Changes in Extracellular Glutamate Release on Repetitive Transient Occlusion in Global Ischemia Model

2009 ◽  
Author(s):  
Gija Lee ◽  
Seokkeun Choi ◽  
Sungwook Kang ◽  
Samjin Choi ◽  
Jeonghoon Park ◽  
...  
Keyword(s):  
Neuronal Damage ◽  
Glutamate Release ◽  
Short Interval ◽  
Neuronal Cell ◽  
Release Time ◽  
Protective Mechanism ◽  
Time Interval ◽  
Extracellular Glutamate ◽  
Vessel Occlusion ◽  
Doppler Flowmetry

During the operation, surgeons in neurosurgical area usually performed the multiple temporary occlusions of parental artery which may induce the neuronal damage. It is generally thought that neuronal damage by cerebral ischemia is associated with extracellular concentrations of the excitatory amino acids. In this experiment, we measured the dynamics of extracellular glutamate release in 11 vessel occlusion (VO) model during repeated within short interval. Changes in cerebral blood flow were monitored by laser-Doppler flowmetry simultaneously with cortical glutamate level measured by amperometric biosensor. During ischemia, the peak level of glutamate release was gradually decreased as 112.38±26.21 μM in first period, 82.63±18.50 μM in second period, and 48.58±11.89 μM in third period. The time interval between the ischemia induction and the beginning of glutamate release was increased as 106.7 ± 10.89 (sec) at first attack, 139.11 ± 3.87 (sec) in second attack, 169.00 ± 14.56 (sec) in third ischemic period. From the results of real-time monitoring about glutamate release in 11-VO model during repetitive ischemic episode, it was demonstrated that repetitive ischemia induced less glutamate release from neuronal cell than single ischemia due to endogeneous protective mechanism which delayed glutamate release time in later ischemic injury.

Correlation between extracellular glutamate release and neuronal cell death in an eleven vessel occlusion model in rat

2010 ◽  
Vol 1342 ◽  
pp. 160-166 ◽  
Author(s):  
Eunkuk Park ◽  
Gi Ja Lee ◽  
Samjin Choi ◽  
Seok Keun Choi ◽  
Su Jin Chae ◽  
...  
Keyword(s):  
Cell Death ◽  
Glutamate Release ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Extracellular Glutamate ◽  
Vessel Occlusion ◽  
Occlusion Model

scholarly journals Lipid Peroxidation in Chronic Cerebral HypoperfusionInduced Neurodegeneration in Rats

2020 ◽  
Vol 10 (2) ◽  
Author(s):  
Anil Kumar S ◽  
Saif SA ◽  
Oothuman P ◽  
Mustafa MIA
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lipid Peroxidation ◽  
Neurodegenerative Disorders ◽  
Neuronal Damage ◽  
Neuronal Cell ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Control Group ◽  
Vessel Occlusion

Introduction: Reduced cerebral blood fl ow is associated with neurodegenerative disorders and dementia, in particular. Experimental evidence has demonstrated the initiating role of chronic cerebral hypoperfusion in neuronal damage to the hippocampus, the cerebral cortex, the white matter areas and the visual system. Permanent, bilateral occlusion of the common carotid arteries of rats (two vessel occlusion - 2VO) has been introduced for the reproduction of chronic cerebral hypoperfusion as it occurs in Alzheimer’s disease and human aging. Increased generation of free radicals through lipid peroxidation can damage neuronal cell membrane. Markers of lipid peroxidation have been found to be elevated in brain tissues and body fl uids in neurodegenerative diseases, including Alzheimer’s disease, Parkinson disease and amyotrophic lateral sclerosis. Materials and Methods: Malondialdehyde (MDA), final product of lipid peroxidation, was estimated by thiobarbituric acid-reactive substances (TBARS) assay kit at eight weeks after induction of 2VO in the rats and control group. Results: Our study revealed a highly signifi cant (p<0.001) increase in the mean MDA concentration (12.296 ± 1.113 μM) in 2VO rats as compared to the control group (5.286 ± 0.363 μM) rats. Conclusion: Therapeutic strategies to modulate lipid peroxidation early throughout the course of the disease may be promising in slowing or possibly preventing neurodegenerative disorders.

