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Post-ischemic stroke systemic inflammation: Immunomodulation by progesterone and vitamin D hormone.
In this study, we examined the immunomodulatory effects of progesterone (P4) alone and in combination with vitamin D hormone (VDH) on acute phase post-stroke peripheral immune dysfunction and functional/behavioral deficits. Adult rats underwent transient middle cerebral artery occlusion/reperfusion (tMCAO) and delayed systemic inflammation was induced by injections of lipopolysaccharide (LPS) beginning 24 h post-stroke. Animals were tested for behavioral outcomes and immune function at day 4 post-stroke. We also measured infarction volume and markers of neuronal inflammation (GFAP, IL-6) and apoptosis (cleaved caspase-3) ...
Source: Neuropharmacology - September 16, 2020 Category: Drugs & Pharmacology Authors: Atif F, Yousuf S, Espinosa-Garcia C, Harris WAC, Stein DG Tags: Neuropharmacology Source Type: research

Glucagon-like receptor 1 agonists and DPP-4 inhibitors: Anti-diabetic drugs with anti-stroke potential.
Abstract Stroke is one of the leading causes of death and serious disability in Westernized societies. The risk of stroke approximately doubles with each decade after the age of 55. Therefore, even though the incidence of stroke is declining, mostly because of the efforts to lower blood pressure and reduce smoking, the overall number of strokes is increasing due to the aging of the population. While stroke prevention by healthy lifestyle is effective in decreasing the risk of stroke, post stroke pharmacological strategies aimed at minimizing stroke-induced brain damage and promoting recovery are highly needed. Unf...
Source: Neuropharmacology - August 17, 2017 Category: Drugs & Pharmacology Authors: Darsalia V, Klein T, Nyström T, Patrone C Tags: Neuropharmacology Source Type: research

Cell-based and pharmacological neurorestorative therapies for ischemic stroke.
Abstract Ischemic stroke remains one of most common causes of death and disability worldwide. Stroke triggers a cascade of events leading to rapid neuronal damage and death. Neuroprotective agents that showed promise in preclinical experiments have failed to translate to the clinic. Even after decades of research, tPA remains the only FDA approved drug for stroke treatment. However, tPA is effective when administered 3-4.5 h after stroke onset and the vast majority of stroke patients do not receive tPA therapy. Therefore, there is a pressing need for novel therapies for ischemic stroke. Since stroke induces rapid...
Source: Neuropharmacology - August 31, 2017 Category: Drugs & Pharmacology Authors: Venkat P, Shen Y, Chopp M, Chen J Tags: Neuropharmacology Source Type: research

Animal models of ischaemic stroke and characterisation of the ischaemic penumbra.
Abstract Over the past forty years, animal models of focal cerebral ischaemia have allowed us to identify the critical cerebral blood flow thresholds responsible for irreversible cell death, electrical failure, inhibition of protein synthesis, energy depletion and thereby the lifespan of the potentially salvageable penumbra. They have allowed us to understand the intricate biochemical and molecular mechanisms within the 'ischaemic cascade' that initiate cell death in the first minutes, hours and days following stroke. Models of permanent, transient middle cerebral artery occlusion and embolic stroke have been deve...
Source: Neuropharmacology - September 16, 2017 Category: Drugs & Pharmacology Authors: McCabe C, Arroja MM, Reid E, Macrae IM Tags: Neuropharmacology Source Type: research

Title: The effect of pyruvate on the development and progression of post-stroke depression: A new therapeutic approach.
Abstract Post-stroke depression (PSD) is a common and serious complication following stroke. Both stroke and depression have independently been associated with pathologically elevated glutamate levels in the brain's extra-cerebral fluid (ECF). Here we evaluate an alternative therapeutic approach to PSD with pyruvate. Rats were randomly assigned into one of 3 groups: Middle Cerebral Artery Occlusion (MCAO) plus pyruvate treatment, MCAO plus placebo treatment, and sham operated rats. Post-MCAO depressive and anxiety-like behavior was assessed, along with neurological status, brain infarct zone, brain edema, blood br...
Source: Neuropharmacology - May 29, 2019 Category: Drugs & Pharmacology Authors: Frank D, Kuts R, Tsenter P, Gruenbaum BF, Grinshpun Y, Zvenigorodsky V, Shelef I, Natanel D, Brotfain E, Zlotnik A, Boyko M Tags: Neuropharmacology Source Type: research

