Abstract 2981: Neuroprotective Effect Of Acute Ethanol Administration In Rat With Transient Cerebral Ischemia

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Xiaokun Geng ◽  
Xunming Ji ◽  
Fei Wang ◽  
Yu Wang ◽  
Karam ASMARO ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Acute Ischemic Stroke ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Elevated Serum ◽  
Transient Cerebral Ischemia ◽  
Alcoholic Beverages ◽  
Ethanol Administration ◽  
Lesion Volume

Background and Purpose _ Despite a focus on the pathological effects of alcohol abuse, numerous studies published over the past several decades also demonstrate beneficial effects of light-to-moderate consumption of alcoholic beverages. Recent studies have demonstrated that elevated serum ethanol levels are associated with increased survival in patients with traumatic brain injury (TBI), suggesting that an acute exposure to alcohol exerts a neuroprotective effect. In a rat model of transient cerebral ischemia, we identified administration of ethanol as a possible treatment for acute ischemic stroke. Methods _Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for two hours. Five sets of experiments were conducted: 1) to determine the dose-response effect of ethanol (0.5, 1.0 and 1.5g/kg) on brain infarction and functional outcome; 2) to determine whether combining ethanol (1.5g/kg) and hypothermia produces synergistic neuroprotection; 3) to determine the therapeutic windows of opportunity for ethanol in stroke; to test whether ethanol promotes intracerebral hemorrhage (ICH) in hemorrhagic or ischemic stroke, or after administration of thrombolytics in ischemic stroke; and 5) to test the affect of ethanol on HIF-1α protein expression. Results —Ethanol at 1.5 g/kg, which produce blood levels (89mg/dL) within the legally intoxicated range for driving (80-100 g/dL), most effectively reduced infarct volume and behavioral dysfunction when administered at 2, 3 or 4 hours after MCAO. We find that ethanol and moderate hypothermia (32-34 °C) exert neuroprotective effects of similar magnitude at both the lesion volume and functional levels, but do not exert a synergistic effect in this model. Ethanol did not promote cerebral hemorrhage in hemorrhagic or ischemic stroke in combination with recombinant tissue plasminogen activator (rt-PA) or urokinase (UK). Up-regulation of HIF-1α protein levels was enhanced by ethanol, in association with reduced brain infarct volume and improved functional recovery in rats subjected to stroke using the same dose (1.5 g/kg). Conclusions —Ethanol exerts a strong neuroprotective effect when administered up to 4 hours after ischemia, and does not promote ICH when used with thrombolytics. Ethanol is a potential neuroprotectant for acute ischemic stroke.

Abstract WP62: Enhanced Neuroprotection of Normobaric Oxygenation with Ethanol Conferred by Apoptosis Reduction in Acute Ischemic Stroke

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Sweena Parmar ◽  
Xiaokun Geng ◽  
Changya Peng ◽  
Murali Guthikonda ◽  
Yuchuan Ding
Keyword(s):  
Cell Death ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Neuroprotective Effect ◽  
Apoptotic Cell Death ◽  
Ethanol Administration ◽  
Sprague Dawley ◽  
Apoptotic Proteins