scholarly journals Resveratrol Promotes Mitochondrial Biogenesis and Protects against Seizure-Induced Neuronal Cell Damage in the Hippocampus Following Status Epilepticus by Activation of the PGC-1α Signaling Pathway

2019 ◽  
Vol 20 (4) ◽  
pp. 998 ◽  
Author(s):  
Yao-Chung Chuang ◽  
Shang-Der Chen ◽  
Chung-Yao Hsu ◽  
Shu-Fang Chen ◽  
Nai-Ching Chen ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
Signaling Pathway ◽  
Mitochondrial Biogenesis ◽  
Neuronal Damage ◽  
Cell Damage ◽  
Neuroprotective Effect ◽  
Neuronal Cell ◽  
Protective Mechanism ◽  
Protective Effects ◽  
Prolonged Seizure

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is known to regulate mitochondrial biogenesis. Resveratrol is present in a variety of plants, including the skin of grapes, blueberries, raspberries, mulberries, and peanuts. It has been shown to offer protective effects against a number of cardiovascular and neurodegenerative diseases, stroke, and epilepsy. This study examined the neuroprotective effect of resveratrol on mitochondrial biogenesis in the hippocampus following experimental status epilepticus. Kainic acid was microinjected into left hippocampal CA3 in Sprague Dawley rats to induce bilateral prolonged seizure activity. PGC-1α expression and related mitochondrial biogenesis were investigated. Amounts of nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (Tfam), cytochrome c oxidase 1 (COX1), and mitochondrial DNA (mtDNA) were measured to evaluate the extent of mitochondrial biogenesis. Increased PGC-1α and mitochondrial biogenesis machinery after prolonged seizure were found in CA3. Resveratrol increased expression of PGC-1α, NRF1, and Tfam, NRF1 binding activity, COX1 level, and mtDNA amount. In addition, resveratrol reduced activated caspase-3 activity and attenuated neuronal cell damage in the hippocampus following status epilepticus. These results suggest that resveratrol plays a pivotal role in the mitochondrial biogenesis machinery that may provide a protective mechanism counteracting seizure-induced neuronal damage by activation of the PGC-1α signaling pathway.

Alterations in τ Immunostaining in the Rat Hippocampus following Transient Cerebral Ischemia

1994 ◽  
Vol 14 (4) ◽  
pp. 554-564 ◽  
Author(s):  
James W. Geddes ◽  
Claudia Schwab ◽  
Susan Craddock ◽  
Janice L. Wilson ◽  
L. Creed Pettigrew
Keyword(s):  
Neuronal Damage ◽  
Hippocampal Formation ◽  
Molecular Layer ◽  
Neuronal Cell ◽  
Direct Result ◽  
Ischemic Insult ◽  
Vessel Occlusion ◽  
Neuronal Populations ◽  
Neuronal Cell Bodies ◽  
Hilar Neurons

Previous studies in gerbils have shown that cytoskeletal disruption and a loss of the dendritic microtubule-associated protein, MAP2, may occur after short periods of transient global ischemia. τ, a predominantly axonal microtubule-associated protein, has not been examined following ischemia. We compared neuronal damage with alterations in MAP2, τ, and 72-kD heat shock protein (HSP72) immunostaining at various reperfusion times following 20 min of ischemia in the rat four-vessel occlusion model. τ accumulated in neuronal cell bodies throughout the hippocampal formation 30 min to 2 h after the ischemic insult. Perikaryal τ immunostaining was transient in most regions, but persisted in polymorphic hilar neurons. This was accompanied by a loss of immunostaining in the target of many hilar neurons, the inner molecular layer of the dentate gyrus. The same neuronal populations that exhibited increased τ immunostaining of perikarya later displayed an induction of HSP72 immunoreactivity. In contrast, loss of MAP2 immunostaining was not consistently observed before neuronal death and did not correspond to HSP72 induction. The altered τ immunostaining is not the direct result of excitotoxic insult, as intrahippocampal injection of kainic acid did not cause the somal accumulation of τ, but did cause disruption of MAP2 immunostaining. Taken together, the results suggest that the somal accumulation of τ is an early, sensitive, and selective marker of ischemic insult.

