scholarly journals Deficiency in Protein Kinase D Activity exacerbates post‐stroke injuries and impairs functional recovery after ischemic stroke in Mice

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Jaclyn Connelly ◽  
Xuejing Zhang ◽  
Yapeng Chao ◽  
Qiming Wang
Keyword(s):  
Ischemic Stroke ◽  
Protein Kinase ◽  
Functional Recovery ◽  
Protein Kinase D ◽  
Post Stroke

scholarly journals ЗАСТОСУВАННЯ Α-ГЛІЦЕРИЛФОСФОРИЛХОЛІНУ В СХЕМІ КОМПЛЕКСНОГО ЛІКУВАННЯ ДЛЯ ФУНКЦІОНАЛЬНОГО ВІДНОВЛЕННЯ ПІСЛЯ МОЗКОВОГО ПІВКУЛЬОВОГО ІШЕМІЧНОГО ІНСУЛЬТУ

2021 ◽  
Vol 25 (3-4) ◽  
pp. 8-13
Author(s):  
О.О. Пушко ◽  
Н.В. Литвиненко
Keyword(s):  
Ischemic Stroke ◽  
Functional Recovery ◽  
Vascular Diseases ◽  
Comprehensive Treatment ◽  
Post Stroke ◽  
Rehabilitation Programs ◽  
Comprehensive Therapy ◽  
Progressive Growth ◽  
Active Rehabilitation ◽  
Combination Of Methods

The article considers the influence of α-glycerylphosphorylcholine in the scheme of comprehensive therapy on the dynamics of functional recovery in patients with cerebral hemispheric ischemic stroke. Against the background of the progressive growth of acute cerebral infarction, the problem of timely care is relevant. Timely treatment of stroke, based on evidence-based medicine, along with early activation and rehabilitation of patients is designed to reduce mortality and subsequent disability of patients. Given that cholinergic insufficiency and structural and functional damage of neurons play an important role in the pathogenesis of post-stroke disorders, the use of medicines for their correction, in particular α-glycerylphosphorylcholine, is justified. Choline alfoscerate, a precursor of acetylcholine and phosphatidylcholine, is broken down by enzymes into choline and glycerophosphate when ingested, and the choline thus obtained is able to improve neuronal functionality in patients with neurodegenerative and vascular diseases. The study revealed a significantly better recovery of impaired motor and cognitive functions after cerebral hemispheric stroke under the influence of comprehensive therapeutic and rehabilitation measures using active rehabilitation methods in conjunction with α-glycerylphosphorylcholine. The results obtained during the study allow us to report the advantage of a combination of methods of active rehabilitation and the use of the pharmacological agent α-glycerylphosphorylcholine. The feasibility and efficacy of α-glycerylphosphorylcholine are related to its ability to reduce motor and cognitive deficits after ischemic stroke. The scheme of comprehensive treatment of patients in acute and restorative periods of cerebral hemispheric ischemic stroke with the use of α-glycerylphosphorylcholine helps to increase the effectiveness of functional recovery after an acute cerebral accident, and can be used in the use of therapeutic and rehabilitation programs for patients after cerebral hemispheric ischemic stroke to reduce the post-stroke deficit.

scholarly journals GAT3 selective substrate l-isoserine upregulates GAT3 expression and increases functional recovery after a focal ischemic stroke in mice

2017 ◽  
Vol 39 (1) ◽  
pp. 74-88 ◽  
Author(s):  
Maria EK Lie ◽  
Emma K Gowing ◽  
Nina B Johansen ◽  
Nils Ole Dalby ◽  
Louise Thiesen ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Functional Recovery ◽  
Surface Expression ◽  
Tonic Inhibition ◽  
Stroke Recovery ◽  
Gaba Uptake ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Post Stroke ◽  
Long Term Treatment

