scholarly journals Beneficial effects of mood stabilizers lithium, valproate and lamotrigine in experimental stroke models

2011 ◽  
Vol 32 (12) ◽  
pp. 1433-1445 ◽  
Author(s):  
Zhi-fei Wang ◽  
Emily Bame Fessler ◽  
De-Maw Chuang
Keyword(s):  
Mood Stabilizers ◽  
Experimental Stroke ◽  
Beneficial Effects ◽  
Stroke Models

scholarly journals Regulatory T Cell in Stroke: A New Paradigm for Immune Regulation

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Sheng Chen ◽  
Haijian Wu ◽  
Damon Klebe ◽  
Yuan Hong ◽  
Jianmin Zhang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Experimental Stroke ◽  
Central Nervous System Diseases ◽  
New Paradigm ◽  
Stroke Patients ◽  
Neuroprotective Effects ◽  
Beneficial Effects ◽  
Stroke Models ◽  
Functional Modulation ◽  
Antigen Presenting

Stroke is a common, debilitating trauma that has an incompletely elucidated pathophysiology and lacks an effective therapy. FoxP3+CD25+CD4+regulatory T cells (Tregs) suppress a variety of normal physiological and pathological immune responses via several pathways, such as inhibitory cytokine secretion, direct cytolysis induction, and antigen-presenting cell functional modulation. FoxP3+CD25+CD4+Tregs are involved in a variety of central nervous system diseases and injuries, including axonal injury, neurodegenerative diseases, and stroke. Specifically, FoxP3+CD25+CD4+Tregs exert neuroprotective effects in acute experimental stroke models. These beneficial effects, however, are difficult to elucidate. In this review, we summarized evidence of FoxP3+CD25+CD4+Tregs as potentially important immunomodulators in stroke pathogenesis and highlight further investigations for possible immunotherapeutic strategies by modulating the quantity and/or functional effects of FoxP3+CD25+CD4+Tregs in stroke patients.

scholarly journals Assessing Post-Stroke Behavior in Mouse Models of Focal Ischemia

2012 ◽  
Vol 33 (3) ◽  
pp. 330-338 ◽  
Author(s):  
Mustafa Balkaya ◽  
Jan M Kröber ◽  
Andre Rex ◽  
Matthias Endres
Keyword(s):  
Animal Studies ◽  
Treatment Strategies ◽  
Experimental Treatment ◽  
Research Process ◽  
Focal Ischemia ◽  
Poor Quality ◽  
Experimental Stroke ◽  
Behavioral Testing ◽  
Beneficial Effects ◽  
Stroke Models

Experimental treatment strategies and neuroprotective drugs that showed therapeutic promise in animal models of stroke have failed to produce beneficial effects in human stroke patients. The difficulty in translating preclinical findings to humans represents a major challenge in cerebrovascular research. The reasons behind this translational road block might be explained by a number of factors, including poor quality control in various stages of the research process, the validity of experimental stroke models, and differences in drug administration and pharmacokinetics. Another major difference between animal studies and clinical trials is the choice of end point or outcome measures. Here, we discuss the necessity of poststroke behavioral testing to bridge the gap between clinical and experimental end points. We review established sensory-motor tests for outcome determination after focal ischemia based on the published literature as well as our own personal experience. Selected tests are described in more detail and good laboratory practice standards for behavioral testing are discussed. This review is intended for stroke researchers planning to use behavioral testing in mice.

Augmentation Strategies for Clozapine-Resistant Patients with Schizophrenia

2020 ◽  
Vol 26 (2) ◽  
pp. 218-227
Author(s):  
Yi-Hang Chiu ◽  
Chia-Yueh Hsu ◽  
Mong-Liang Lu ◽  
Chun-Hsin Chen
Keyword(s):  
Sample Size ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Mood Stabilizers ◽  
Treatment Resistant ◽  
Double Blind ◽  
Beneficial Effects ◽  
Augmentation Strategies ◽  
Pubmed Database ◽  
Augmentation Strategy ◽  
Larger Sample