A use-dependent sodium channel antagonist, 619C89, in reduction of ischemic brain damage and glutamate release after acute subdural hematoma in the rat

1996 ◽  
Vol 85 (1) ◽  
pp. 104-111 ◽  
Author(s):  
Eiji Tsuchida ◽  
John F. Harms ◽  
John J. Woodward ◽  
Ross Bullock
Keyword(s):  
Sodium Channel ◽  
Subdural Hematoma ◽  
Neuronal Damage ◽  
Glutamate Release ◽  
Acute Subdural Hematoma ◽  
Extracellular Glutamate ◽  
Ischemic Brain ◽  
Content Type ◽  
Glutamate Concentration ◽  
Fine Print

✓ Acute subdural hematoma kills or disables more severely head injured patients than any other complication of cranial trauma. The main pathological factor involved is ischemic neuronal damage, which is caused by raised intracranial pressure and local effect. The authors have evaluated the hypothesis that a novel use-dependent sodium channel antagonist, 619C89, could reduce ischemic brain damage in the rat subdural hematoma model. Because previous studies have shown that focal neuronal damage may be mediated by “excitotoxic” mechanisms, and because excitatory amino acid levels have been shown to be markedly elevated after brain trauma in humans, the authors have measured levels of glutamate, aspartate, and threonine within the cortex underneath the hematoma, using in vivo microdialysis before and after induction of hematoma, in both vehicle- and drug-treated rats. Postinjury treatment with 619C89 (30 mg/kg) significantly reduced the volume of hemispheric ischemic damage produced by subdural hematoma, from 99.77 ± 7.51 mm3 in vehicle-treated control rats to 46.07 ± 11.06 mm3 (p = 0.0007) in drug-treated animals. In the vehicle-treated animals, induction of subdural hematoma led to a fourfold increase in glutamate in the first 30 minutes after subdural hematoma occurred. The mean extracellular glutamate concentration in these animals remained 2- to 2.6-fold increased over the following 2.5 hours. In the 619C89-treated animals, the release of glutamate from the cortex underneath the hematoma was significantly attenuated. In these rats, induction of subdural hematoma led to a 2.7-fold increase in the first 30-minute sample, but extracellular glutamate concentration returned to near-basal levels thereafter, compared with vehicle-treated animals (p < 0.05). These results show that 619C89 is highly neuroprotective in this model and that its effects may, in part, be mediated by the inhibiton of glutamate release from the ischemic cortex underneath the hematoma.

scholarly journals Immunocytochemical Study of an Early Microglial Activation in Ischemia

1992 ◽  
Vol 12 (2) ◽  
pp. 257-269 ◽  
Author(s):  
Jochen Gehrmann ◽  
Petra Bonnekoh ◽  
Takahito Miyazawa ◽  
Konstantin-Alexander Hossmann ◽  
Georg W. Kreutzberg
Keyword(s):  
Monoclonal Antibodies ◽  
Distribution Pattern ◽  
Rat Brain ◽  
Mhc Class Ii ◽  
Neuronal Damage ◽  
Dorsal Hippocampus ◽  
Neuronal Cell ◽  
Microglial Cells ◽  
Vessel Occlusion ◽  
Temporal And Spatial Distribution

Transient arrest of the cerebral blood circulation results in neuronal cell death in selectively vulnerable regions of the rat brain. To elucidate further the involvement of glial cells in this pathology, we have studied the temporal and spatial distribution pattern of activated microglial cells in several regions of the ischemic rat brain. Transient global ischemia was produced in rats by 30 min of a four-vessel occlusion. Survival times were 1, 3, and 7 days after the ischemic injury. The microglial reaction was studied immunocytochemically using several monoclonal antibodies, e.g., against CR3 complement receptor and major histocompatibility complex (MHC) antigens. Two recently produced monoclonal antibodies against rat microglial cells, designated MUC 101 and 102, were also used to identify microglial cells. Following ischemia, the microglial reaction was correlated with the development of neuronal damage. The earliest presence of activated microglial cells was observed in the dorsolateral striatum, the CA1 area, and the dentate hilus of the dorsal hippocampus. However, the microglial reaction was not confined to areas showing selective neuronal damage, but also occurred in regions that are rather resistant to ischemia, such as the CA3 area. Particularly in the frontoparietal cortex, the appearance of MHC class II–positive microglial cells provided an early indication of the subsequent distribution pattern of neuronal damage. The microglial reaction would thus seem to be an early, sensitive, and reliable marker for the occurrence of neuronal damage in ischemia.