Objectives: Normobaric oxygenation (NBO) has been shown to provide neuroprotection in vivo and in vitro . Yet, a recent Phase 2 clinical trial investigating NBO therapy in acute ischemic stroke was terminated due to questionable therapeutic benefit. NBO therapy alone may be insufficient to produce improved outcomes. In our recent study, we demonstrated a strong neuroprotective effect of ethanol at a dose of 1.5 g/kg (equivalent to the human legal driving limit). In this study, we sought to identify whether low-dose ethanol administration enhances the neuroprotection offered by NBO and whether combined administration of NBO with ethanol is associated with reduced apoptosis. Methods: Sprague-Dawley rats were subjected to right middle cerebral artery occlusion (MCAO) for 2 h, followed by reperfusion. Ischemic animals received either an intraperitoneal injection of 1.0 g/kg ethanol, 2 h of 100% NBO, or both ethanol and NBO. The Cell Death Detection ELISA Assay (Roche) was performed to determine apoptotic cell death at 24 h after reperfusion. Levels of pro-apoptotic (Caspase-3, Bcl-2-associated X-BAX, and Apoptosis-Inducing Factor-AIF) and anti-apoptotic proteins (Bcl-2 and Bcl-xL) were determined by Western blot analysis at 3 and 24 h after reperfusion. Results: As expected, untreated ischemic rats had the highest apoptotic cell death. Combined NBO/ethanol therapy decreased cell death by 48%, as compared to 29% with ethanol and 22% with NBO. Similarly, combined NBO/ethanol therapy promoted the greatest expression of anti-apoptotic factors and the lowest expression of pro-apoptotic proteins at 3 h after reperfusion. This effect was maintained at 24 h and even more pronounced for AIF and Caspase-3. Conclusions: Given singularly, NBO and ethanol improved the degree of cell death, decreased the expression of pro-apoptotic proteins, and increased the expression of anti-apoptotic proteins. Yet, when administered together, their effects largely compounded. These results suggest a synergistic neuroprotection offered by NBO with ethanol, which may be attributed at least in part to their shared role in modulating neuronal apoptosis.

Neuroprotective effect of ginkgolide K against acute ischemic stroke on middle cerebral ischemia occlusion in rats

2011 ◽  
Vol 66 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Shuwei Ma ◽  
Huafeng Yin ◽  
Lvyi Chen ◽  
Hongxia Liu ◽  
Ming Zhao ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Acute Ischemic Stroke ◽  
Neuroprotective Effect

Impact of Collateral Status on Neuroprotective Effect of Cyclosporine A in Acute Ischemic Stroke

2019 ◽  
Vol 16 (2) ◽  
pp. 173-177
Author(s):  
Norbert Nighoghossian ◽  
Lucie Cornut ◽  
Camille Amaz ◽  
Omer Eker ◽  
Nathan Mewton ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Cyclosporine A ◽  
Neuroprotective Effect ◽  
Additional Benefit ◽  
Lesion Volume ◽  
Dynamic Susceptibility ◽  
Collateral Flow ◽  
Dynamic Susceptibility Contrast ◽  
Ischemic Lesion

Background: Neuroprotection for acute ischemic stroke remains an elusive goal. Intracranial collaterals may favor neuroprotective drugs delivery at the acute stage of ischemic stroke. A recent phase 2 study showed that cyclosporine A (CsA) reduced ischemic damage in patients with a proximal occlusion who experienced effective recanalization. Collateral flow may improve this benefit. Materials & Methods: Collateral supply was assessed using dynamic susceptibility contrast MRI in 47 patients among the 110 patients from the original study and were graded in two groups: good collaterals and poor collaterals. Patients with good collaterals had significantly smaller initial infarct in both CsA group (p = 0.003) and controls (p = 0.016). Similarly, the final lesion volume was significantly lower in patients with good collaterals in both groups. Results: In patients with either good or poor collaterals CsA showed no additional benefit on ischemic lesion progression and final infarct size at day 30. Conclusion: We failed to demonstrate any significant additional benefit of CsA in patients with good collateral circulation.

scholarly journals Neuroprotective Effect of Acute Ethanol Administration in a Rat With Transient Cerebral Ischemia

Stroke ◽  
2012 ◽  
Vol 43 (1) ◽  
pp. 205-210 ◽  
Author(s):  
Fei Wang ◽  
Yu Wang ◽  
Xiaokun Geng ◽  
Karam Asmaro ◽  
Changya Peng ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Neuroprotective Effect ◽  
Transient Cerebral Ischemia ◽  
Ethanol Administration ◽  
Acute Ethanol

High Prestroke Physical Activity Is Associated with Reduced Infarct Growth in Acute Ischemic Stroke Patients Treated with Intravenous tPA and Randomized to Remote Ischemic Perconditioning