Ischemic stroke triggers an elevation in tonic GABA inhibition that impairs the ability of the brain to form new structural and functional cortical circuits required for recovery. This stroke-induced increase in tonic inhibition is caused by impaired GABA uptake via the glial GABA transporter GAT3, highlighting GAT3 as a novel target in stroke recovery. Using a photothrombotic stroke mouse model, we show that GAT3 protein levels are decreased in peri-infarct tissue from 6 h to 42 days post-stroke. Prior studies have shown that GAT substrates can increase GAT surface expression. Therefore, we aimed to assess whether the GAT3 substrate, L-isoserine, could increase post-stroke functional recovery. L-Isoserine (38 µM or 380 µM) administered directly into the infarct from day 5 to 32 post-stroke, significantly increased motor performance in the grid-walking and cylinder tasks in a concentration-dependent manner, without affecting infarct volumes. Additionally, L-isoserine induced a lasting increase in GAT3 expression in peri-infarct regions accompanied by a small decrease in GFAP expression. This study is the first to show that a GAT3 substrate can increase GAT3 expression and functional recovery after focal ischemic stroke following a delayed long-term treatment. We propose that enhancing GAT3-mediated uptake dampens tonic inhibition and promotes functional recovery after stroke.

Abstract TMP121: Gender Differences in Functional Outcomes After Acute Ischemic Stroke: The Role of White Matter Structural Integrity

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Mark Etherton ◽  
Ona Wu ◽  
Pedro Cougo ◽  
Anne-Katrin Giese ◽  
Lisa Cloonan ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Acute Ischemic Stroke ◽  
Functional Recovery ◽  
Stroke Subtype ◽  
Post Stroke ◽  
Significant Difference ◽  
Acute Infarct ◽  
Underlying Mechanisms ◽  
Microstructural Integrity

Background: Women are known to have worse post-stroke outcomes; however, the underlying mechanisms remain unclear. We evaluated sex-specific clinical and neuroimaging characteristics linked to cerebrovascular brain health in association with functional recovery after acute ischemic stroke (AIS). Methods: We reviewed 316 AIS patients with acute MRI (<48 hours from symptom onset) and modified Rankin scale score (mRS) assessed at 3-6 months post-stroke. Acute infarct volume on diffusion-weighted imaging (DWIv) and white matter hyperintensity volume (WMHv) on FLAIR sequences were determined using a validated semi-automated method. Mean diffusivity (MD) and fractional anisotropy (FA) of normal appearing white matter (NAWM) were derived from the contralesional hemisphere. Wilcoxon rank sum, Spearman correlation, and Fisher’s exact tests were used at p-value <0.05, as appropriate. Results: Women comprised 41.1% of this AIS cohort, and as compared to men, they were older (68 vs. 62.8 years, p = 0.002), had higher prevalence of atrial fibrillation (21.5% vs. 12.4%, p = 0.04), and less tobacco use (21.1% vs. 36.3%, p = 0.03). There was no statistically significant difference between men and women in admission stroke severity, TOAST stroke subtype distribution, DWIv or WMHv. However, women were significantly less likely to have a favorable outcome (mRS <2), as compared to men (53.7% vs. 68.5%, p = 0.01). Both FA (ρ -0.18, p=0.04) and MD (ρ 0.28, p=0.002) values in NAWM correlated with follow-up mRS in women, but only MD (ρ 0.26, p=0.0004) in men. Conclusion: Despite no differences in admission NIHSS, acute infarct size, WMH burden or stroke subtype, women with AIS had significantly worse post-stroke outcomes in our cohort. Our findings suggest that microstructural integrity, as assessed by NAWM diffusivity anisotropy measurements, may represent a neuroimaging correlate of worse outcomes in women. The correlation between markers of white matter microstructural integrity and long-term mRS provides insight into the underlying mechanisms of disease that may influence functional recovery after stroke.

scholarly journals Galectin-3 protects against ischemic stroke by promoting neuro-angiogenesis via apoptosis inhibition and Akt/Caspase regulation

2020 ◽  
pp. 0271678X2093113
Author(s):  
Umadevi V Wesley ◽  
Ian C Sutton ◽  
Katelin Cunningham ◽  
Jacob W Jaeger ◽  
Allan Q Phan ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Rat Brain ◽  
Functional Recovery ◽  
Neuronal Cell ◽  
Vessel Density ◽  
Angiogenic Factor ◽  
Ischemic Lesion ◽  
Post Stroke ◽  
Phosphorylated Akt ◽  
Galectin 3

