scholarly journals Estradiol Attenuates Neuroprotective Benefits of Isoflurane Preconditioning in Ischemic Mouse Brain

2008 ◽  
Vol 28 (11) ◽  
pp. 1824-1834 ◽  
Author(s):  
Lan Wang ◽  
Hideto Kitano ◽  
Patricia D Hurn ◽  
Stephanie J Murphy
Keyword(s):  
Infarct Volume ◽  
Artery Occlusion ◽  
Experimental Stroke ◽  
Ischemic Damage ◽  
Triphenyltetrazolium Chloride ◽  
Anesthetic Preconditioning ◽  
Infarction Volume ◽  
Male Specific ◽  
Cerebral Artery Occlusion

Isoflurane preconditioning (IsoPC) neuroprotection in experimental stroke is male-specific. We determined whether estradiol alters ischemic outcomes in IsoPC brain and examined the role of estrogen receptors (ERs). Seven to 10 days before preconditioning, ovariectomized (OVX) mice were implanted with estradiol, vehicle, or ER subtype agonists. OVX ± estradiol, OVX ± vehicle, OVX ± ER agonists, and ER subtype wild-type (WT) and knockout (KO) mice were preconditioned for 4 h with sham anesthetic preconditioning (sham PC) or 1% IsoPC and recovered for 24 h. Mice then underwent 2 h of middle cerebral artery occlusion followed by 22 h of reperfusion. Infarct volumes were determined by 2,3,5-triphenyltetrazolium chloride staining, with comparisons between IsoPC and corresponding sham PC for each treatment group. Decreased infarct injury was seen in IsoPC OVX ± vehicle, whereas estradiol in IsoPC OVX mice enhanced ischemic damage. In ER studies, increased infarct volumes were seen in IsoPC ERWT mice regardless of ER subtype. IsoPC in ERαKO mice had no effect on infarction volume but reduced only cortical ischemic damage in ERβKO mice. In OVX + ERβ agonist, IsoPC had no effect on infarction volume. In OVX + ER/α agonist, IsoPC increased cortical infarct volume. Estradiol depresses the brain's protective response to IsoPC and may exacerbate cortical ischemic injury mainly through an ERβ-dependent mechanism.

Abstract WP118: The Flavanol (-)-Epicatechin Improves Functional Recovery In Mice Subjected To Experimental Stroke

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Christopher C Leonardo ◽  
Sean Robbins ◽  
Abdullah A Ahmad ◽  
Sylvain Dore
Keyword(s):  
Functional Recovery ◽  
Transcriptional Activation ◽  
Infarct Volume ◽  
Epidemiological Studies ◽  
Artery Occlusion ◽  
Experimental Stroke ◽  
Adhesive Tape ◽  
Dietary Consumption ◽  
Therapeutic Doses ◽  
Cerebral Artery Occlusion

Background: Epidemiological studies indicate that flavanol consumption reduces the propensity to develop cerebrovascular disease. Available data suggest actions on multiple pro-inflammatory pathways, yet it remains unclear which pathways mediate functional recovery after stroke. Our goal is to begin identifying the mechanisms by which the flavanol (-)-epicatechin (EC) improves anatomical and functional outcomes. Based upon data from initial dose-response experiments, ongoing studies are investigating hypothesized protective pathways involving matrix metalloproteinase-mediated blood brain barrier protection and Nrf2 transcriptional activation. Methods: Male, 8-10wk old C57BL/6 mice were pretreated with EC 90m prior to permanent distal middle cerebral artery occlusion. Vehicle or EC was administered by oral gavage to mimic dietary consumption. Mice were evaluated 1, 4 and 7d post-stroke for performance on various sensorimotor tasks prior to histological assessments. Results: Initial experiments demonstrated that mice treated with 15mg/kg EC showed reduced latency to remove adhesive tape at 1d compared to vehicle controls (n=12, p<0.01). Similarly, immunoreactivity for the microglia/macrophage marker Iba1 was increased in the ipsilateral hemispheres of mice 7d after treatment with vehicle (p<0.01), whereas pretreatment with 15mg/kg blocked this effect (n=4). Mice treated with 15mg/kg also showed a trend toward reduced infarct volume relative to vehicle controls (n=5-9 per group). In subsequent reduced dosing studies, vehicle-treated mice again showed deficiencies in removing adhesive tape at 1d (n=8, p<0.01). Remarkably, mice treated with 15, 10 or 5mg/kg EC showed no deficits. Similarly, vehicle control mice showed grip strength impairments up to 7d (n=8, p<0.05) that were absent in all groups of EC-treated mice. Conclusions: Preventative administration of EC promotes functional recovery in mice subjected to experimental stroke. Investigations are underway to determine the pathways mediated by EC following administration at these therapeutic doses. Together, these data will provide insights into the potential for (-)-epicatechin as a clinical therapeutic.