scholarly journals Direct Evidence for Acute and Massive Norepinephrine Release in the Hippocampus during Transient Ischemia

1989 ◽  
Vol 9 (6) ◽  
pp. 892-896 ◽  
Author(s):  
Mordecai Y.-T. Globus ◽  
Raul Busto ◽  
W. Dalton Dietrich ◽  
Elena Martinez ◽  
Isabel Valdés ◽  
...  
Keyword(s):  
Direct Evidence ◽  
Neuronal Damage ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Fold Increase ◽  
Norepinephrine Release ◽  
Transient Ischemia ◽  
Vessel Occlusion ◽  
Extracellular Release ◽  
Induced Changes

Recent studies suggest the norepinephrine (NE) may play a regulatory role in neuronal cell death in the hippocampus after transient ischemia. However, ischemia-induced changes in extracellular NE release have not been demonstrated. In the present study, we utilized the microdialysis technique to measure extracellular NE levels in the hippocampus before, during, and after 20 min of global ischemia induced by two-vessel occlusion combined with systemic hypotension in the rat. Stable basal concentrations of extracellular NE were detected in three consecutive samples collected prior to ischemia (1.86 ± 1.21 pmol/ml of perfusate mean ± SEM). During ischemia, NE levels increased to 30.1 ± 5.5 pmol/ml, representing an 18-fold increase. The levels gradually returned to baseline by 40 min of reperfusion. These results are the first to demonstrate that acute and massive extracellular release of NE occurs in the hippocampus during ischemia and early recirculation. These results support the hypothesis that the activation of the noradrenergic system may play a significant role in modulating the development of ischemic neuronal damage.

scholarly journals Icaritin Alleviates Glutamate-Induced Neuronal Damage by Inactivating GluN2B-Containing NMDARs Through the ERK/DAPK1 Pathway

2021 ◽  
Vol 15 ◽  
Author(s):  
Song Liu ◽  
Chaoming Liu ◽  
Lijiao Xiong ◽  
Jiali Xie ◽  
Cheng Huang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Cortical Neurons ◽  
Neuronal Damage ◽  
Glutamate Release ◽  
Specific Inhibitor ◽  
Expression Level ◽  
Protective Mechanism ◽  
Pathophysiological Mechanism ◽  
Neuroprotective Effects ◽  
Primary Cortical Neurons

Excitatory toxicity due to excessive glutamate release is considered the core pathophysiological mechanism of cerebral ischemia. It is primarily mediated by N-methyl-D-aspartate receptors (NMDARs) on neuronal membranes. Our previous studies have found that icaritin (ICT) exhibits neuroprotective effects against cerebral ischemia in rats, but the underlying mechanism is unclear. This study aims to investigate the protective effect of ICT on glutamate-induced neuronal injury and uncover its possible molecular mechanism. An excitatory toxicity injury model was created using rat primary cortical neurons treated with glutamate and glycine. The results showed that ICT has neuroprotective effects on glutamate-treated primary cortical neurons by increasing cell viability while reducing the rate of lactate dehydrogenase (LDH) release and reducing apoptosis. Remarkably, ICT rescued the changes in the ERK/DAPK1 signaling pathway after glutamate treatment by increasing the expression levels of p-ERK, p-DAPK1 and t-DAPK1. In addition, ICT also regulates NMDAR function during glutamate-induced injury by decreasing the expression level of the GluN2B subunit and enhancing the expression level of the GluN2A subunit. As cotreatment with the ERK-specific inhibitor U0126 and ICT abolishes the beneficial effects of ITC on the ERK/DAPK1 pathway, NMDAR subtypes and neuronal cell survival, ERK is recognized as a crucial mediator in the protective mechanism of ICT. In conclusion, our findings demonstrate that ICT has a neuroprotective effect on neuronal damage induced by glutamate, and its mechanism may be related to inactivating GluN2B-containing NMDAR through the ERK/DAPK1 pathway. This study provides a new clue for the prevention and treatment of clinical ischemic cerebrovascular diseases.

scholarly journals Neurotoxicity of Clostridium perfringensEpsilon-Toxin for the Rat Hippocampus via the Glutamatergic System