Post-stroke neurological deficits and mortality are often associated with vascular disruption and neuronal apoptosis. Galectin-3 (Gal3) is a potent pro-survival and angiogenic factor. However, little is known about its protective role in the cerebral ischemia/reperfusion (I/R) injury. We have previously shown significant up-regulation of Gal3 in the post-stroke rat brain, and that blocking of Gal3 with neutralizing antibody decreases the cerebral blood vessel density. Our current study demonstrates that intracerebral local delivery of the Gal3 into rat brain at the time of reperfusion exerts neuroprotection. Ischemic lesion volume and neuronal cell death were significantly reduced as compared with the vehicle-treated MCAO rat brains. Gal3 increased vessel density and neuronal survival after I/R in rat brains. Importantly, Gal3-treated groups showed significant improvement in motor and sensory functional recovery. Gal3 increased neuronal cell viability under in vitro oxygen–glucose deprivation conditions in association with increased phosphorylated-Akt, decreased phosphorylated-ERK1/2, and reduced caspase-3 activity. Gene expression analysis showed down regulation of pro-apoptotic and inflammatory genes including Fas-ligand, and upregulation of pro-survival and pro-angiogenic genes including Bcl-2, PECAM, and occludin. These results indicate a key role for Gal3 in neuro-vascular protection and functional recovery following ischemic stroke through modulation of angiogenic and apoptotic pathways.

scholarly journals Ambroxol Upregulates Glucocerebrosidase Expression to Promote Neural Stem Cells Differentiation Into Neurons Through Wnt/β-Catenin Pathway After Ischemic Stroke

2021 ◽  
Vol 13 ◽  
Author(s):  
Hongfei Ge ◽  
Chao Zhang ◽  
Yang Yang ◽  
Weixiang Chen ◽  
Jun Zhong ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Functional Recovery ◽  
Infarct Volume ◽  
Basic Knowledge ◽  
Brain Disorders ◽  
Potential Mechanism ◽  
Stroke Patients ◽  
Stroke Treatment ◽  
Post Stroke

Ischemic stroke has been becoming one of the leading causes resulting in mortality and adult long-term disability worldwide. Post-stroke pneumonia is a common complication in patients with ischemic stroke and always associated with 1-year mortality. Though ambroxol therapy often serves as a supplementary treatment for post-stroke pneumonia in ischemic stroke patients, its effect on functional recovery and potential mechanism after ischemic stroke remain elusive. In the present study, the results indicated that administration of 70 mg/kg and 100 mg/kg enhanced functional recovery by virtue of decreasing infarct volume. The potential mechanism, to some extent, was due to promoting NSCs differentiation into neurons and interfering NSCs differentiation into astrocytes through increasing GCase expression to activate Wnt/β-catenin signaling pathway in penumbra after ischemic stroke, which advanced basic knowledge of ambroxol in regulating NSCs differentiation and provided a feasible therapy for ischemic stroke treatment, even in other brain disorders in clinic.

Abstract 43: Neuroprotective Effects of Inhibition of α5β1 Integrin Following Experimental Stroke: A Dual Center Pre-Clinical Study

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Danielle Edwards ◽  
Biav Reber Kittani ◽  
Gillian Grohs ◽  
Mhairi Macrae ◽  
Justin F Fraser ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Functional Recovery ◽  
Infarct Volume ◽  
Experimental Stroke ◽  
Β1 Integrin ◽  
Integrin Receptor ◽  
Post Stroke ◽  
Enhanced Mri ◽  
Bbb Permeability ◽  
Α5β1 Integrin

