Abstract TP116: Effect of Voluntary Physical Activity on Circulating LG3 and Its Impact on Ischemic Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Ifechukwude Joachim Biose ◽  
Katie E Salmeron ◽  
Anthony Parker ◽  
Ann Stowe ◽  
Gregory Bix
Keyword(s):  
Physical Activity ◽  
Ischemic Stroke ◽  
Infarct Volume ◽  
Exercise Group ◽  
Artery Occlusion ◽  
Control Group ◽  
Lesion Volume ◽  
Ischemic Lesion ◽  
Voluntary Physical Activity ◽  
Wheel Activity

Physical activity (PA) is neuroprotective. However, the mechanism for the benefit of PA prior to ischemic stroke is not well understood. Circulating LG3 levels, a 25-kDa protein fragment of brain extracellular matrix proteoglycan (perlecan), increases with PA in humans. We showed that LG3 significantly reduces infarct volume following ischemic stroke. The aim of this study is to assess whether LG3 concentration increases with voluntary physical activity in mice and to determine how circulating LG3 concentration, prior to ischemic stroke, influences outcomes. Male mice (C57BL/6J, 8-9 weeks old, 21–24 g) were randomized into sedentary control group (individually housed in motorized running wheel cages with applied brakes) and an exercise group with access to running wheels. Blood draws were collected via submental method on day 1, 7, 14 and 20 of wheel activity prior to middle cerebral artery occlusion (MCAO), to evaluate LG3 concentration in serum. Following three weeks of voluntary PA or sedentary condition, 25 mice (sedentary n=13, exercise n=12) underwent transient distal MCAO for 60 min and were recovered for three days. In another study, 29 mice (sedentary n=15, exercise n=14) underwent transient proximal MCAO for 60 min. Calf muscles (soleus and gastrocnemius) and brain samples were collected for histology, protein analysis, and infarct volume assessment. We show that voluntary PA significantly reduces ischemic lesion volume compared to sedentary controls, following distal MCAO (15.2±8 vs 5.3±2 mm 3 ; P<0.0001, Figure 1). The analysis of LG3 concentration, neurofunction, as well as brain and muscle samples are currently ongoing. We expect that the findings will link LG3 concentration to the volume of exercise as well as the neuroprotection it confers in the setting of ischemic stroke.

scholarly journals Neuroprotective mechanisms of erythropoietin in a rat stroke model

2020 ◽  
Vol 11 (1) ◽  
pp. 48-59
Author(s):  
Martin Juenemann ◽  
Tobias Braun ◽  
Nadine Schleicher ◽  
Mesut Yeniguen ◽  
Patrick Schramm ◽  
...  
Keyword(s):  
Blood Flow ◽  
Infarct Size ◽  
Cerebral Edema ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Lesion Volume ◽  
Ischemic Lesion ◽  
Human Erythropoietin ◽  
Male Wistar Rats ◽  
Cerebral Artery Occlusion

AbstractObjectiveThis study was designed to investigate the indirect neuroprotective properties of recombinant human erythropoietin (rhEPO) pretreatment in a rat model of transient middle cerebral artery occlusion (MCAO).MethodsOne hundred and ten male Wistar rats were randomly assigned to four groups receiving either 5,000 IU/kg rhEPO intravenously or saline 15 minutes prior to MCAO and bilateral craniectomy or sham craniectomy. Bilateral craniectomy aimed at elimination of the space-consuming effect of postischemic edema. Diagnostic workup included neurological examination, assessment of infarct size and cerebral edema by magnetic resonance imaging, wet–dry technique, and quantification of hemispheric and local cerebral blood flow (CBF) by flat-panel volumetric computed tomography.ResultsIn the absence of craniectomy, EPO pretreatment led to a significant reduction in infarct volume (34.83 ± 9.84% vs. 25.28 ± 7.03%; p = 0.022) and midline shift (0.114 ± 0.023 cm vs. 0.083 ± 0.027 cm; p = 0.013). We observed a significant increase in regional CBF in cortical areas of the ischemic infarct (72.29 ± 24.00% vs. 105.53 ± 33.10%; p = 0.043) but not the whole hemispheres. Infarct size-independent parameters could not demonstrate a statistically significant reduction in cerebral edema with EPO treatment.ConclusionsSingle-dose pretreatment with rhEPO 5,000 IU/kg significantly reduces ischemic lesion volume and increases local CBF in penumbral areas of ischemia 24 h after transient MCAO in rats. Data suggest indirect neuroprotection from edema and the resultant pressure-reducing and blood flow-increasing effects mediated by EPO.

