scholarly journals Early Reperfusion Following Ischemic Stroke Provides Beneficial Effects, Even After Lethal Ischemia with Mature Neural Cell Death

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1374 ◽  
Author(s):  
Yasue Tanaka ◽  
Nami Nakagomi ◽  
Nobutaka Doe ◽  
Akiko Nakano-Doi ◽  
Toshinori Sawano ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Artery Occlusion ◽  
Neural Cells ◽  
Stroke Patients ◽  
Early Reperfusion ◽  
Beneficial Effects ◽  
Cerebral Artery Occlusion

Ischemic stroke is a critical disease caused by cerebral artery occlusion in the central nervous system (CNS). Recent therapeutic advances, such as neuroendovascular intervention and thrombolytic therapy, have allowed recanalization of occluded brain arteries in an increasing number of stroke patients. Although previous studies have focused on rescuing neural cells that still survive despite decreased blood flow, expanding the therapeutic time window may allow more patients to undergo reperfusion in the near future, even after lethal ischemia, which is characterized by death of mature neural cells, such as neurons and glia. However, it remains unclear whether early reperfusion following lethal ischemia results in positive outcomes. The present study used two ischemic mouse models—90-min transient middle cerebral artery occlusion (t-MCAO) paired with reperfusion to induce lethal ischemia and permanent middle cerebral artery occlusion (p-MCAO)—to investigate the effect of early reperfusion up to 8 w following MCAO. Although early reperfusion following 90-min t-MCAO did not rescue mature neural cells, it preserved the vascular cells within the ischemic areas at 1 d following 90-min t-MCAO compared to that following p-MCAO. In addition, early reperfusion facilitated the healing processes, including not only vascular but also neural repair, during acute and chronic periods and improved recovery. Furthermore, compared with p-MCAO, early reperfusion after t-MCAO prevented behavioral symptoms of neurological deficits without increasing negative complications, including hemorrhagic transformation and mortality. These results indicate that early reperfusion provides beneficial effects presumably via cytoprotective and regenerative mechanisms in the CNS, suggesting that it may be useful for stroke patients that experienced lethal ischemia.

THE RELATIONSHIP BETWEEN TIMING OF RECANALIZATION AND CLINICAL OUTCOME OF ISCHEMIC STROKE DUE TO ACUTE MIDDLE CEREBRAL ARTERY OCCLUSION AFTER ULTRASOUND-ENHANCED THROMBOLYSIS

2017 ◽  
pp. 38-43
Author(s):  
Quang Thang Tran ◽  
Dat Anh Nguyen ◽  
Van Chi Nguyen ◽  
Duy Ton Mai ◽  
Van Thinh Le
Keyword(s):  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Recombinant Tissue Plasminogen Activator ◽  
Artery Occlusion ◽  
Stroke Patients ◽  
Tissue Plasminogen ◽  
Cerebral Artery Occlusion ◽  
The Relationship

Purpose: The relationship between arterial recanalization after use of intravenous recombinant tissue plasminogen activator (rtPA) and outcome is still uncertain. The aim of our study was to evaluate the association between the timing and impact of recanalization on functional outcomes in ischemic stroke patients due to acute middle cerebral artery occlusion. Subjects and methods: Nonrandomized 40 stroke patients with proximal middle arterial occlusion on a prebolus TCD receiving intravenously 0.6 mg/kg rtPA within 4.5 hours after stroke onset were monitored with portable diagnostic TCD equipment and a standard headframe. Complete recanalization was defined as thrombolysis in brain ischemia (TIBI) flow grades 4-5. Results: 40 patients (mean age 67±14 years, NIH Stroke Scale [NIHSS] 16.15±8.6 points) were treated at 180±80 minutes from symptom onset. TCD was monitored continously for 120 minutes. Complete recanalization on TCD within 2 hours after bolus was found in 13 patients (32.5%). In this group, NIHSS decreased quickly at 2 hours and 24 hours. Modified Rankins 0-1point was seen in 92.3% of patients with complete recanalization compared to 37.0% of patients with uncomplete recanalization at 90 days. Non-symptomatic intracranial hemorrhage was seen in 1 patient in the group of complete recanalization. Conclusions: Complete recanalization of middle cerebral arteries within 2 hours after IV rtPA treatment plays a role in predicting the good functional and clinical outcomes after ultrasound-enhanced thrombolysis in acute ischemic stroke patients due to acute middle cerebral artery occlusion. Key words: stroke, recombinant tissue plasminogen activator, transcranial Doppler sonography

scholarly journals Post-Ischemic Helium Provides Neuroprotection in Rats Subjected to Middle Cerebral Artery Occlusion-Induced Ischemia by Producing Hypothermia