Blood-brain barrier (BBB) dysfunction after ischemic stroke exacerbates brain damage by contributing to edema and inflammation. The β1 integrin receptor family may contribute to this dysfunction via alteration of BBB-forming tight junction proteins. We hypothesize that inhibition of the β1 integrin receptor subtype α5β1, which is acutely expressed in infarct and peri-infarct vasculature after experimental stroke, reduces BBB permeability, reduces infarct volume, and improves functional recovery. A randomized and blinded trial was conducted using transient middle cerebral artery occlusion (MCAO) in mice (60 min; n=8) and rats (90 min; n=15) in two independent laboratories. ATN-161 (α5β1 inhibitor; 1 mg/kg) was administered IV immediately upon reperfusion and on post-stroke day 1 and 2. Infarct volume was determined by cresyl violet (mice) and T 2 weighted MRI (rat) at day 3 post MCAO. Steady state contrast enhanced MRI was used to assess BBB breakdown in rats at day 3. ATN-161 resulted in a significant reduction in infarct volume in both mice and rats when measured at post-stroke day 3 (p<0.001). BBB permeability was decreased upon ATN-161 treatment in vivo as determined by reduced IgG and claudin-5 immunostaining in mice and reduced extent of Gadolinium enhanced MRI signal change in rats. Behavioral tests (open field, rotorod, sticky label and 28 point neuroscore), demonstrated significantly improved functional recovery in both mice and rats following treatment with ATN-161. Finally, in vitro studies where stroke was simulated using oxygen and glucose deprivation or TNF-α, ATN-161 (10 μM) treatment demonstrated decreased barrier permeability as measured by trans-endothelial cell electrical resistance, FITC-dextran permeability, and claudin-5 immunocytochemistry. Collectively, our results demonstrate that post-stroke inhibition of α5β1 integrin with the small peptide ATN-161 profoundly reduces infarct volume, improves functional outcome and decreases BBB permeability in both mice and rats using two different ischemic stroke models. Therefore, inhibition of α5β1 by ATN-161 could represent a novel stroke therapeutic target worthy of further investigation.

scholarly journals Association Between Levels of Serum Insulin-like Growth Factor I and Functional Recovery, Mortality, and Recurrent Stroke at a 7-year Follow-up

2019 ◽  
Vol 128 (05) ◽  
pp. 303-310 ◽  
Author(s):  
N. David Åberg ◽  
Daniel Åberg ◽  
Cecilia Lagging ◽  
Lukas Holmegaard ◽  
Petra Redfors ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Growth Factor ◽  
Functional Recovery ◽  
Recurrent Stroke ◽  
Serum Insulin ◽  
Insulin Like Growth Factor ◽  
Post Stroke ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I

Abstract Background The association of serum insulin-like growth factor I (s-IGF-I) with favorable outcome after ischemic stroke (IS) beyond 2 years is unknown. We investigated whether the levels of s-IGF-I 3 months post-stroke were associated with functional recovery up to 7 years after IS, considering also mortality and recurrent strokes. Methods Patients (N=324; 65% males; mean age, 55 years) with s-IGF-I levels assessed 3 months after the index IS were included from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). The modified Rankin Scale (mRS) was used to evaluate outcomes at 3 months, 2 and 7 years after IS, and recovery was defined as an improvement, no change, or deterioration in the shifts of mRS score. Baseline stroke severity was determined using the National Institutes of Health Stroke Scale (NIHSS). Results The mRS score distributions were better in the above-median s-IGF-I group (>146.7 ng/ml). The s-IGF-I level was not associated with recurrent stroke (N=79) or death (N=44), although it correlated with recovery (r=0.12, P=0.035). In the regression analysis, s-IGF-I associated with recovery between 3 months and 7 years (but not between 2 and 7 years). The associations did not withstand adjustment for age and sex. For comparison, the corresponding associations between 3 months and 2 years withstood all adjustments. Conclusion The association for s-IGF-I with long-term post-stroke recovery persists after 7 years, which is also reflected in the mRS score distributions at all time-points. The effects are however modest, and not driven by mortality or recurrent stroke.

Abstract WP105: An Effective Delayed Treatment for Ischemic Stroke Uses Fluoxetine and Simvastatin

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Adrian Corbett ◽  
Scott Sieber ◽  
Nicholas Wyatt ◽  
Jenna Lizzi ◽  
Tiffany Flannery ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Ischemic Stroke ◽  
Drug Treatment ◽  
Functional Recovery ◽  
Adult Neurogenesis ◽  
Fold Increase ◽  
Vehicle Control ◽  
Combination Drug ◽  
Stroke Treatment ◽  
Post Stroke