scholarly journals Optogenetic Inhibition of Striatal Neuronal Activity Improves the Survival of Transplanted Neural Stem Cells and Neurological Outcomes after Ischemic Stroke in Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Yifan Lu ◽  
Lu Jiang ◽  
Wanlu Li ◽  
Meijie Qu ◽  
Yaying Song ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Neuronal Activity ◽  
Brain Ischemia ◽  
Fluorescent Protein ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Control Group ◽  
Striatal Neurons ◽  
And Migration

Neural stem cell (NSC) transplantation is a promising treatment to improve the recovery after brain ischemia. However, how the survival, proliferation, migration, and differentiation of implanted NSC are influenced by endogenous neuronal activity remains unclear. In this work, we used optogenetic techniques to control the activity of striatal neurons and investigated how their activity affected the survival and migration of transplanted NSCs and overall neurological outcome after ischemic stroke. NSCs cultured from transgenic mice expressing fluorescent protein were transplanted into the peri-infarct region of the striatum after transient middle cerebral artery occlusion (tMCAO) surgery. The striatal neurons were excited or inhibited for 15 minutes daily via implanted optical fiber after tMCAO. The results revealed that mice which received NSC transplantation and optogenetic inhibition had smaller brain infarct volume and increased NSC migration compared to the NSC alone or PBS group (p<0.05). In contrast, mice which received NSC transplantation and optogenetic excitation showed no difference in infarct volume and neurological behavior improvement compared to the PBS control group. In vitro experiments further revealed that the conditioned media from excited GABAergic neurons reduced NSC viability through paracrine mechanisms.Conclusion. Optogenetic inhibition of striatal neuronal activity further improved neurological recovery after NSC transplantation at the subacute phase after brain ischemia.

The relationship of oxidative stress parameters with infarct volume and National Institutes of Health Stroke Scale in ischemic stroke / İskemik inmede oksidatif stres parametrelerinin infarkt volümü ve National Institutes of Health Stroke Scale ile ilişkisi

2015 ◽  
Vol 40 (4) ◽  
Author(s):  
Ferhat İçme ◽  
Özcan Erel ◽  
Zeynep Saral Öztürk ◽  
Tolga Öz ◽  
Akkan Avci ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ischemic Stroke ◽  
Infarct Volume ◽  
National Institutes Of Health ◽  
Control Group ◽  
Case Group ◽  
Ischemic Lesion ◽  
Oxidative Stress Parameters ◽  
The Relationship ◽  
Stress Parameters

AbstractObjective: What we know about the relationship between oxidative stress parameters and ischemic stroke is still limited and controversial. Our study aimed to investigate the relationships among ischemic lesion volume, National Institutes of Health Stroke Scale (NIHSS) values, and oxidant and antioxidant levels to determine whether oxidative stress paramaters is effective on stroke severity in ischemic stroke patients.Methods: The study included 34 patients with ischemic stroke and 34 volunteers with no active diseases. Total Oxidant Status (TOS), Total Antioxidant Status (TAS), thiol, paraoxonase, stimulated paraoxonase (stparaoxonase) and arylesterase were measured in blood samples collected on admission from patients diagnosed with ischemic stroke. The Oxidative Stress Index (OSI) was calculated. The same oxidative stress parameters were measured in the control group and compared with the patient group. Correlation between the oxidative stress parameters, the infarct volume and the NIHSS was studied. NIHSS was calculated when patients were admitted to the emergency department. The infarct volume was calculated using diffusion-weighted magnetic resonance imaging performed in the first 72-96 hours.Results: TOS and OSI values were significantly higher in the case group than the control group. Paraoxonase, arylesterase, and thiol values were significantly lower in the case group than the control group. TAS and stparaoxonase values weren’t differed significantly between the case and control groups. There were significant negative correlations between the NIHSS value and both the paraoxonase value and stparaoxonase value. There were no significant correlations between the NIHSS value and the infarct volume and the TAS, TOS, OSI, arylesterase, and thiol values.Conclusion: We concluded that change in oxidative stress balance in favor of oxidants could be a cause in the pathogenesis of ischemic stroke but oxidative stress alone can’t be sufficient in predicting the severity of stroke.