2017 ◽  
Vol 44 (1-2) ◽  
pp. 88-95 ◽  
Author(s):  
Rolf A. Blauenfeldt ◽  
Kristina D. Hougaard ◽  
Kim Mouridsen ◽  
Grethe Andersen
Keyword(s):  
Physical Activity ◽  
Ischemic Stroke ◽  
Infarct Size ◽  
Acute Ischemic Stroke ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Intravenous Thrombolysis ◽  
Stroke Patients ◽  
Remote Ischemic Perconditioning ◽  
Final Infarct Size

Background: A high prestroke physical activity (PA) level is associated with reduced stroke rate, stroke mortality, better functional outcome, and possible neuroprotective abilities. The aim of the present study was to examine the possible neuroprotective effect of prestroke PA on 24-h cerebral infarct growth in a cohort of acute ischemic stroke patients treated with intravenous tPA and randomized to remote ischemic perconditioning. Methods: In this predefined subanalysis, data from a randomized clinical trial investigating the effect of remote ischemic perconditioning (RIPerC) on AIS was used. Prestroke (7 days before admission) PA was quantified using the PA Scale for the Elderly (PASE) questionnaire at baseline. Infarct growth was evaluated using MRI (acute, 24-h, and 1-month). Results: PASE scores were obtained from 102 of 153 (67%) patients with a median (interquartile range) age of 66 (58-73) years. A high prestroke PA level correlated significantly with reduced acute infarct growth (24 h) in the linear regression model (4th quartile prestroke PA level compared with the 1st quartile), β4th quartile = -0.82 (95% CI -1.54 to -0.10). However, the effect of prestroke PA was present mainly in patients randomized to RIPerC, β4th quartile = -1.14 (95% CI -2.04 to -0.25). In patients randomized to RIPerC, prestroke PA was a predictor of final infarct size (1-month infarct volume), β4th quartile = -1.78 (95% CI -3.15 to -0.41). Conclusion: In AIS patients treated with RIPerC, as add-on to intravenous thrombolysis, the level of PA the week before the stroke was associated with decreased 24-h infarct growth and final infarct size. These results are highly encouraging and stress the need for further exploration of the potentially protective effects of both PA and remote ischemic conditioning.

scholarly journals Mucosal‐Associated Invariant T Cells Are Involved in Acute Ischemic Stroke by Regulating Neuroinflammation

2021 ◽  
Author(s):  
Sho Nakajima ◽  
Ryota Tanaka ◽  
Kazuo Yamashiro ◽  
Asako Chiba ◽  
Daisuke Noto ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Acute Ischemic Stroke ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Flow Cytometric Analysis ◽  
Interleukin 17 ◽  
Ischemic Brain ◽  
Mait Cells ◽  
Acute Cerebral Ischemia

Background Mucosal‐associated invariant T (MAIT) cells have been associated with inflammation in several autoimmune diseases. However, their relation to ischemic stroke remains unclear. This study attempted to elucidate the role of MAIT cells in acute ischemic stroke in mice. Methods and Results We used MR1 knockout C57BL/6 (MR1 −/− ) mice and wild‐type littermates (MR1 +/+ ). After performing a transient middle cerebral artery occlusion (tMCAO), we evaluated the association with inflammation and prognosis in the acute cerebral ischemia. Furthermore, we analyzed the tMCAO C57BL/6 mice administered with the suppressive MR1 ligand and the vehicle control. We also evaluated the infiltration of MAIT cells into the ischemic brain by flow cytometry. Results showed a reduction of infarct volume and an improvement of neurological impairment in MR1 −/− mice (n=8). There was a reduction in the number of infiltrating microglia/macrophages (n=3–5) and in their activation (n=5) in the peri‐infarct area of MR1 −/− mice. The cytokine levels of interleukin‐6 and interleukin‐17 at 24 hours after tMCAO (n=3–5), and for interleukin‐17 at 72 hours after tMCAO (n=5), were lower in the MR1 −/− mice. The administration of the suppressive MR1 ligand reduced the infarct volume and improved functional impairment (n=5). Flow cytometric analysis demonstrated there was a reduction of MAIT cells infiltrating into the ischemic brain at 24 hours after tMCAO (n=17). Conclusions Our results showed that MAIT cells play an important role in neuroinflammation after focal cerebral ischemia and the use of MAIT cell regulation has a potential role as a novel neuroprotectant for the treatment of acute ischemic stroke.

