scholarly journals Neuroprotection by glutamate oxaloacetate transaminase in ischemic stroke: An experimental study

2011 ◽  
Vol 31 (6) ◽  
pp. 1378-1386 ◽  
Author(s):  
Francisco Campos ◽  
Tomás Sobrino ◽  
Pedro Ramos-Cabrer ◽  
Bárbara Argibay ◽  
Jesús Agulla ◽  
...  
Keyword(s):  
Animal Model ◽  
Ischemic Stroke ◽  
Arterial Occlusion ◽  
Brain Parenchyma ◽  
Resonance Spectroscopy ◽  
Glutamate Oxaloacetate Transaminase ◽  
Neuroprotective Effects ◽  
Sensorimotor Deficits ◽  
Cerebral Arterial Occlusion ◽  
The Brain

As ischemic stroke is associated with an excessive release of glutamate into the neuronal extracellular space, a decrease in blood glutamate levels could provide a mechanism to remove it from the brain tissue, by increasing the brain-blood gradient. In this regard, the ability of glutamate oxaloacetate transaminase (GOT) to metabolize glutamate in blood could represent a potential neuroprotective tool for ischemic stroke. This study aimed to determine the neuroprotective effects of GOT in an animal model of cerebral ischemia by means of a middle cerebral arterial occlusion (MCAO) following the Stroke Therapy Academic Industry Roundtable (STAIR) group guidelines. In this animal model, oxaloacetate-mediated GOT activation inhibited the increase of blood and cerebral glutamate after MCAO. This effect is reflected in a reduction of infarct size, smaller edema volume, and lower sensorimotor deficits with respect to controls. Magnetic resonance spectroscopy confirmed that the increase of glutamate levels in the brain parenchyma after MCAO is inhibited after oxaloacetate-mediated GOT activation. These findings show the capacity of the GOT to remove glutamate from the brain by means of blood glutamate degradation, and suggest the applicability of this enzyme as an efficient and novel neuroprotective tool against ischemic stroke.

scholarly journals Measurement of the Intracranial Arterial Wedge Pressure in Cases of Acute Cerebral Arterial Occlusion to Determine the Indication of Intraarterial Thrombolytic Therapy

2000 ◽  
Vol 6 (1_suppl) ◽  
pp. 213-215
Author(s):  
T. Terada ◽  
M. Tsuura ◽  
H. Matsumoto ◽  
O. Masuo ◽  
G. Hyotani ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Ischemic Stroke ◽  
Thrombolytic Therapy ◽  
Arterial Occlusion ◽  
Time Loss ◽  
Cerebral Arterial Occlusion ◽  
The Relationship ◽  
The Brain ◽  
Wedge Pressure

Wedge pressure of the occluded major cerebral artery (distal pressure beyond the occlusion) was measured to estimate the residual cerebral blood flow in thirteen patients with acute ischemic stroke. There existed the relationship that patients with higher wedge pressure tolerated longer ischemic insults than those with lower wedge pressure. Wedge pressure is measured with minimum time loss before starting thrombolytic therapy and may be a good indicator to estimate the brain tissue reversibility.

Abstract WP24: Improvement In Collateral Score And Level Of Occlusion Are Early Angiographic Indicators Of The Degree of Infarction In Acute Ischemic Stroke

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Matthew R Amans ◽  
Maya Vella ◽  
Daniel L Cooke ◽  
Steven W Hetts
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Brain Infarction ◽  
Arterial Occlusion ◽  
Brain Parenchyma ◽  
Post Intervention ◽  
Vessel Occlusion ◽  
Post Procedure ◽  
Before And After ◽  
Cerebral Arterial Occlusion

INTRODUCTION: Brain parenchyma contrast staining on CT after recanalization therapy and digital subtraction angiography (DSA) in large vessel occlusion acute ischemic stroke (LVO-AIS) patients has been demonstrated to be a marker for significant brain injury, possibly indicating blood brain barrier breakdown or no-reflow phenomena at the capillary level. Most often stained parenchyma undergoes infarction. We evaluated several DSA parameters in order to determine if findings on DSA at the time of LVO-AIS intervention can predict postintervention parenchymal contrast staining on CT and, thus, serve as early prognostic factors for brain infarction. HYPOTHESIS: Point of cerebral arterial occlusion, TICI score, and degree of pial collateraliation correlate with presence of parenchymal contrast staining on post-intervention CT in LVO-AIS patients. METHODS: Our institution’s CHR approved this analysis of imaging and patient charts. We reviewed 17 years of LVO-AIS intervention at our institution, and 67 patients met inclusion criteria. Angiograms were evaluated for level of occlusion, TICI scores before and after intervention, and level of collateralization before and after intervention. Statistical analysis was performed using Fisher’s exact test and ANOVA. RESULTS: More proximal sites of cerebral arterial occlusion were more likely patients to have post-intervention staining (p=0.08). Preprocedure TICI, postprocedure TICI and improvement in TICI score did not predict contrast staining on post procedure CT (p=0.34, 0.54, and 0.52). Preprocedure collateral score, post procedure collateral score were similarly not predictive (p=0.28 and 0.93). Decreasing collateral score (i.e., increased antegrade flow with decreased need for collateral supply) was predictive of contrast staining (p=0.09). CONCLUSION: Improvement in pial collateral score was more predictive of postprocedure contrast staining than was change in TICI grade, and thus may serve as a complement to TICI in the assessment of revascularization efficacy at the time of stroke intervention.