2009 ◽  
Vol 29 (6) ◽  
pp. 1159-1165 ◽  
Author(s):  
Hélène N David ◽  
Benoît Haelewyn ◽  
Laurent Chazalviel ◽  
Myriam Lecocq ◽  
Mickael Degoulet ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Acute Ischemic Stroke ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Artery Occlusion ◽  
Inert Gases ◽  
Clinical Use ◽  
Early Reperfusion ◽  
Cerebral Artery Occlusion

During the past decade, studies on the manipulation of various inhaled inert gases during ischemia and/or reperfusion have led to the conclusion that inert gases may be promising agents for treating acute ischemic stroke and perinatal hypoxia-ischemia insults. Although there is a general consensus that among these gases xenon is a golden standard, the possible widespread clinical use of xenon experiences major obstacles, namely its availability and cost of production. Interestingly, recent findings have shown that helium, which is a cost-efficient inert gas with no anesthetic properties, can provide neuroprotection against acute ischemic stroke in vivo when administered during ischemia and early reperfusion. We have investigated whether helium provides neuroprotection in rats subjected to middle cerebral artery occlusion (MCAO) when administered after reperfusion, a condition prerequisite for the therapeutic viability and possible clinical use of helium. In this study, we show that helium at 75 vol% produces neuroprotection and improvement of neurologic outcome in rats subjected to transient MCAO by producing hypothermia on account of its high specific heat as compared with air.

Abstract 166: Endothelial Overexpression of LOX-1 Increases Stroke Size in vivo

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Alexander Akhmedov ◽  
Remo D Spescha ◽  
Francesco Paneni ◽  
Giovani G Camici ◽  
Thomas F Luescher
Keyword(s):  
Endothelial Cells ◽  
Ischemic Stroke ◽  
Endothelial Dysfunction ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Oxidized Ldl ◽  
Artery Occlusion ◽  
Cerebral Artery Occlusion ◽  
The Brain

Background— Stroke is one of the most common causes of death and long term disability worldwide primarily affecting the elderly population. Lectin-like oxidized LDL receptor 1 (LOX-1) is the receptor for oxidized LDL identified in endothelial cells. Binding of OxLDL to LOX-1 induces several cellular events in endothelial cells, such as activation of transcription factor NF-kB, upregulation of MCP-1, and reduction in intracellular NO. Accumulating evidence suggests that LOX-1 is involved in endothelial dysfunction, inflammation, atherogenesis, myocardial infarction, and intimal thickening after balloon catheter injury. Interestingly, a recent study demonstrated that acetylsalicylic acid (aspirin), which could prevent ischemic stroke, inhibited Ox-LDL-mediated LOX-1 expression in human coronary endothelial cells. The expression of LOX-1 was increased at a transient ischemic core site in the rat middle cerebral artery occlusion model. These data suggest that LOX-1 expression induces atherosclerosis in the brain and is the precipitating cause of ischemic stroke. Therefore, the goal of the present study was to investigate the role of endothelial LOX-1 in stroke using experimental mouse model. Methods and Results— 12-week-old male LOX-1TG generated recently in our group and wild-type (WT) mice were applied for a transient middle cerebral artery occlusion (MCAO) model to induce ischemia/reperfusion (I/R) brain injury. LOX-1TG mice developed 24h post-MCAO significantly larger infarcts in the brain compared to WT (81.51±8.84 vs. 46.41±10.13, n=7, p < 0.05) as assessed morphologically using Triphenyltetrazolium chloride (TTC) staining. Moreover, LOX-1TG showed higher neurological deficit in RotaRod (35.57±8.92 vs. 66.14±10.63, n=7, p < 0.05) and Bederson tests (2.22±0.14 vs. 1.25±0.30, n=9-12, p < 0.05) - two experimental physiological tests for neurological function. Conclusions— Thus, our data suggest that LOX-1 plays a critical role in the ischemic stroke when expressed at unphysiological levels. Such LOX-1 -associated phenotype could be due to the endothelial dysfunction. Therefore, LOX-1 may represent novel therapeutic targets for preventing ischemic stroke.

scholarly journals A Novel Model for Encephalomyosynangiosis Surgery after Middle Cerebral Artery Occlusion-Induced Stroke in Mice