Neuroprotective effect of osthole against acute ischemic stroke on middle cerebral ischemia occlusion in rats

2010 ◽  
Vol 1363 ◽  
pp. 206-211 ◽  
Author(s):  
Xiaodong Chao ◽  
Jun Zhou ◽  
Tao Chen ◽  
Wenbo Liu ◽  
Wenpeng Dong ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Acute Ischemic Stroke ◽  
Neuroprotective Effect

scholarly journals Endocannabinoid response in acute ischemic stroke: elevated 2-arachidonoylglycerol

2020 ◽  
Author(s):  
Marina Buciuc ◽  
Gian Marco Conte ◽  
Eugene L. Scharf
Keyword(s):  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Acute Ischemic Stroke ◽  
Symptom Onset ◽  
Therapeutic Potential ◽  
Infarct Volume ◽  
Closed Head Injury ◽  
Acute Cerebral Ischemia ◽  
Ischemic Attack

ABSTRACTBackground and purposeEndocannabinoids are hypothesized to have anti-inflammatory and neuroprotective properties and hold therapeutic potential in the acute phase response mechanisms during acute cerebral ischemia and closed head injury. We set to describe the plasma levels of endocannabinoids and related ethanolamides during acute and subacute phases of cerebral ischemia.MethodsWe conducted a prospective observational study of plasma endocannabinoid levels in patients with acute ischemic stroke or transient ischemic attack. Two blood samples were collected: T1 (<12 hours from symptom onset) and T2 (>24 hours from symptom onset). N-arachidonoylethanolamine (AEA), 2-arachidonoylglycerol (2-AG), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) were quantified by liquid chromatography mass spectrometry.ResultsTwenty-three patients met inclusion criteria. Median (interquartile range): Age – 76 years (60-81); body mass index - 25.6 (23.6-30.4); National Institutes of Health Stroke Scale score-5(3-13); infarct volume - 1.4 cm3 (0.5-8.6). Higher 2-AG levels at T1 were correlated with smaller infarct volumes (Spearman ƿ=-0.48, p=0.0206). Levels of 2-AG were elevated at T2 compared to T1 in 48% of patients (median difference - 310.3nM, 95% CI 194.1-497.3; p=0.001); AEA, PEA and OEA did not differ between T1 and T2, p>0.05. Patients with elevated 2-AG at T2 had larger infarct volumes, p=0.0178, lower frequency of embolectomy performed, p=0.0373, but no difference in neurological disability 90 days after the ischemic event compared to patients without 2-AG elevation.Conclusion2-AG increases significantly in early phases of ischemic stroke. The final mechanistic role of 2-AG in acute ischemic stroke is to be determined in further studies.

scholarly journals Timely and Appropriate Administration of Inhaled Argon Provides Better Outcomes for tMCAO Mice: a Controlled, Randomized and Double-blind Animal Study

2021 ◽  
Author(s):  
Juan He ◽  
Ke Xue ◽  
Jiayi Liu ◽  
Jin-hua Gu ◽  
Bin Peng ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Brain Edema ◽  
Infarct Volume ◽  
Inert Gases ◽  
Neurological Deficits ◽  
Lesion Volume ◽  
Double Blind ◽  
Neuroprotective Agent ◽  
Neuroprotective Efficacy