scholarly journals Treatment Effects of Ischemic Stroke by Berberine, Baicalin, and Jasminoidin from Huang-Lian-Jie-Du-Decoction (HLJDD) Explored by an Integrated Metabolomics Approach

2017 ◽  
Vol 2017 ◽  
pp. 1-20 ◽  
Author(s):  
Qian Zhang ◽  
Xiaowei Fu ◽  
Junsong Wang ◽  
Minghua Yang ◽  
Lingyi Kong
Keyword(s):  
Ischemic Stroke ◽  
Treatment Effects ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
H Nmr ◽  
Abnormal Metabolism ◽  
Cerebral Artery Occlusion ◽  
First Time ◽  
Integrated Metabolomics

Berberine, baicalin, and jasminoidin were major active ingredients of Huang-Lian-Jie-Du-Decoction (HLJDD), a famous prescription of traditional Chinese medicine (TCM), which has been used for the treatment of ischemic stroke. The aim of the present study was to classify their roles in the treatment effects of ischemic stroke. A rat model of middle cerebral artery occlusion (MCAO) was constructed to mimic ischemic stroke and treatment effects of berberine, baicalin, and jasminoidin, and HLJDD was assessed by neurologic deficit scoring, infarct volume, histopathology, immunohistochemistry, biochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. In addition, the 1H NMR metabolomics approach was used to assess the metabolic profiles, which combined with correlation network analysis successfully revealed metabolic disorders in ischemic stroke concerning the treatment of the three principal compounds from HLJDD for the first time. The combined results suggested that berberine, baicalin, and jasminoidin are responsible for the effectiveness of HLJDD on the treatment of ischemic stroke by amelioration of abnormal metabolism and regulation of oxidative stress, neuron autophagy, and inflammatory response. This integrated metabolomics approach showed its potential in understanding the function of complex formulae and clarifying the role of its components in the overall treatment effects.

scholarly journals Reduction of Infarct Volume by Magnesium after Middle Cerebral Artery Occlusion in Rats

1991 ◽  
Vol 11 (6) ◽  
pp. 1025-1030 ◽  
Author(s):  
Yoshio Izumi ◽  
Simon Roussel ◽  
Elisabeth Pinard ◽  
Jacques Seylaz
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Triphenyltetrazolium Chloride ◽  
Ischemic Brain ◽  
Mca Occlusion ◽  
Cerebral Artery Occlusion ◽  
Hyperglycemic Effect

The effects of magnesium, an endogenous inhibitor of calcium entry into neurons, upon ischemic brain damage were investigated using a well-characterized model of focal cerebral ischemia in rats. Infarct volumes were determined by 2,3,5-triphenyltetrazolium chloride transcardiac perfusion 48 h after middle cerebral artery (MCA) occlusion. The area of ischemic damage was quantified by image analysis in coronal sections taken every 0.5 mm. MgCl2 (1 mmol/kg) was injected intraperitoneally just after MCA occlusion and again 1 h later. Posttreatment with MgCl2 (16 control and 16 treated rats) significantly reduced the cortical infarct volume. Compensation for the hyperglycemic effect of MgCl2 with insulin (17 rats) further reduced the infarct volume in the neocortex. No systemic effects of either treatment could account for the observed neuroprotection.

scholarly journals Hyperglycemia Accelerates Apparent Diffusion Coefficient-Defined Lesion Growth after Focal Cerebral Ischemia in Rats with and Without Features of Metabolic Syndrome

