
Tuanzhu Ha ◽  
John Kalbfleisch ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Infarct Size ◽  
Intracellular Signaling ◽  
Ischemia Reperfusion Injury ◽  
Neuronal Damage ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Scavenger Receptor ◽  
Triphenyltetrazolium Chloride ◽  
Cerebral Ischemia Reperfusion

The innate immune response is involved in the pathophysiology of cerebral ischemia–reperfusion (I/R) injury. Recent evidence suggests that scavenger receptors have a role in the induction of innate immunity. In this study, we examined the role of scavenger receptor A (SR-A) in focal cerebral I/R injury. Both SR-A−/− mice ( n=10) and age-matched wild-type (WT) mice ( n=9) were subjected to focal cerebral ischemia (60 minutes), followed by reperfusion (for 24 hours). Infarct size was determined by TTC (triphenyltetrazolium chloride) staining. The morphology of neurons in the brain sections was examined by Nissl's staining. Activation of intracellular signaling was analyzed by western blot. Cerebral infarct size in SR-A−/− mice was significantly reduced by 63.9% compared with WT mice after cerebral I/R. In SR-A−/− mice, there was less neuronal damage in the hippocampus compared with WT mice. Levels of FasL, Fas, FADD, caspase-3 activity, and terminal deoynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate-biotin nick end labeling-positive apoptotic cells were significantly increased in WT mice after cerebral I/R, but not in SR-A−/− mice. Cerebral I/R increased nuclear factor-κB activation in WT mice, but not in SR-A−/− mice. These data suggest that SR-A has a central role in cerebral I/R injury and that suppression of SR-A may be a useful approach for ameliorating brain injury in stroke patients.

scholarly journals DJ-1 Protects against Neurodegeneration Caused by Focal Cerebral Ischemia and Reperfusion in Rats

2007 ◽  
Vol 28 (3) ◽  
pp. 563-578 ◽  
Author(s):  
Daijiro Yanagisawa ◽  
Yoshihisa Kitamura ◽  
Masatoshi Inden ◽  
Kazuyuki Takata ◽  
Takashi Taniguchi ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Focal Cerebral Ischemia ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Neuronal Cell ◽  
Ischemia And Reperfusion ◽  
Triphenyltetrazolium Chloride ◽  
Cerebral Ischemia And Reperfusion

Reactive oxygen species (ROS) is massively produced in the brain after cerebral ischemia and reperfusion. It reacts strongly with cellular components, which has detrimental effects and leads to neuronal cell death. DJ-1, which was found to be the causative gene of familial Parkinson's disease PARK7, is a multifunction protein, which plays a key role in transcriptional regulation, and a molecular chaperone. In this study, we investigated the neuroprotective effect of DJ-1 against neurodegeneration caused by ischemia/reperfusion injury. Cerebral ischemia was induced in rats by 120 mins of middle cerebral artery occlusion (MCAO) using an intraluminal introduction method. The intrastriatal injection of recombinant glutathione S-transferase-tagged human DJ-1 (GST-DJ-1) markedly reduced infarct size in 2,3,5-triphenyltetrazolium chloride staining at 3 days after MCAO. In addition, we performed a noninvasive evaluation of ischemic size using magnetic resonance imaging and found a significant reduction of infarct size with the administration of GST-DJ-1. In GST-DJ-1-treated rats, behavioral dysfunction and nitrotyrosine formation were significantly inhibited. Furthermore, GST-DJ-1 markedly inhibited H2O2-mediated ROS production in SH-SY5Y cells. These results indicate that GST-DJ-1 exerts a neuroprotective effect by reducing ROS-mediated neuronal injury, suggesting that DJ-1 may be a useful therapeutic target for ischemic neurodegeneration.

scholarly journals Rapamycin Pretreatment Alleviates Cerebral Ischemia/Reperfusion Injury in Dose-Response Manner Through Inhibition of the Autophagy and NFκB Pathways in Rats

Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582094619
Author(s):  
Liru Li ◽  
Jie Huang
Keyword(s):  
Cerebral Ischemia ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Vehicle Group ◽  
Sprague Dawley ◽  
Triphenyltetrazolium Chloride ◽  
Cerebral Ischemia Reperfusion ◽  
Y Maze

Although rapamycin can attenuate cerebral ischemia/reperfusion (I/R) injury, the potential roles of rapamycin on cerebral I/R injury remain largely controversial. The present work aims to evaluate underlying molecular mechanisms of rapamycin pretreatment on I/R injury. In total, 34 Sprague-Dawley rats were randomly grouped to 3 groups: sham group (n = 2), vehicle group (n = 16), and rapamycin-pretreatment group (n = 16). Before the focal cerebral ischemia was induced, those rats in the pretreatment group were intraperitoneally injected rapamycin (1 mg/kg body) for 20 hours, while rats in the vehicle group received same-volume saline. Then, rats in these 2 groups received focal cerebral ischemia for 3 and 6 hours, respectively (n = 8 in each group), which was followed by the application of reperfusion for 4, 24, 72 hours, and 1 week (n = 2 in each group). The results showed that the rapamycin pretreatment improved the memory functions of rats after I/R injury, which was evaluated using a Y-maze test. Rapamycin pretreatment significantly reduced the size of triphenyltetrazolium chloride infarction and decreased the expression of I/R injury markers. Moreover, the expression of LC-3 and NFκB was also significantly reduced after rapamycin pretreatment. Taken together, rapamycin pretreatment may alleviate cerebral I/R injury partly through inhibiting autophagic activities and NFκB pathways in rats.

Bardoxolone Ameliorates Cerebral Ischemia/ Reperfusion Injury in Male Rats

2019 ◽  
Vol 22 (04) ◽  
pp. 122-130
Author(s):  
Rihab H Al-Mudhaffer ◽  
Laith M Abbas Al-Huseini ◽  
Saif M Hassan ◽  
Najah R Hadi
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Male Rats ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury
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