1998 ◽  
Vol 66 (6) ◽  
pp. 2501-2508 ◽  
Author(s):  
Osamu Miyamoto ◽  
Junzaburo Minami ◽  
Tetsuhiko Toyoshima ◽  
Takehiro Nakamura ◽  
Tetsuya Masada ◽  
...  
Keyword(s):  
Neuronal Damage ◽  
Glutamate Release ◽  
Lethal Dose ◽  
Pyramidal Cells ◽  
Histological Change ◽  
Sublethal Dose ◽  
Glutamatergic System ◽  
Doppler Flowmetry ◽  
Dark Cells ◽  
Epsilon Toxin

ABSTRACT The neurotoxicity of epsilon-toxin, one of the major lethal toxins produced by Clostridium perfringens type B, was studied by histological examination of the rat brain. When the toxin was injected intravenously at a lethal dose (100 ng/kg), neuronal damage was observed in many areas of the brain. Injection of the toxin at a sublethal dose (50 ng/kg) caused neuronal damage predominantly in the hippocampus: pyramidal cells in the hippocampus showed marked shrinkage and karyopyknosis, or so-called dark cells. The dark cells lost the immunoreactivity to microtubule-associated protein-2, a postsynaptic somal and dendric marker, while acetylcholinesterase-positive fibers were not affected. Timm’s zinc staining revealed that zinc ions were depleted in the mossy layers of the CA3 subfield containing glutamate as a synaptic transmitter. The cerebral blood flow in the hippocampus was not altered significantly before or after administration of the toxin, as measured by laser-Doppler flowmetry, excluding the possibility that the observed histological change was due to a secondary effect of ischemia in the hippocampus. Prior injection of either a glutamate release inhibitor or a glutamate receptor antagonist protected the hippocampus from the neuronal damage caused by epsilon-toxin. These results suggest that epsilon-toxin acts on the glutamatergic system and evokes excessive release of glutamate, leading to neuronal damage.

Real-World Experience with Artificial Intelligence-Based Triage in Transferred Large Vessel Occlusion Stroke Patients

2021 ◽  
pp. 1-6
Author(s):  
Jacob R. Morey ◽  
Xiangnan Zhang ◽  
Kurt A. Yaeger ◽  
Emily Fiano ◽  
Naoum Fares Marayati ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Clinical Outcomes ◽  
Warning System ◽  
Large Vessel ◽  
Time Interval ◽  
Large Vessel Occlusion ◽  
Time Intervals ◽  
Vessel Occlusion ◽  
Left Behind ◽  
Stroke Center

<b><i>Background and Purpose:</i></b> Randomized controlled trials have demonstrated the importance of time to endovascular therapy (EVT) in clinical outcomes in large vessel occlusion (LVO) acute ischemic stroke. Delays to treatment are particularly prevalent when patients require a transfer from hospitals without EVT capability onsite. A computer-aided triage system, Viz LVO, has the potential to streamline workflows. This platform includes an image viewer, a communication system, and an artificial intelligence (AI) algorithm that automatically identifies suspected LVO strokes on CTA imaging and rapidly triggers alerts. We hypothesize that the Viz application will decrease time-to-treatment, leading to improved clinical outcomes. <b><i>Methods:</i></b> A retrospective analysis of a prospectively maintained database was assessed for patients who presented to a stroke center currently utilizing Viz LVO and underwent EVT following transfer for LVO stroke between July 2018 and March 2020. Time intervals and clinical outcomes were compared for 55 patients divided into pre- and post-Viz cohorts. <b><i>Results:</i></b> The median initial door-to-neuroendovascular team (NT) notification time interval was significantly faster (25.0 min [IQR = 12.0] vs. 40.0 min [IQR = 61.0]; <i>p</i> = 0.01) with less variation (<i>p</i> &#x3c; 0.05) following Viz LVO implementation. The median initial door-to-skin puncture time interval was 25 min shorter in the post-Viz cohort, although this was not statistically significant (<i>p</i> = 0.15). <b><i>Conclusions:</i></b> Preliminary results have shown that Viz LVO implementation is associated with earlier, more consistent NT notification times. This application can serve as an early warning system and a failsafe to ensure that no LVO is left behind.

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