Abstract Background: Inhaled argon (iAr) has shown promising therapeutic efficacy for acute ischemic stroke (AIS) and exhibited impressive advantages over other inert gases as a neuroprotective agent. However, the optimal dose, duration and time point of iAr for AIS are unknown. Here, we explored variable iAr schedules and evaluated the neuroprotective effects of acute iAr administration on lesion volume, brain edema, and neurological function in a mouse model of cerebral ischemic/reperfusion (I/R) injury.Methods: Adult ICR mice were randomly subjected to sham, moderate (1.5 h) or severe (3 h) transient middle cerebral artery occlusion (tMCAO). One hour after tMCAO, the mice were randomized to variable iAr protocols or air (iCtr). General and focal deficit scores were assessed during double-blind treatment. Infarct volume, overall recovery and brain edema were analyzed 24 h after cerebral I/R injury.Results: Compared with those in the tMCAO only group, lesion volume (p<0.001) and neurologic outcome (general, p<0.001; focal, p<0.001) were significantly improved in the iAr group, which was assigned to argon inhalation 1 h after ischemia (before the onset of reperfusion). Short-term argon treatment (1 h or 3 h) showed significantly better outcomes with regard to infarct volume (p<0.01) compared to argon inhalation for 24 h. The concentration of argon inhalation was confirmed to be a key factor in improving the focal neurological outcome relative to that in the tMCAO group, and higher concentrations showed better effects. In addition, even though ischemia research has shown an increase in cerebral damage proportional to ischemia time, argon administration showed significant neuroprotective efficacy on infarct volume (p<0.001), neurological deficits (general, p<0.001; focal, p<0.001), weight recovery (p<0.001), and edema (p<0.001) in general, particularly in moderate stroke.Conclusions: Timely argon inhalation before the onset of reperfusion showed optimal neurological outcomes and minimal infarct volumes. Moreover, an appropriate duration of argon administration was important for better neuroprotective efficacy. These findings may provide vital guidance for using argon as a neuroprotective agent and moving to clinical trials in acute ischemic stroke.

scholarly journals PKA-Dependent Membrane Surface Recruitment of CI-AMPARs Is Crucial for BCP-Mediated Protection Against Post-acute Ischemic Stroke Cognitive Impairment

2020 ◽  
Vol 11 ◽  
Author(s):  
Sha Chen ◽  
Yuchun Wang ◽  
Xuhui Wang ◽  
Meng He ◽  
Lu Zhang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cognitive Impairment ◽  
Acute Ischemic Stroke ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Membrane Surface ◽  
Synaptic Membranes ◽  
Synaptic Membrane ◽  
Membrane Expression ◽  
Pka Pathway

Post-acute ischemic stroke cognitive impairment frequently occurs and seriously affects patients daily activities. Recruitment of GluA2-containing Ca2+-impermeable AMPA receptors (CI-AMPARs) to hippocampal synaptic membrane surfaces was shown to trigger synaptic plasticity. Currently, the effect of CI-AMPAR trafficking on acute ischemic stroke remains poorly understood. β-Caryophyllene (BCP) has been shown to ameliorate cognitive impairment. However, the mechanism has not been characterized. In this study, a 60-min temporary middle cerebral artery occlusion (MCAO) model was established to simulate the pathology of acute ischemic stroke. BCP reduced neurologic deficits, cerebral infarct volume, and pathological damage in MCAO mice and caused CI-AMPARs to translocate to synaptic membranes in the hippocampus; surface expression of CI-AMPARs was also decreased in MCAO mice. Furthermore, this study also showed that BCP treatment significantly activated the cAMP/PKA pathway, which is consistent with the synaptic membrane expression of CI-AMPARs. To better understand the underlying mechanisms, the PKA inhibitor H-89 was used to study the role of BCP in MCAO mice. Interestingly, H-89 treatment significantly disrupted the BCP-mediated facilitation of CI-AMPAR translocation to the synaptic membrane surface and substantially attenuated BCP-induced protection against acute ischemic stroke. Additionally, inhibition the cAMP/PKA pathway not only reduced BCP-induced inhibition of AMPAR-mediated excitatory postsynaptic currents in the hippocampal CA1 region but also decreased the effect of BCP-mediated protection against post-acute ischemic stroke cognitive impairment. Taken together, these data indicate that PKA-dependent synaptic membrane surface recruitment of CI-AMPARs is crucial for the neuroprotective effect of BCP against acute ischemic stroke and protection against post-acute ischemic stroke cognitive impairment.

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