2013 ◽  
Vol 33 (10) ◽  
pp. 1556-1563 ◽  
Author(s):  
David Tarr ◽  
Delyth Graham ◽  
Lisa A Roy ◽  
William M Holmes ◽  
Christopher McCabe ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Diffusion Coefficient ◽  
Apparent Diffusion Coefficient ◽  
Middle Cerebral Artery ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Ischemic Damage ◽  
Apparent Diffusion ◽  
Cerebral Artery Occlusion

Poststroke hyperglycemia is associated with a poor outcome yet clinical management is inadequately informed. We sought to determine whether clinically relevant levels of hyperglycemia exert detrimental effects on the early evolution of focal ischemic brain damage, as determined by magnetic resonance imaging, in normal rats and in those modeling the ‘metabolic syndrome’. Wistar Kyoto (WKY) or fructose-fed spontaneously hypertensive stroke-prone (ffSHRSP) rats were randomly allocated to groups for glucose or vehicle administration before permanent middle cerebral artery occlusion. Diffusion-weighted imaging was carried out over the first 4 hours after middle cerebral artery occlusion and lesion volume calculated from apparent diffusion coefficient maps. Infarct volume and immunostaining for markers of oxidative stress were measured in the fixed brain sections at 24 hours. Hyperglycemia rapidly exacerbated early ischemic damage in both WKY and ffSHRSP rats but increased infarct volume only in WKY rats. There was only limited evidence of oxidative stress in hyperglycemic animals. Acute hyperglycemia, at clinically relevant levels, exacerbates early ischemic damage in both normal and metabolic syndrome rats. Management of hyperglycemia may have greatest benefit when performed in the acute phase after stroke in the absence or presence of comorbidities.

scholarly journals CD28 Superagonist-Mediated Boost of Regulatory T Cells Increases Thrombo-Inflammation and Ischemic Neurodegeneration during the Acute Phase of Experimental Stroke

2014 ◽  
Vol 35 (1) ◽  
pp. 6-10 ◽  
Author(s):  
Michael K Schuhmann ◽  
Peter Kraft ◽  
Guido Stoll ◽  
Kristina Lorenz ◽  
Sven G Meuth ◽  
...  
Keyword(s):  
T Cells ◽  
Ischemic Stroke ◽  
Regulatory T Cells ◽  
Thrombus Formation ◽  
Inflammatory Lesion ◽  
Artery Occlusion ◽  
Acute Stage ◽  
Experimental Stroke ◽  
Cerebral Artery Occlusion

While the detrimental role of non-regulatory T cells in ischemic stroke is meanwhile unequivocally recognized, there are controversies about the properties of regulatory T cells (Treg). The aim of this study was to elucidate the role of Treg by applying superagonistic anti-CD28 antibody expansion of Treg. Stroke outcome, thrombus formation, and brain-infiltrating cells were determined on day 1 after transient middle cerebral artery occlusion. Antibody-mediated expansion of Treg enhanced stroke size and worsened functional outcome. Mechanistically, Treg increased thrombus formation in the cerebral microvasculature. These findings confirm that Treg promote thrombo-inflammatory lesion growth during the acute stage of ischemic stroke.

Abstract WP160: Conivaptan (Combined Vasopressin Receptor Antagonism) Attenuates Cerebral Edema Following Ischemic Stroke in Rodent Model

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Saeed Ansari ◽  
Vishnumurthy Shushrutha Hedna ◽  
Sarah Ganji ◽  
Alireza Sadighi ◽  
Rashi Krishnan ◽  
...  
Keyword(s):  
Cerebral Edema ◽  
Neurological Deficit ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Neurological Deficits ◽  
Experimental Stroke ◽  
Vasopressin Receptor ◽  
Receptor Antagonism ◽  
Protein Levels