Neuroprotection via AT2 receptor agonists in ischemic stroke

2018 ◽  
Vol 132 (10) ◽  
pp. 1055-1067 ◽  
Author(s):  
Douglas M. Bennion ◽  
U. Muscha Steckelings ◽  
Colin Sumners
Keyword(s):  
Ischemic Stroke ◽  
Neuronal Damage ◽  
Recombinant Tissue Plasminogen Activator ◽  
Neurological Deficits ◽  
At2 Receptor ◽  
Neuroprotective Effects ◽  
Receptor Agonists ◽  
Stroke Epidemiology ◽  
The Brain

Stroke is a devastating disease that afflicts millions of people each year worldwide. Ischemic stroke, which accounts for ~88% of cases, occurs when blood supply to the brain is decreased, often because of thromboembolism or atherosclerotic occlusion. This deprives the brain of oxygen and nutrients, causing immediate, irreversible necrosis within the core of the ischemic area, but more delayed and potentially reversible neuronal damage in the surrounding brain tissue, the penumbra. The only currently approved therapies for ischemic stroke, the thrombolytic agent recombinant tissue plasminogen activator (rtPA) and the endovascular clot retrieval/destruction processes, are aimed at restoring blood flow to the infarcted area, but are only available for a minority of patients and are not able in most cases to completely restore neurological deficits. Consequently, there remains a need for agents that will protect neurones against death following ischemic stroke. Here, we evaluate angiotensin II (Ang II) type 2 (AT2) receptor agonists as a possible therapeutic target for this disease. We first provide an overview of stroke epidemiology, pathophysiology, and currently approved therapies. We next review the large amount of preclinical evidence, accumulated over the past decade and a half, which indicates that AT2 receptor agonists exert significant neuroprotective effects in various animal models, and discuss the potential mechanisms involved. Finally, after discussing the challenges of delivering blood–brain barrier (BBB) impermeable AT2 receptor agonists to the infarcted areas of the brain, we summarize the evidence for and against the development of these agents as a promising therapeutic strategy for ischemic stroke.

Neutrophil affinity for PGP and HAIYPRH (T7) peptide dual-ligand functionalized nanoformulation enhances the brain delivery of tanshinone IIA and exerts neuroprotective effects against ischemic stroke by inhibiting proinflammatory signaling pathways

2018 ◽  
Vol 42 (23) ◽  
pp. 19043-19061
Author(s):  
Yutao Li ◽  
Chiying An ◽  
Danan Han ◽  
Yanxin Dang ◽  
Xin Liu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Physicochemical Properties ◽  
Signaling Pathways ◽  
Blood Brain Barrier ◽  
Tanshinone Iia ◽  
Brain Barrier ◽  
Brain Delivery ◽  
Neuroprotective Effects ◽  
The Poor ◽  
The Brain

A great challenge to the therapy of ischemic stroke is the poor physicochemical properties and inability of the drug to cross the blood–brain barrier (BBB).

scholarly journals Measurement of cerebrovascular reserve by multimodal imaging for cerebral arterial occlusion or stenosis patients: protocol of a prospective, randomized, controlled clinical trial

2019 ◽  
Author(s):  
xiao zhipeng ◽  
ji ke ◽  
lin yong ◽  
wan jieqing ◽  
pan yaohua ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Ischemic Stroke ◽  
Arterial Occlusion ◽  
Transluminal Angioplasty ◽  
Cerebrovascular Reactivity ◽  
Stroke Recurrence ◽  
Controlled Clinical Trial ◽  
Cerebrovascular Reserve ◽  
Randomized Controlled ◽  
Cerebral Arterial Occlusion