Background: Clozapine has been used in treatment-resistant patients with schizophrenia. However, only 40% of patients with treatment-resistant schizophrenia have response to clozapine. Many augmentation strategies have been proposed to treat those clozapine-resistant patients, but the results are inconclusive. In this review, we intended to review papers dealing with the augmentation strategies in the treatment of clozapineresistant patients with schizophrenia. Method: We reviewed randomized, double-blind, placebo- or sham-controlled trials (RCT) for clozapine-resistant patients with schizophrenia in Embase, PsycINFO, Cochrane, and PubMed database from January 1990 to June 2019. Results: Antipsychotics, antidepressants, mood stabilizers, brain stimulation, such as electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation, and other strategies, were used as an augmentation in clozapine-resistant patients with schizophrenia. Except for better evidence in memantine with 2 RCTs and cognitive behavior therapy in 2 studies to support its effectiveness, we found that all the other effective augmentations, including sulpiride, ziprasidone, duloxetine, mirtazapine, ECT, sodium benzoate, ginkgo biloba, and minocycline, had only one RCT with limited sample size. Conclusion: In this review, no definite effective augmentation strategy was found for clozapine-resistant patients. Some potential strategies with beneficial effects on psychopathology need further studies with a larger sample size to support their efficacy.

Abstract WP281: Incorporating Biological Variability in Experimental Stroke to Better Mimic Human Stroke

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Thomas A Kent ◽  
Harriett C Rea ◽  
William Dalmeida ◽  
Roderic H Fabian ◽  
Cenk Ayata ◽  
...  
Keyword(s):  
Middle Surface ◽  
Lower Surface ◽  
Clinical Results ◽  
Experimental Stroke ◽  
Biological Variability ◽  
Occlusion Time ◽  
Physiological Variability ◽  
Functional Measure ◽  
Stroke Models ◽  
Human Stroke

Introduction: Failures to translate pre-clinical results have been discouraging. We have contended that stroke is too heterogeneous with respect to factors influencing outcome to expect small studies to be balanced. It is not only difficult to control for biological and methodological variability but efforts to improve homogeneity, such as minimizing physiological variability, may render results less applicable to humans. Here, we report a predictive outcome model in experimental stroke which incorporates baseline variability and provides statistical thresholds a treatment must exceed to be efficacious in a broad population. Methods: We generated a mathematical model to predict outcome using transient MCA occlusion in 23 unfasted rats. To create baseline variability, we varied occlusion times from 90-120 min, altered baseline glucose with streptozotocin, and assessed neurological outcome 3 days later with a modified Bederson Score (BS; 0-6 functional measure, 7 death). Statistical surfaces in 3 dimensions were generated using Jacobian matrices flanking the model to provide a screening threshold (1 SD) for comparing new therapies against this model. Results: We successfully generated an outcome model from occlusion time, glucose and BS (Fig; R 2 =.49, p=.0003; middle surface is the model surrounded by ±SD surfaces). Outcome was sensitive to change in glucose and time, suggesting small imbalances in these factors between groups may influence outcome, and hence the perceived efficacy of a new therapeutic intervention. At normoglycemia and 90 mins, the lower surface overlapped with no deficit, indicating it would be difficult to reliably demonstrate benefit under those conditions. Conclusions: These results indicate it is feasible to incorporate biological variability to generate more clinically relevant conditions. The method will be tested with other stroke models and modifiers towards a generalized model to screen for therapies worthy of further study.

Do Mood Stabilizers Help in Borderline Personality Disorder?

2017 ◽  
Vol 41 (S1) ◽  
pp. S47-S47
Author(s):  
B. Völlm ◽  
J. Stoffers-Winterling ◽  
J. Mattivi ◽  
E. Simonson ◽  
O.J. Storebø ◽  
...  
Keyword(s):  
Borderline Personality Disorder ◽  
Personality Disorder ◽  
Meta Analysis ◽  
Cochrane Review ◽  
Evidence Base ◽  
Borderline Personality ◽  
Mood Stabilizers ◽  
Beneficial Effects ◽  
Drug Classes ◽  
Competing Interest