2021 ◽  
Author(s):  
Mitch Paro ◽  
Daylin Gamiotea Turro ◽  
Leslie Blumenfeld ◽  
Ketan R Bulsara ◽  
Rajkumar Verma
Keyword(s):  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Artery Occlusion ◽  
Novel Treatment ◽  
Graft Tissue ◽  
Cerebral Artery Occlusion

Background and Purpose: No effective treatment is available for most patients who suffer ischemic stroke. Development of novel treatment options is imperative. The brain attempts to self-heal after ischemic stroke via various mechanism mediated by restored blood circulation in affected region of brain but this process is limited by inadequate angiogenesis or neoangiogenesis. Encephalomyosynangiosis (EMS) is a neurosurgical procedure that achieves angiogenesis with low morbidity in patients with moyamoya disease, reducing risk of stroke. However, EMS, surgery has never been studied as an therapeutic option after ischemic stroke. Here we described a novel procedure and feasibility data for EMS after ischemic stroke in mice. Methods: A 60 mins of middle cerebral artery occlusion (MCAo) was used to induce ischemic stroke in mice. After 3-4 hours of MCAo onset/sham, EMS was performed. Mortality of EMS, MCAo and. MCAo+EMS mice was recorded up to 21 days after surgery. Graft tissue viability was measured using a nicotinamide adenine dinucleotide reduced tetrazolium reductase assay. Results: EMS surgery after ischemic stroke does not increase mortality compared to stroke alone. Graft muscle tissue remained viable 21 days after surgery. Conclusions: This novel protocol is effective and well-tolerated, may serve as novel platform for new angiogenesis and thus recovery after ischemic stroke. If successful in mice, EMS can a very feasible and novel treatment option for ischemic stroke in humans.

Abstract TP106: Automated Assessment of Behavioral Function After Experimental Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Terrance Chiang ◽  
Sean Harvey ◽  
Arjun V Pendharkar ◽  
Michelle Y Cheng ◽  
Gary K Steinberg
Keyword(s):  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Artery Occlusion ◽  
Motor Deficit ◽  
Motor Deficits ◽  
Stroke Models ◽  
Cerebral Artery Occlusion ◽  
Significant Motor

Introduction: Manual scoring of behavior tests is commonly used for assessing motor deficits after stroke, however, it is labor intensive and subject to bias. These limitations lead to inconsistent assessment between research groups and non-reproducible data. In this study, we investigated the feasibility of an automated motor deficit assessment system, Erasmus ladder, in two ischemic stroke models. Methods: Distal middle cerebral artery occlusion (dMCAO n=10) or transient middle cerebral artery occlusion (tMCAO 30 minutes, n=15) were performed on male C57BL6J mice (11-13 weeks) to generate cortical ischemic stroke, with. Naïve mice (n=10) were used as controls. Immunohistochemistry was performed on brains collected at post-stroke day (PD) 30 to assess for infarct size (MAP2) and inflammation (CD68). Mice without infarct in both cortex and striatum were excluded from the study. Behavior was assessed using Erasmus ladder at pre-stroke baseline (4 unperturbed and 4 perturbed sessions) and on PD 7, 14, 21, and 28 (all perturbed sessions). Results: Erasmus ladder detected significant motor deficits in the tMCAO model, specifically in the pre- and post- perturbed times as well as several key step types (HH long). Analyses in the tMCAO model reveal changes in various step patterns and their capability to react to the perturbation (obstacle). These significant motor deficits after tMCAO were detectable until PD28. We also observed a sustained decline in the use of affected limb compared to unaffected limb until PD28. While this trend is also present in dMCAO model, motor deficits were detected in the dMCAO only at early timepoints (PD7) and the difference subsided by PD28. Conclusion: We have assessed the data collected by Erasmus ladder on mice that underwent two commonly used stroke models (tMCAO and dMCAO). Our data showed that Erasmus ladder can detect long term motor deficit including reduced use of affected limb, step pattern, and motor reaction to obstacle. This automated instrument is effective in detecting motor deficits in the tMCAO model and thus, can be used to evaluate treatments for enhancing recovery after stroke.