scholarly journals Glibenclamide Administration Attenuates Infarct Volume, Hemispheric Swelling, and Functional Impairments following Permanent Focal Cerebral Ischemia in Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Bushra Wali ◽  
Tauheed Ishrat ◽  
Fahim Atif ◽  
Fang Hua ◽  
Donald G. Stein ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Grip Strength ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Constant Infusion ◽  
Lesion Volume ◽  
Functional Impairments ◽  
Sprague Dawley ◽  
Neuroprotective Effects

Studies from a single laboratory have shown that in rodent models of permanent stroke, administration of the sulfonylurea glibenclamide (Glib) is highly effective in reducing edema, mortality, and lesion volume. The Stroke Therapy Academic Industry Roundtable (STAIR) recommends that new acute treatments for ischemic stroke to be replicated across different laboratories. Accordingly, we examined the effect of low-dose Glib in a permanent suture occlusion model of stroke. Male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (pMCAO) followed by an initial intraperitoneal injection of Glib (10 μg/kg) and the start of a constant infusion (200 ng/h) via miniosmotic pump at the onset of ischemia. Functional deficits were assessed by Neurological Severity Score (NSS) and grip-strength meter at 24 and 48 h after pMCAO. Glib-treated rats showed a significant reduction in infarct volume, lower NSS, and less hemispheric swelling compared to vehicle. Grip strength was decreased significantly in pMCAO rats compared to shams and significantly improved by treatment with Glib. Taken together, these data indicate that Glib has strong neuroprotective effects following ischemic stroke and may warrant further testing in future clinical trials for human stroke.

scholarly journals Gender Differences in Outcomes after Ischemic Stroke: Role of Ischemic Lesion Volume and Intracranial Large-Artery Occlusion

2010 ◽  
Vol 30 (5) ◽  
pp. 470-475 ◽  
Author(s):  
Gisele S. Silva ◽  
Fabricio O. Lima ◽  
Erica C.S. Camargo ◽  
Wade S. Smith ◽  
Michael H. Lev ◽  
...  
Keyword(s):  
Gender Differences ◽  
Ischemic Stroke ◽  
Artery Occlusion ◽  
Lesion Volume ◽  
Large Artery ◽  
Ischemic Lesion

scholarly journals The Role of Edema in Subacute Lesion Progression After Treatment of Acute Ischemic Stroke

2021 ◽  
Vol 12 ◽  
Author(s):  
Praneeta Konduri ◽  
Katinka van Kranendonk ◽  
Anna Boers ◽  
Kilian Treurniet ◽  
Olvert Berkhemer ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Functional Outcome ◽  
Water Uptake ◽  
Infarct Volume ◽  
Lesion Volume ◽  
Ischemic Lesion ◽  
Contrast Ct ◽  
Mr Clean