BackgroundDespite the relatively weak evidence base, individuals with borderline personality disorder are often treated with pharmacological interventions. Amongst the drugs, which have shown most promise, are mood stabilizers, which were one of the two drug classes with the most beneficial effects in a previous cochrane review though the robustness of findings was described as low (Stoffers et al., 2010). Here we present data on the latest evidence for mood stabilizers based on an updated cochrane review currently underway.MethodsA systematic review and meta-analysis of randomized controlled trials was conducted. All randomized comparisons of drug vs. placebo, drug vs. drug, or drug vs. a combination of drugs in adult BPD patients were eligible for inclusion. Outcomes comprised BPD core pathology as depicted by DSM criteria, associated pathology, i.e., depression and anxiety, general measures of overall psychopathology severity, tolerability, and adverse effects. Two researchers selected trials, assessed quality and extracted data independently.ResultsOnly a limited number of additional trials using mood stabilizers was identified since the publication of the last cochrane review, mainly utilizing Sodium Valproate. This added to the evidence base for mood stabilizers though the overall evidence remains very limited.ConclusionMood stabilizers show some initial evidence for their effectiveness in borderline personality disorder. However, these have to be replicated before wider conclusions can be drawn for clinical practice.Disclosure of interestThe authors declare that they have no competing interest.

scholarly journals Cyclophilin C-Associated Protein and Cyclophilin C mRNA are Upregulated in Penumbral Neurons and Microglia after Focal Cerebral Ischemia

2005 ◽  
Vol 25 (3) ◽  
pp. 325-337 ◽  
Author(s):  
Tatsuya Shimizu ◽  
Hideaki Imai ◽  
Koji Seki ◽  
Shinichiro Tomizawa ◽  
Mitsunobu Nakamura ◽  
...  
Keyword(s):  
Focal Cerebral Ischemia ◽  
Fold Increase ◽  
Northern Blotting ◽  
Experimental Stroke ◽  
Normal Brain ◽  
Proinflammatory Response ◽  
Neuroprotective Effects ◽  
Mca Occlusion ◽  
Stroke Models ◽  
Ischemic Core

Immunophilin ligands, such as cyclosporin A and FK506, have neuroprotective effects in experimental stroke models, although the precise mechanism is unclear. Cyclophilin C-associated protein (CyCAP) is a natural cellular ligand for the immunophilin, cyclophilin C, and has a protective effect against endotoxins by downmodulating the proinflammatory response. Expressions of CyCAP and cyclophilin C mRNA in a rat middle cerebral artery (MCA) occlusion ischemia model were investigated by Northern blotting and in situ hybridization. Both CyCAP and cyclophilin C mRNAs were ubiquitously distributed in the neurons of the normal brain. Expression increased in neurons of the periinfarct zone up to 7 days after MCA occlusion. The neuronal distribution was confirmed by counterimmunostaining of NeuN. Both mRNAs were predominantly expressed in microglia of the ischemic core at 7 days, confirmed by immunostaining with the microglial marker, ED1. The quantification of CyCAP and cyclophilin C mRNAs at 7 days by Northern blot analysis showed the 8.5-fold increase ( P<0.005, n=6) and 6.8-fold increase ( P<0.005, n=6), respectively, in ischemic core compared with control. The coincidence of CyCAP and cyclophilin C expression in neurons and microglia suggests distinct roles in each cellular population. In particular, the early increase in penumbral neurons might be related to protection in periinfarct neurons.

scholarly journals Effects of Combined Oral Conjugated Estrogens and Medroxyprogesterone Acetate on Brain Infarction Size after Experimental Stroke in Rat

2005 ◽  
Vol 25 (4) ◽  
pp. 421-426 ◽  
Author(s):  
Marguerite T Littleton-Kearney ◽  
Judy A Klaus ◽  
Patricia D Hurn
Keyword(s):  
Brain Infarction ◽  
Brain Regions ◽  
Interactive Effects ◽  
Ovariectomized Rats ◽  
Experimental Stroke ◽  
Beneficial Effects ◽  
Infarction Volume ◽  
Conjugated Equine Estrogens ◽  
Subcortical Regions ◽  
Equine Estrogens