Abstract Background Cerebrovascular reactivity (CVR), index of cerebral hemodynamics, might guide the treatment of ischemic stroke. However, the previous studies that the therapeutic strategy of stroke mainly depends on the degree of vascular stenosis with steady-state vascular parameters, such as cerebral blood flow, and CVR factors are not under consideration. Measurement of CVR by multimodal image might improve the prognosis for ischemic stroke. Methods/design The study is a prospective, randomized, paralleled controlled clinical trial to examine the multimodal image evaluation for CVR. A total of 66 eligible patients will be recruited from Renji hospital, Shanghai Jiaotong University School of Medicine. The patients will be categorized based on CVR into two subgroups as follows: CVR>10% group and CVR<10% group. And the patients will be randomly assigned to medical management, percutaneous transluminal angioplasty and stenting, and intracranial and extra-cranial bypass groups in a 1:1:1 ratio. The primary end point is all adverse events and ipsilateral stroke recurrence at 6, 12, 24 months after the management. The secondary outcomes include the CVR, the National Institute of Health stroke scale and the Modified Rankin Scale at 6, 12, 24 months. Discussion Measurement of cerebrovascular reserve by multimodal image is recommended by most recent studies to guide the treatment of ischemic stroke, and thus its efficacy and evaluation accuracy need to be established in randomized controlled settings. This prospective, randomized, paralleled controlled registry study, together with other ongoing studies, will present more evidence for optimal individualized accurate treatment of ischemic stroke.

An Angiopep-2 functionalized nanoformulation enhances brain accumulation of tanshinone IIA and exerts neuroprotective effects against ischemic stroke

2018 ◽  
Vol 42 (21) ◽  
pp. 17359-17370 ◽  
Author(s):  
Yutao Li ◽  
Yanxin Dang ◽  
Dandan Han ◽  
Yong Tan ◽  
Xin Liu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Tanshinone Iia ◽  
Effective Intervention ◽  
Neuroprotective Effects ◽  
Neuroprotective Drugs ◽  
The Brain

Effective intervention against ischemic stroke requires delivery of potent neuroprotective drugs to the brain.

ADAMTS13 Gene Deletion Aggravates Ischemic Brain Damage

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 260-260 ◽  
Author(s):  
Kenji Nishio ◽  
Masayuki Fujioka ◽  
Kazuhide Hayakawa ◽  
Kenichi Mishima ◽  
Michihiro Fujiwara ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Arterial Occlusion ◽  
Neurological Deficits ◽  
Doppler Flowmetry ◽  
Adamts13 Deficiency ◽  
Cerebral Arterial Occlusion ◽  
The Brain

Abstract Background: The proteolytic activity of human ADAMTS13 regulates the size of von Willebrand factor (VWF) multimers, controlling excessive platelet aggregation and preventing microvascular thrombus formation. Deficiency of ADAMTS13 causes thrombotic thrombocytopenic purpura (TTP) and patients with TTP often have neurological deficits such as stupor or coma. Therefore, ADAMTS13 appears necessary for vascular homeostasis in the brain and may also influence the response to brain injury during ischemic stroke. Method and Result: We investigated the role of ADAMTS13 in a mouse middle cerebral arterial occlusion (MCAO) model of ischemia-reperfusion injury in the brain. We compared 24 wild type mice (WT) and 24 ADAMTS13 gene deleted mice (KO), which are healthy and fertile. All mice were males 6–8 weeks of age. Investigators were blinded to the genotype until all analyses were finished. We applied MCAO for 30 minutes followed by 23.5 hours of reperfusion. The cerebral blood flow (CBF) around the cortex of the ischemic region was measured by laser Doppler flowmetry for 60 minutes after MCAO. In both WT and KO mice, the CBF decreased to less than 20% of baseline during MCAO and returned to normal immediately after reperfusion. However, during the subsequent 30 min the CBF decreased to 34.6±5.8% of baseline for KO mice compared to 83.2±6.8% of baseline for WT mice (P &lt; 0.01) and remained significantly decreased at 24 hours, suggesting that ADAMTS13 deficiency promotes thrombosis after reperfusion injury. The infarction volumes of the brain were determined from the area not stained by 2,3,5,-triphenyltetrazolium chloride (TTC) 24 hours after MCAO. KO mice had significantly increased volume of brain infarction compared with WT (31.0±6.5mm3 vs 11.4±1.9 mm3, P &lt; 0.01). The degree of post-ischemic inflammation was estimated by Western blotting of plasma HMGB1 (high-mobility group box1) 24 hours after MCAO. Plasma HMGB1 was increased to 34.4 ± 5.3 ng/ml in KO mice, compared to 19.6 ± 3.5 ng/ml in WT mice (P &lt; 0.05). The KO and WT mice did not differ during the MCAO procedure in body temperature, survival (80% vs 85%) at 24 hours, prothrombin time, arterial pH, pO2 or pCO2. Conclusion: ADAMTS13 deficiency aggravates the extent of persistent brain ischemia, infarct volume and inflammatory response after brief MCAO. Therefore, ADAMTS13 plays a neuroprotective role against ischemia-reperfusion injury.