Background: Ischemic lesions commonly continue to progress even days after treatment, and this lesion growth is associated with unfavorable functional outcome in acute ischemic stroke patients. The aim of this study is to elucidate the role of edema in subacute lesion progression and its influence on unfavorable functional outcome by quantifying net water uptake.Methods: We included all 187 patients from the MR CLEAN trial who had high quality follow-up non-contrast CT at 24 h and 1 week. Using a CT densitometry-based method to calculate the net water uptake, we differentiated total ischemic lesion volume (TILV) into edema volume (EV) and edema-corrected infarct volume (ecIV). We calculated these volumes at 24 h and 1 week after stroke and determined their progression in the subacute period. We assessed the effect of 24-h lesion characteristics on EV and ecIV progression. We evaluated the influence of edema and edema-corrected infarct progression on favorable functional outcome after 90 days (modified Rankin Scale: 0–2) after correcting for potential confounders. Lastly, we compared these volumes between subgroups of patients with and without successful recanalization using the Mann–Whitney U-test.Results: Median TILV increased from 37 (IQR: 18–81) ml to 68 (IQR: 30–130) ml between 24 h and 1 week after stroke, while the net water uptake increased from 22 (IQR: 16–26)% to 27 (IQR: 22–32)%. The TILV progression of 20 (8.8–40) ml was mostly caused by ecIV with a median increase of 12 (2.4–21) ml vs. 6.5 (2.7–15) ml of EV progression. Larger TILV, EV, and ecIV volumes at 24 h were all associated with more edema and lesion progression. Edema progression was associated with unfavorable functional outcome [aOR: 0.53 (0.28–0.94) per 10 ml; p-value: 0.05], while edema-corrected infarct progression showed a similar, non-significant association [aOR: 0.80 (0.62–0.99); p-value: 0.06]. Lastly, edema progression was larger in patients without successful recanalization, whereas ecIV progression was comparable between the subgroups.Conclusion: EV increases in evolving ischemic lesions in the period between 1 day and 1 week after acute ischemic stroke. This progression is larger in patients without successful recanalization and is associated with unfavorable functional outcome. However, the extent of edema cannot explain the total expansion of ischemic lesions since edema-corrected infarct progression is larger than the edema progression.

scholarly journals Selective intra-carotid blood cooling in acute ischemic stroke: A safety and feasibility study in an ovine stroke model

2021 ◽  
pp. 0271678X2110249
Author(s):  
Giorgio FM Cattaneo ◽  
Andrea M Herrmann ◽  
Sebastian A Eiden ◽  
Manuela Wieser ◽  
Elias Kellner ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Carotid Artery ◽  
Acute Ischemic Stroke ◽  
Neurological Outcome ◽  
Artery Occlusion ◽  
Control Group ◽  
Stroke Model ◽  
Primary Endpoints ◽  
Neuroprotective Strategy ◽  
Vessel Patency

Selective therapeutic hypothermia (TH) showed promising preclinical results as a neuroprotective strategy in acute ischemic stroke. We aimed to assess safety and feasibility of an intracarotid cooling catheter conceived for fast and selective brain cooling during endovascular thrombectomy in an ovine stroke model. Transient middle cerebral artery occlusion (MCAO, 3 h) was performed in 20 sheep. In the hypothermia group (n = 10), selective TH was initiated 20 minutes before recanalization, and was maintained for another 3 h. In the normothermia control group (n = 10), a standard 8 French catheter was used instead. Primary endpoints were intranasal cooling performance (feasibility) plus vessel patency assessed by digital subtraction angiography and carotid artery wall integrity (histopathology, both safety). Secondary endpoints were neurological outcome and infarct volumes. Computed tomography perfusion demonstrated MCA territory hypoperfusion during MCAO in both groups. Intranasal temperature decreased by 1.1 °C/3.1 °C after 10/60 minutes in the TH group and 0.3 °C/0.4 °C in the normothermia group (p < 0.001). Carotid artery and branching vessel patency as well as carotid wall integrity was indifferent between groups. Infarct volumes (p = 0.74) and neurological outcome (p = 0.82) were similar in both groups. Selective TH was feasible and safe. However, a larger number of subjects might be required to demonstrate efficacy.

scholarly journals Associations of Ischemic Lesion Volume With Functional Outcome in Patients With Acute Ischemic Stroke

Stroke ◽  
2017 ◽  
Vol 48 (5) ◽  
pp. 1233-1240 ◽  
Author(s):  
Amber Bucker ◽  
Anna M. Boers ◽  
Joseph C.J. Bot ◽  
Olvert A. Berkhemer ◽  
Hester F. Lingsma ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Functional Outcome ◽  
Lesion Volume ◽  
Ischemic Lesion

scholarly journals Three-dimensional cultured mesenchymal stem cells enhance repair of ischemic stroke through inhibition of microglia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yuejiao Li ◽  
Yankai Dong ◽  
Ye Ran ◽  
Yanan Zhang ◽  
Boyao Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ischemic Stroke ◽  
Proinflammatory Cytokines ◽  
Infarct Volume ◽  
Brain Lesion ◽  
Three Dimensional ◽  
Artery Occlusion ◽  
Rna Seq ◽  
The Brain