The reason that estrogen is strongly protective in various estrogen-deficient animal models while seemingly detrimental in postmenopausal women remains unclear. It hypothesized that prolonged oral medroxyprogesterone (MPA) plus oral conjugated equine estrogens (CEE) diminishes estrogen ability to reduce stroke damage in the rodent stroke model. To test the hypothesis, we fed ovariectomized rats CEE or MPA, or a combination of CEE and MPA (CEP), before inducing 120 min of reversible focal stroke, using the intraluminal filament model. After 22 h reperfusion, the brains were harvested and infarction volumes were quantified. Treatment with CEE alone or with CEP reduced cortical infarction volume. However, CEP failed to provide ischemic protection in subcortical regions. It was concluded that CEE alone, or with CEP, is neuroprotective in the cortex, but interactive effects between the hormones may counteract CEE beneficial effects in subcortical brain regions.

scholarly journals Inhibition of CXCL12 Signaling Attenuates the Postischemic Immune Response and Improves Functional Recovery after Stroke

2013 ◽  
Vol 33 (8) ◽  
pp. 1225-1234 ◽  
Author(s):  
Karsten Ruscher ◽  
Enida Kuric ◽  
Yawei Liu ◽  
Helene L Walter ◽  
Shohreh Issazadeh-Navikas ◽  
...  
Keyword(s):  
Functional Recovery ◽  
Brain Inflammation ◽  
Experimental Stroke ◽  
Beneficial Effects ◽  
Natural Ligand ◽  
Permanent Occlusion ◽  
Concomitant Reduction ◽  
Stromal Cell Derived Factor ◽  
Tissue Reorganization ◽  
The Impact

After stroke, brain inflammation in the ischemic hemisphere hampers brain tissue reorganization and functional recovery. Housing rats in an enriched environment (EE) dramatically improves recovery of lost neurologic functions after experimental stroke. We show here that rats housed in EE after stroke induced by permanent occlusion of the middle cerebral artery (pMCAO), showed attenuated levels of proinflammatory cytokines in the ischemic core and the surrounding peri-infarct area, including a significant reduction in the stroke-induced chemokine receptor CXCR4 and its natural ligand stromal cell-derived factor-1 (CXCL12). To mimic beneficial effects of EE, we studied the impact of inhibiting CXCL12 action on functional recovery after transient MCAO (tMCAO). Rats treated with the specific CXCL12 receptor antagonist 1-[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methyl]-1,4,8,11-tetrazacyclotetradecan (AMD3100) showed improved recovery compared with saline-treated rats after tMCAO, without a concomitant reduction in infarct size. This was accompanied by a reduction of infiltrating immune cells in the ischemic hemisphere, particularly cluster of differentiation 3-positive (CD3 +) and CD3 + /CD4 + T cells. Spleen atrophy and delayed death of splenocytes, induced by tMCAO, was prevented by AMD3100 treatment. We conclude that immoderate excessive activation of the CXCL12 pathway after stroke contributes to depression of neurologic function after stroke and that CXCR4 antagonism is beneficial for the recovery after stroke.

scholarly journals Power spectrum slope and motor function recovery after focal cerebral ischemia in the rat

2018 ◽  
Author(s):  
Susan Leemburg ◽  
Bo Gao ◽  
Ertugrul Cam ◽  
Johannes Sarnthein ◽  
Claudio L. Bassetti
Keyword(s):  
Power Spectrum ◽  
Motor Function ◽  
Focal Cerebral Ischemia ◽  
Recovery Period ◽  
Artery Occlusion ◽  
Experimental Stroke ◽  
Stroke Models ◽  
Eeg Changes ◽  
Cerebral Artery Occlusion ◽  
Spectrum Slope

AbstractEEG changes across vigilance states have been observed after ischemic stroke in patients and experimental stroke models, but their relation to functional recovery remains unclear. Here, we evaluate motor function, as measured by single pellet reaching (SPR), as well as local EEG changes in NREM, REM and wakefulness during a 30-day recovery period after middle cerebral artery occlusion (MCAO) or sham surgery in rats. Small cortical infarcts resulted in poor SPR performance and induced widespread changes in EEG spectra in the ipsilesional hemisphere in all vigilance states, without causing major changes in sleep-wake architecture. Ipsilesional 1–4 Hz power was increased after stroke, whereas power in higher frequencies was reduced, resulting in a steeper slope of the power spectrum. Multielectrode array analysis of ipsilesional M1 showed that these spectral changes were present on the microelectrode level throughout M1 and were not related to increased synchronization between electrodes. Spectrum slope was significantly correlated with post-stroke motor function.

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