scholarly journals Intravenous Thrombolysis in Ischemic Stroke Patients with Intracranial Neoplasms: Two Cases and a Literature Review

2011 ◽  
Vol 2011 ◽  
pp. 1-3 ◽  
Author(s):  
William Neil ◽  
Bruce Ovbiagele
Keyword(s):  
Ischemic Stroke ◽  
Intravenous Thrombolysis ◽  
Recombinant Tissue Plasminogen Activator ◽  
Brain Parenchyma ◽  
Intracranial Neoplasms ◽  
First Case ◽  
Tissue Plasminogen ◽  
Acoustic Schwannoma ◽  
Brain Parenchymal ◽  
The Brain

Based on exclusion criteria in the landmark NINDS-rtPA trial, current expert consensus guidelines preclude the use of intravenous recombinant tissue plasminogen activator (IV rtPA) in acute ischemic stroke (AIS) patients with intracranial neoplasm. There are only 3 published cases of administration of IV rtPA to AIS patients with intracranial neoplasms in the literature. Two of these published cases involved malignant brain parenchymal lesions discovered only after rtPA was inadvertently given, and one of these cases was associated with hemorrhage within the tumor. In this paper, we report two cases of administration of IV rtPA in AIS patients with intracranial neoplasms observed on neuroimaging prior to IV rtPA administration. In both cases, the tumor was outside of the brain parenchyma. The first case was an acoustic schwannoma and the second a falcine meningioma. Neither case was associated with intratumoral hemorrhage as of at least one week following IV rtPA treatment. More published cases are definitely warranted, but our experience with these two cases suggests that administration of IV rtPA to AIS patients in the presence of extraparenchymal brain tumors may not necessarily precipitate intra-tumoral bleeding and thereby worsen clinical outcomes.

scholarly journals The Role of Urocortins in Intracerebral Hemorrhage

Biomolecules ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 96 ◽  
Author(s):  
Ker Woon Choy ◽  
Andy Po-Yi Tsai ◽  
Peter Bor-Chian Lin ◽  
Meng-Yu Wu ◽  
Chihyi Lee ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Brain Regions ◽  
Brain Parenchyma ◽  
Protective Mechanisms ◽  
Neuroprotective Effects ◽  
Blood Brain Barrier Disruption ◽  
Brain Barrier Disruption ◽  
G Protein Coupled ◽  
The Brain

Intracerebral hemorrhage (ICH) causes an accumulation of blood in the brain parenchyma that disrupts the normal neurological function of the brain. Despite extensive clinical trials, no medical or surgical therapy has shown to be effective in managing ICH, resulting in a poor prognosis for the patients. Urocortin (UCN) is a 40-amino-acid endogenous neuropeptide that belongs to the corticotropin-releasing hormone (CRH) family. The effect of UCN is activated by binding to two G-protein coupled receptors, CRH-R1 and CRH-R2, which are expressed in brain neurons and glial cells in various brain regions. Current research has shown that UCN exerts neuroprotective effects in ICH models via anti-inflammatory effects, which generally reduced brain edema and reduced blood-brain barrier disruption. These effects gradually help in the improvement of the neurological outcome, and thus, UCN may be a potential therapeutic target in the treatment of ICH. This review summarizes the data published to date on the role of UCN in ICH and the possible protective mechanisms underlined.

scholarly journals Sustained blood glutamate scavenging enhances protection in ischemic stroke

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Ahlem Zaghmi ◽  
Antonio Dopico-López ◽  
María Pérez-Mato ◽  
Ramón Iglesias-Rey ◽  
Pablo Hervella ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Infarct Volume ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Treated Group ◽  
The Body ◽  
Glutamate Oxaloacetate Transaminase ◽  
Glutamate Scavenging ◽  
Blood Glutamate Scavenging ◽  
The Brain

AbstractStroke is a major cause of morbidity, mortality, and disability. During ischemic stroke, a marked and prolonged rise of glutamate concentration in the brain causes neuronal cell death. This study explores the protective effect of a bioconjugate form of glutamate oxaloacetate transaminase (hrGOT), which catalyzes the depletion of blood glutamate in the bloodstream for ~6 days following a single administration. When treated with this bioconjugate, a significant reduction of the infarct volume and a better retention of sensorimotor function was observed for ischemic rats compared to those treated with saline. Moreover, the equivalent dose of native hrGOT yielded similar results to the saline treated group for some tests. Targeting the bioconjugate to the blood-brain-barrier did not improve its performance. The data suggest that the bioconjugates draw glutamate out of the brain by displacing homeostasis between the different glutamate pools of the body.

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