For more than 90% of ischemic stroke patients there exists no standardized drug treatment other than giving aspirin or beginning statin treatment for the prevention of future strokes. The purpose of this study was to develop a delayed pharmacological treatment for ischemic stroke, utilizing a combination of drugs that would enhance adult neurogenesis and brain-derived neurotrophic factor. An endothelin-induced stroke was produced in 10-12 month old rats, which have previously been trained on Montoya Staircase and Forelimb Asymmetry tests. Combination drug treatments were tested against vehicle controls, beginning 20-26 hours after stroke induction and continuing for 31 days. Functional tests were performed at various times post-stroke. Daily treatments of 5 mg/kg fluoxetine in combination with 0.5 mg/kg simvastatin and 20 mg/kg ascorbic acid produced a 19-fold increase in neurogenesis (P=0.001 compared to vehicle control), while fluoxetine alone produced a 10-fold increase in neurogenesis (P=0.007 compared to vehicle control). This combination drug treatment results in almost complete functional recovery as measured by Montoya Staircase (mean recovery to 85% of pre-stroke function, P=0.023) and Forelimb Asymmetry tests (mean recovery to 90% of pre-stroke function, P=0.041 and P= 0.05) in 10-12 month old stroked female Long Evans rats. Additional testing of 5 mg/kg fluoxetine and 20 mg/kg ascorbic acid drug combination as a delayed post-stroke treatment has only given half of the functional recovery seen when all three drugs are included, indicating that the statin is essential for full recovery. Fluoxetine is likely to be the other essential component of this combination treatment as it alone resulted in a significant increase in adult neurogenesis.

Abstract 19: Resolving Post-Stroke Depression is associated with Post-Stroke Functional Recovery

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Nada El Husseini ◽  
Larry B Goldstein ◽  
Eric D Peterson ◽  
Xin Zhao ◽  
Wenqin Pan ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Functional Outcome ◽  
Functional Recovery ◽  
The United States ◽  
Reciprocal Relationship ◽  
Older Age ◽  
Post Stroke ◽  
Depression Status ◽  
Post Stroke Depression ◽  
Time Point

Background/rationale: Depression is common after stroke and is associated with poor functional outcome, but its relationship with the change in functional status after adjustment for other factors remains uncertain. We investigated the independent relationship between depression and post-stroke functional recovery. Methods: Data were obtained as part of the multicenter Adherence eValuation After Ischemic stroke-Longitudinal (AVAIL) registry in which depression assessed by a self-reported depressive symptoms scale (the Patient Health Questionnaire-8; PHQ-8≥10), and modified Rankin scale (mRS) were prospectively assessed 3 and 12 months following hospitalization for ischemic stroke. Univariate logistic analysis followed by multivariable logistic modeling adjusted for race, gender, age and post-hospital rehabilitation, was performed to evaluate the association between depression at each time-point and the change in mRS between 3 and 12 months. Results: Data was available for 1444 patients (55.7% men, 82.6% White) from 97 hospitals in the United States. Relative to 3 months, the 12 month mRS was stable or improved in 692 (75.8%) and worse in 349 (24.2%) patients. Overall, 134 patients were persistently depressed, 126 had resolving depression by 12 months and 104 patients had incident depression at 12 months. Older age, lack of rehabilitation, and 3 and 12 months depression status were associated with worse disability (increasing mRS) between 3 and 12 months. After covariate adjustment, both depression status at 3 and 12 months (p= 0.010) and older age (OR= 1.02, 95% CI 1.01-1.03 per 10-years, p<0.001) remained associated with worsening mRS. Compared with those who were not depressed at either time point, those who had resolving depression (PHQ-8≥10 at 3 but not 12 months) were less likely to have a worsening mRS (OR=0.49, 95%CI 0.29-0.83) whereas the association between incident depression at 12 month and worsening mRS was marginal (OR=1.48, 95% CI 0.95-2.30). Being depressed at both time points was not associated with a worsening in mRS between 3 and 12 months (OR=0.85, 95% CI 0.53-1.34). Conclusion: The change in depressive status between 3 and 12 months following hospitalization for stroke was associated with incremental changes in functional outcome. Patients who had resolving post-stroke depression were less likely to have worsening disability. A reciprocal relationship and a confounding effect between depression and mRS cannot be excluded.

Sign in / Sign up

Export Citation Format

Share Document