Abstract Background We show previously that three-dimensional (3D) spheroid cultured mesenchymal stem cells (MSCs) exhibit reduced cell size thus devoid of lung entrapment following intravenous (IV) infusion. In this study, we determined the therapeutic effect of 3D-cultured MSCs on ischemic stroke and investigated the mechanisms involved. Methods Rats underwent middle cerebral artery occlusion (MCAO) and reperfusion. 1 × 106 of 3D- or 2D-cultured MSCs, which were pre-labeled with GFP, were injected through the tail vain three and seven days after MCAO. Two days after infusion, MSC engraftment into the ischemic brain tissues was assessed by histological analysis for GFP-expressing cells, and infarct volume was determined by MRI. Microglia in the lesion were sorted and subjected to gene expressional analysis by RNA-seq. Results We found that infusion of 3D-cultured MSCs significantly reduced the infarct volume of the brain with increased engraftment of the cells into the ischemic tissue, compared to 2D-cultured MSCs. Accordingly, in the brain lesion of 3D MSC-treated animals, there were significantly reduced numbers of amoeboid microglia and decreased levels of proinflammatory cytokines, indicating attenuated activation of the microglia. RNA-seq of microglia derived from the lesions suggested that 3D-cultured MSCs decreased the response of microglia to the ischemic insult. Interestingly, we observed a decreased expression of mincle, a damage-associated molecular patterns (DAMPs) receptor, which induces the production of proinflammatory cytokines, suggestive of a potential mechanism in 3D MSC-mediated enhanced repair to ischemic stroke. Conclusions Our data indicate that 3D-cultured MSCs exhibit enhanced repair to ischemic stroke, probably through a suppression to ischemia-induced microglial activation.

scholarly journals Cerebral endothelial cell-derived small extracellular vesicles enhance neurovascular function and neurological recovery in rat acute ischemic stroke models of mechanical thrombectomy and embolic stroke treatment with tPA

2021 ◽  
pp. 0271678X2199298
Author(s):  
Chao Li ◽  
Chunyang Wang ◽  
Yi Zhang ◽  
Owais K Alsrouji ◽  
Alex B Chebl ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Extracellular Vesicles ◽  
Mechanical Thrombectomy ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Therapeutic Effects ◽  
Vessel Occlusion ◽  
Healthy Human ◽  
Stroke Treatment

Treatment of patients with cerebral large vessel occlusion with thrombectomy and tissue plasminogen activator (tPA) leads to incomplete reperfusion. Using rat models of embolic and transient middle cerebral artery occlusion (eMCAO and tMCAO), we investigated the effect on stroke outcomes of small extracellular vesicles (sEVs) derived from rat cerebral endothelial cells (CEC-sEVs) in combination with tPA (CEC-sEVs/tPA) as a treatment of eMCAO and tMCAO in rat. The effect of sEVs derived from clots acquired from patients who had undergone mechanical thrombectomy on healthy human CEC permeability was also evaluated. CEC-sEVs/tPA administered 4 h after eMCAO reduced infarct volume by ∼36%, increased recanalization of the occluded MCA, enhanced cerebral blood flow (CBF), and reduced blood-brain barrier (BBB) leakage. Treatment with CEC-sEVs given upon reperfusion after 2 h tMCAO significantly reduced infarct volume by ∼43%, and neurological outcomes were improved in both CEC-sEVs treated models. CEC-sEVs/tPA reduced a network of microRNAs (miRs) and proteins that mediate thrombosis, coagulation, and inflammation. Patient-clot derived sEVs increased CEC permeability, which was reduced by CEC-sEVs. CEC-sEV mediated suppression of a network of pro-thrombotic, -coagulant, and -inflammatory miRs and proteins likely contribute to therapeutic effects. Thus, CEC-sEVs have a therapeutic effect on acute ischemic stroke by reducing neurovascular damage.

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