First evidence of protective effects on stroke recovery and post-stroke depression induced by sortilin-derived peptides.
Abstract Post-stroke depression (PSD) is the most common mood disorder following stroke with high relevance for outcome and survival of patients. The TREK-1 channel represents a crucial target in the pathogenesis of stroke and depression. Spadin and its short analog mini-spadin were reported to display potent antidepressant properties. We investigated the therapeutic effects of mini-spadin in a mouse model of focal ischemia and PSD. To activate TREK-1 and induce neuroprotection a single low dose of mini-spadin (0.03 μg/kg) was intraperitoneally injected 30 min after the onset of ischemia, once a day during 7 ...
Source: Neuropharmacology - July 16, 2019 Category: Drugs & Pharmacology Authors: Pietri M, Djillani A, Mazella J, Borsotto M, Heurteaux C Tags: Neuropharmacology Source Type: research

Venlafaxine treatment after endothelin-1-induced cortical stroke modulates growth factor expression and reduces tissue damage in rats.
Abstract Neuromodulators, such as antidepressants, may contribute to neuroprotection by modulating growth factor expression to exert anti-inflammatory effects and to support neuronal plasticity after stroke. Our objective was to study whether early treatment with venlafaxine, a serotonin-norepinephrine reuptake inhibitor, modulates growth factor expression and positively contributes to reducing the volume of infarcted brain tissue resulting in increased functional recovery. We studied the expression of BDNF, FGF2 and TGF-β1 by examining their mRNA and protein levels and cellular distribution using quantitative co...
Source: Neuropharmacology - March 7, 2016 Category: Drugs & Pharmacology Authors: Zepeda R, Contreras V, Pissani C, Stack K, Vargas M, Owen GI, Lazo OM, Bronfman FC Tags: Neuropharmacology Source Type: research

Alpha-linolenic acid given as enteral or parenteral nutritional intervention against sensorimotor and cognitive deficits in a mouse model of ischemic stroke.
This study evaluated the value of ALA as adjunctive therapy for stroke recovery by comparing whether oral or intravenous supplementation of ALA best support recovery from ischemia. Motor and cognitive deficits were assessed using rotarod, pole and Morris water maze tests. ALA supplementation in diet was better than intravenous treatment in improving motor coordination, but this improvement was not due to a neuroprotective effect since infarct size was not reduced. Both types of ALA supplementation improved spatial learning and memory after stroke. This cognitive improvement correlated with higher survival of hippocampal ne...
Source: Neuropharmacology - April 27, 2016 Category: Drugs & Pharmacology Authors: Bourourou M, Heurteaux C, Blondeau N Tags: Neuropharmacology Source Type: research

Oxidative stress and DNA damage after cerebral ischemia: Potential therapeutic targets to preserve the genome and improve stroke recovery.
Abstract The past two decades have witnessed remarkable advances in oxidative stress research, particularly in the context of ischemic brain injury. Oxidative stress in ischemic tissues compromises the integrity of the genome, resulting in DNA lesions, cell death in neurons, glial cells, and vascular cells, and impairments in neurological recovery after stroke. As DNA is particularly vulnerable to oxidative attack, cells have evolved the ability to induce multiple DNA repair mechanisms, including base excision repair (BER), nucleotide excision repair (NER) and non-homogenous endpoint jointing (NHEJ). Defective DNA...
Source: Neuropharmacology - November 8, 2017 Category: Drugs & Pharmacology Authors: Li P, Anne Stetler R, Leak RK, Shi Y, Li Y, Yu W, Bennett MVL, Chen J Tags: Neuropharmacology Source Type: research