Early Reperfusion in the Anesthetized Baboon Reduces Brain Damage Following Middle Cerebral Artery Occlusion

Stroke ◽  
1997 ◽  
Vol 28 (3) ◽  
pp. 632-638 ◽  
Author(s):  
Alan R. Young ◽  
Omar Touzani ◽  
Jean-Michel Derlon ◽  
Giuliano Sette ◽  
Eric T. MacKenzie ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Brain Damage ◽  
Cerebral Artery ◽  
Artery Occlusion ◽  
Early Reperfusion ◽  
Cerebral Artery Occlusion

scholarly journals Benefit of endovascular thrombectomy for M2 middle cerebral artery occlusion in the ARISE II study

2020 ◽  
pp. neurintsurg-2020-016427
Author(s):  
Adam de Havenon ◽  
Ana Paula Narata ◽  
Aymeric Amelot ◽  
Jeffrey L Saver ◽  
Hormozd Bozorgchami ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Adverse Events ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Scale Score ◽  
Cerebral Artery ◽  
Artery Occlusion ◽  
Endovascular Thrombectomy ◽  
Good Outcome ◽  
Cerebral Artery Occlusion

BackgroundThe benefit of endovascular thrombectomy for acute ischemic stroke with M2 segment middle cerebral artery occlusion remains controversial, with uncertainty and paucity of data specific to this population.ObjectiveTo compare outcomes between M1 and M2 occlusions in the Analysis of Revascularization in Ischemic Stroke with EmboTrap (ARISE II) trial.MethodsWe performed a prespecified analysis of the ARISE II trial with the primary outcome of 90-day modified Rankin Scale score of 0–2, which we termed good outcome. Secondary outcomes included reperfusion rates and major adverse events. The primary predictor was M2 occlusion, which we compared with M1 occlusion.ResultsWe included 183 patients, of whom 126 (69%) had M1 occlusion and 57 (31%) had M2 occlusion. There was no difference in the reperfusion rates or adverse events between M2 and M1 occlusions. The rate of good outcome was not different in M2 versus M1 occlusions (70.2% vs 69.7%, p=0.946). In a logistic regression model adjusted for age, sex, and baseline National Institutes of Health Stroke Scale score, M2 occlusions did not have a significantly different odds of good outcome compared with M1 occlusions (OR 0.94, 95% CI 0.47 to 1.88, p=0.87).ConclusionIn ARISE II, M2 occlusions achieved a 70.2% rate of good outcome at 90 days, which is above published rates for untreated M2 occlusions and superior to prior reports of M2 occlusions treated with endovascular thrombectomy. We also report similar rates of good outcome, successful reperfusion, death, and other adverse events when comparing the M1 and M2 occlusions.

scholarly journals Alleviation of Cerebral Infarction of Rats With Middle Cerebral Artery Occlusion by Inhibition of Aquaporin 4 in the Supraoptic Nucleus

ASN NEURO ◽  
2020 ◽  
Vol 12 ◽  
pp. 175909142096055 ◽  
Author(s):  
Dan Cui ◽  
Shuwei Jia ◽  
Jiawei Yu ◽  
Dongyang Li ◽  
Tong Li ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Infarction ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Supraoptic Nucleus ◽  
Artery Occlusion ◽  
Aquaporin 4 ◽  
Vasopressin Neurons ◽  
Cerebral Artery Occlusion

In ischemic stroke, vasopressin hypersecretion is a critical factor of cerebral swelling and brain injury. To clarify neural mechanisms underlying ischemic stroke-evoked vasopressin hypersecretion, we observed the effect of unilateral permanent middle cerebral artery occlusion (MCAO) in rats on astrocytic plasticity and vasopressin neuronal activity in the supraoptic nucleus (SON) as well as their associated cerebral injuries. MCAO for 8 hr caused cerebral infarction in the MCAO side where water contents also increased. Immunohistochemical examination revealed that the percentage of phosphorylated extracellular signal-regulated protein kinase 1/2 (pERK1/2)-positive vasopressin neurons in the SON of MCAO side was significantly higher than that in non-MCAO side and in sham group. In the cortex, pERK1/2 and aquaporin 4 expressions increased significantly in the infarction area, while glial fibrillary acidic protein (GFAP) reduced significantly compared with the noninfarction side in brain cortex. Microinjection of N-(1,3,4-Thiadiazolyl)nicotinamide-020 [TGN-020, a specific blocker of aquaporin 4] into the SON blocked MCAO-evoked increases in pERK1/2 in the SON as well as the reduction of GFAP and the increase in pERK1/2 and aquaporin 4 in the infarction area of the cortex. Finally, oxygen and glucose deprivation reduced GFAP expression and the colocalization and molecular association of GFAP with aquaporin 4 in the SON in brain slices. These effects were blocked by TGN-020 and/or phloretin, a blocker of astrocytic volume-regulated anion channels. These findings indicate that blocking aquaporin 4 in the SON may reduce the activation of vasopressin neurons and brain injuries elicited by vasopressin during ischemic stroke.

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