Objective: To study the potential role of Conivaptan on cerebral edema, infarct volume, neurological deficit and survival. Introduction: Although vasopressin has a significant detrimental role in stroke-related cerebral edema, the effect of mixed vasopressin antagonism in stroke has not been well studied. We studied the effects of conivaptan on the course of cerebral edema, severity of neurological deficit, infarct volume, aquaporin-4 (AQP4) protein levels and survival after experimental stroke. Methods: Animals were randomized to receive either conivaptan or vehicle after reperfusion of experimental middle cerebral artery occlusion. The severity of neurological deficit, edema, and infarct volume assessments were performed by an investigator blinded to group assignment. All assessments were performed at either 12h or 24h and Western blot was subsequently used to investigate AQP4 levels. Results: At 12h, conivaptan-treated mice (n=16) had 6.64±6.50% ipsilateral hemispheric enlargement compared to 16.55±7.05% in control mice (n=16, p=0.0003). Similarly, at 24h, conivaptan-treated mice (n=12) had 6.81±4.63% ipsilateral hemispheric enlargement in comparison to 13.93±5.43% in control mice (n=12, p=0.0023). At 24h, the conivaptan-treated mice had lower neurological deficits in comparison to control (p=0.04). There was no significant effect of conivaptan on infarct size or AQP4 levels in comparison to vehicle, naïve and sham group. Conclusions: The present study highlights the role of mixed vasopressin receptor antagonism in reducing cerebral edema secondary to brain ischemia. This data suggests the possibility of developing vasopressin antagonism as a new adjuvant in treatment of stroke-related brain edema.

scholarly journals Sex Differences in Minocycline-Induced Neuroprotection after Experimental Stroke

2009 ◽  
Vol 29 (4) ◽  
pp. 670-674 ◽  
Author(s):  
Jun Li ◽  
Louise D McCullough
Keyword(s):  
Clinical Trials ◽  
Sex Differences ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Artery Occlusion ◽  
Experimental Stroke ◽  
Ischemic Damage ◽  
Neuroprotective Agents ◽  
Stroke Patients ◽  
Cerebral Artery Occlusion

Minocycline is neuroprotective in clinical and experimental stroke studies, due in part to its ability to inhibit poly (ADP-ribose) polymerase. Previous preclinical data have shown that interference with poly (ADP-ribose) polymerase signaling leads to sex-specific neuroprotection, reducing stroke injury only in males. In this study, we show that minocycline is ineffective at reducing ischemic damage in females after middle cerebral artery occlusion, likely due to effects on poly (ADP-ribose) polymerase signaling. Clinical trials must consider possible sex differences in the response to neuroprotective agents, if we hope to translate promising therapies to stroke patients of both sexes.

scholarly journals Delayed Triphenyltetrazolium Chloride Staining Remains Useful for Evaluating Cerebral Infarct Volume in a Rat Stroke Model

1997 ◽  
Vol 17 (10) ◽  
pp. 1132-1135 ◽  
Author(s):  
Fuhai Li ◽  
Katsumi Irie ◽  
M. Sawkat Anwer ◽  
Marc Fisher
Keyword(s):  
Succinate Dehydrogenase ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Stroke Model ◽  
Sprague Dawley ◽  
Triphenyltetrazolium Chloride ◽  
Significant Difference ◽  
Cerebral Artery Occlusion ◽  
Infarcted Tissue ◽  
Time Point

Sixteen of 24 Sprague-Dawley rats with permanent middle cerebral artery occlusion for 24 hours were subjected to immediate or 8-hour delayed 2,3,5-triphenyltetrazolium chloride (TTC) staining (n = 8 at each time point); the other 8 animals were subjected to immediate or 8-hour delayed measurement of succinate dehydrogenase activity (n = 4 at each time point). The TTC staining was of good quality good in all animals, and the infarcted region could be distinguished easily from normal tissue. There was no significant difference in corrected infarct volume between the two groups (263.8 ± 43.1 versus 264.4 ± 54.8 mm3 [mean ± standard deviation]). The activity of succinate dehydrogenase was not significantly different when normal or infarcted tissue was measured immediately after death or with an 8 hour delay, although less activity was detected at both time points in the infarcted tissue. These results demonstrate that an 8-hour delay of TTC staining is reliable for evaluating brain infarct volume in a rat stroke model and this probably is attributable to the slow deterioration of mitochondrial enzyme activity in nonischemic brain over this time period.