The angiotensin type 2 receptor agonist Compound 21 elicits cerebroprotection in endothelin-1 induced ischemic stroke.
Abstract Evidence indicates that angiotensin II type 2 receptors (AT2R) exert cerebroprotective actions during stroke. A selective non-peptide AT2R agonist, Compound 21 (C21), has been shown to exert beneficial effects in models of cardiac and renal disease, as well as hemorrhagic stroke. Here, we hypothesize that C21 may exert beneficial effects against cerebral damage and neurological deficits produced by ischemic stroke. We determined the effects of central and peripheral administration of C21 on the cerebral damage and neurological deficits in rats elicited by endothelin-1 induced middle cerebral artery occlus...
Source: Neuropharmacology - February 6, 2014 Category: Drugs & Pharmacology Authors: Joseph JP, Mecca AP, Regenhardt RW, Bennion DM, Rodríguez V, Desland F, Patel NA, Pioquinto DJ, Unger T, Katovich MJ, Steckelings UM, Sumners C Tags: Neuropharmacology Source Type: research

PcTx1 affords neuroprotection in a conscious model of stroke inhypertensive rats via selective inhibition of ASIC1a.
Abstract Acid-sensing ion channel 1a (ASIC1a) is the primary acid sensor in mammalian brain and plays a major role in neuronal injury following cerebral ischemia. Evidence that inhibition of ASIC1a might be neuroprotective following stroke was previously obtained using "PcTx1 venom" from the tarantula Psalmopeous cambridgei. We show here that the ASIC1a-selective blocker PcTx1 is present at only 0.4% abundance in this venom, leading to uncertainty as to whether the observed neuroprotective effects were due to PcTx1 blockade of ASIC1a or inhibition of other ion channels and receptors by the hundreds of peptides and...
Source: Neuropharmacology - August 28, 2015 Category: Drugs & Pharmacology Authors: McCarthy CA, Rash LD, Chassagnon IR, King GF, Widdop RE Tags: Neuropharmacology Source Type: research

Lumbrokinase regulates endoplasmic reticulum stress to improve neurological deficits in ischemic stroke
In this study, we aimed to clarify the neuroprotection of lumbrokinase in mice subjected to permanent middle cerebral artery occlusion. Lumbrokinase significantly attenuated infarct volume and improved neurological dysfunction. Lumbrokinase dramatically decreased the expressions of the endoplasmic reticulum (ER) transmembrane receptor protein inositol-requiring enzyme-1 (IRE1) and its downstream transcription factor, XBP-1, caspase-12, and NF-κB activity, thereby significantly inhibiting apoptosis and autophagy and decreasing the NLRP3 inflammasome. Our evidence indicates that post-stroke treatment with lumbrokinase prote...
Source: Neuropharmacology - October 12, 2022 Category: Drugs & Pharmacology Authors: Yi-Hsin Wang Jiuan-Miaw Liao Ke-Min Chen Hsing-Hui Su Pei-Hsun Liu Yi-Hung Chen Yuang-Seng Tsuei Chin-Feng Tsai Shiang-Suo Huang Source Type: research

Prolyl hydroxylase domain inhibitors: can multiple mechanisms be an opportunity for ischemic stroke?
Abstract Stroke and cerebrovascular disease are now the fifth most common cause of death behind other diseases such as heart, cancer and respiratory disease and accounts for approximately 40-50 fatalities per 100,000 people each year in the United States. Currently the only therapy for acute stroke, is intravenous administration of tissue plasminogen activator which was approved in 1996 by the FDA. Surprisingly no new treatments have come on the market since, although endovascular mechanical thrombectomy is showing promising results in trials. Recently focus has shifted towards a preventative therapy rather than t...
Source: Neuropharmacology - December 19, 2018 Category: Drugs & Pharmacology Authors: Lanigan SM, O'Connor JJ Tags: Neuropharmacology Source Type: research

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