Abstract 176: Platelet Cyclophilin D Mediates Neutrophil Recruitment and Ischemic Stroke Outcomes in Mice

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Frederik Denorme ◽  
Bhanukanth Manne ◽  
Yasuhiro Kosaka ◽  
Jennifer Majersik ◽  
Benjamin Kile ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Infarct Size ◽  
Infarct Volume ◽  
Human Platelets ◽  
Artery Occlusion ◽  
Cyclophilin D ◽  
Stroke Outcomes ◽  
Fold Reduction ◽  
Cerebral Artery Occlusion

Rationale: Besides their role in thrombosis, platelets also mediate inflammation through platelet-neutrophil aggregates (PNA). Recently, cyclophilin D (CypD)-mediated platelet necrosis emerged as a potential mediator of detrimental PNA during thrombosis. However, the role of platelet CypD in ischemic stroke has never been examined. Objective: Here, we investigate the contribution of platelet CypD following ischemic stroke. Methods: We generated mice lacking CypD specifically in platelets (KO). Both wild-type (WT) and KO mice were subjected to a 1h transient middle cerebral artery occlusion (tMCAO) stroke model. Twenty-four hours after occlusion, neurological and motor function, and stroke infarct size were determined. We also examined if the CypD pathway was altered in human platelets after ischemic stroke. Results: Loss of platelet CypD significantly improved neurological (p<0.001) and motor (p<0.005) functions compared to WT mice after tMCAO. Furthermore, platelet CypD deficient significantly reduced ischemic stroke infarct volume (39.1±15.7mm 3 vs. 78.6±27.7mm 3 , n=15; p<0.0001). Smaller infarcts in KO mice was not due to difference in blood flow during the ischemia stage. Twenty-four hours after stroke, a greater than 2-fold reduction in neutrophils was observed in the brains from KO mice (p<0.0001). In addition, we observed significantly fewer circulating and cerebral PNA (p<0.01). Depletion of neutrophils significantly (p<0.05) reduced infarct size and neurological damage following ischemic stroke in WT mice, however, no additional protective effect was observed in KO mice, suggesting necrotic PNAs are critical during ischemic stroke. RNA-sequencing on platelets isolated from ischemic stroke patients (n=8) and healthy aged, gender matched controls (n=7) revealed significant increases in several targets involved in CypD-mediated necrosis, including MCUR1, TMEM16F and calpain2 (p<0.005). Conclusion: Our results demonstrate necrotic platelets interact with neutrophils to exacerbate brain injury following ischemic stroke. As inhibiting platelet necrosis does not compromise hemostasis, targeting platelet CypD may be a potential therapeutic strategy to limit brain damage after ischemic stroke.

scholarly journals Overexpression of HSP72 after Induction of Experimental Stroke Protects Neurons from Ischemic Damage

2001 ◽  
Vol 21 (11) ◽  
pp. 1303-1309 ◽  
Author(s):  
Benjamin Hoehn ◽  
Thomas M. Ringer ◽  
Lijun Xu ◽  
Rona G. Giffard ◽  
Robert M. Sapolsky ◽  
...  
Keyword(s):  
Herpes Simplex ◽  
Artery Occlusion ◽  
Experimental Stroke ◽  
Therapeutic Window ◽  
Clinical Implications ◽  
Ischemic Damage ◽  
Striatal Neuron ◽  
Cerebral Ischemic ◽  
Cerebral Artery Occlusion ◽  
Hsp72 Expression

The 72-kD inducible heat shock protein (HSP72) can attenuate cerebral ischemic injury when overexpressed before ischemia onset. Whether HSP72 overexpression is protective when applied after ischemia onset is not known, but would have important clinical implications. Fifty-seven rats underwent middle cerebral artery occlusion for 1 hour. Defective herpes simplex viral (HSV) vectors expressing hsp72 with lacZ as a reporter were delivered 0.5, 2, and 5 hours after ischemia onset into each striatum. Control animals received an identical vector containing only lacZ. Striatal neuron survival at 2 days was improved by 23% and 15% when HSP72 vectors were delayed 0.5 and 2 hours after ischemic onset, respectively ( P < 0.05). However, when delayed by 5 hours, HSP72 overexpression was no longer protective. This is the first demonstration that HSP72 gene transfer even after ischemia onset is neuroprotective. Because expression from these HSV vectors begins 4 to 6 hours after injection, this suggests that the temporal therapeutic window for HSP72 is at least 6 hours after ischemia onset. Future strategies aimed at enhancing HSP72 expression after clinical stroke may be worth pursuing. The authors suggest that in the future HSP72 may be an effective treatment for stroke.

Sign in / Sign up

Export Citation Format

Share Document