sm-346 and Stroke

sm-346 has been researched along with Stroke* in 3 studies

Other Studies

3 other study(ies) available for sm-346 and Stroke

ArticleYear
Activation of σ1 and σ2 receptors by afobazole increases glial cell survival and prevents glial cell activation and nitrosative stress after ischemic stroke.
    Journal of neurochemistry, 2016, Volume: 139, Issue:3

    Activation of sigma receptors at delayed time points has been shown to decrease injury following ischemic stroke. The mixed σ1/σ2 receptor agonist, 5-ethoxy-2-[2-(morpholino)-ethylthio]benzimidazole (afobazole), provides superior long-term outcomes compared to other σ ligands in the rat middle cerebral artery occlusion (MCAO) stroke model. Experiments using the MCAO model were carried out to determine the molecular mechanism involved in the beneficial effects of afobazole. Administration of afobazole (3 mg/kg) at delayed time points post-stroke significantly increased the number of microglia and astrocytes detected in the ipsilateral hemisphere at 96 h post-surgery. Morphological analysis of the microglia indicated that a greater number of these cells were found in the ramified resting state in MCAO animals treated with afobazole relative to MCAO vehicle controls. Similarly, fewer reactive astrocytes were detected in the injured hemisphere of afobazole-treated animals. Both the enhanced survival and reduced activation of glial cells were abolished by co-application of either a σ1 (BD-1063) or a σ2 (SM-21) receptor antagonist with afobazole. To gain further insight into the mechanisms by which afobazole lessens stroke injury, we probed the brain sections for markers of neuroinflammation (tumor necrosis factor α) and nitrosative stress (S-nitrosocysteine). Data show that afobazole significantly reduces S-nitrosocysteine levels, but does not alter tumor necrosis factor α expression 96 h after an ischemic stroke. Taken together our data indicate that afobazole acting via both σ1 and σ2 receptors decreases stroke injury by enhancing glial cell survival, blocking ischemia-induced glial cell activation, and decreasing nitrosative stress.

    Topics: Animals; Astrocytes; Benzimidazoles; Brain; Brain Ischemia; Butyrates; Cell Survival; Cysteine; Infarction, Middle Cerebral Artery; Macrophage Activation; Morpholines; Neuroglia; Neuroprotective Agents; Piperazines; Rats; Receptors, sigma; S-Nitrosothiols; Sigma-1 Receptor; Stroke; Tropanes

2016
Treatment with afobazole at delayed time points following ischemic stroke improves long-term functional and histological outcomes.
    Neurobiology of disease, 2014, Volume: 62

    There is currently a significant lack of therapeutic options for acute ischemic stroke, and no drug has been approved for treating patients at delayed time points (≥6h post-stroke). Afobazole, an anxiolytic currently used clinically in Russia, has been shown to reduce neuronal and glial cell injury in vitro following ischemia. Experiments using the permanent middle cerebral artery occlusion (MCAO) rat model were carried out to determine if afobazole can reduce ischemic stroke damage in vivo and expand the therapeutic window for stroke treatment. Post-stroke (24h) application of afobazole (0.3-3mg/kg) significantly decreased infarct volume at 96h post-surgery, as determined by Fluoro-Jade and NeuN staining of brain sections. Moreover, afobazole helped preserve both the levels and normal histological distribution of myelin basic protein, indicating a reduction in white matter injury. A time-dependence study showed that either pre-treatment or treatment started 6 to 48h post-stroke with the drug yields improved outcomes at 96h. The decrease in infarct volume produced by afobazole was blocked by the application of either a σ-1 (BD 1063, 30mg/kg) or a σ-2 (SM-21, 1mg/kg) antagonist, indicating that both receptor subtypes are involved in the effects of afobazole. Treatment with afobazole starting at 24h post-stroke resulted in enhanced survival one month following surgery. Behavioral testing of animals 28-32days post-surgery using the elevated body swing and forelimb grip-strength tests revealed that treatment with afobazole starting 24h post-stroke significantly reduces behavioral deficits caused by ischemic stroke. The increase in survival and improved functional outcomes are accompanied by a reduction in infarct volume, as determined by thionin staining of brain sections. Taken together, our data support the use of afobazole as a post-stroke pharmacological agent to expand the current therapeutic window.

    Topics: Animals; Benzimidazoles; Brain Ischemia; Hand Strength; Infarction, Middle Cerebral Artery; Male; Morpholines; Rats; Rats, Sprague-Dawley; Receptors, sigma; Stroke; Treatment Outcome

2014
Neuroprotective effect of afobazole on rats with bilateral local photothrombosis of vessels in the prefrontal cortex.
    Bulletin of experimental biology and medicine, 2008, Volume: 145, Issue:2

    We studied the neuroprotective effect of a new selective anxiolytic afobazole on rats with bilateral focal ischemic stroke in the prefrontal cortex caused by photothrombosis. Intraperitoneal injection of 5 mg/kg afobazole 1 h after surgery and over the next 8 days (daily treatment) produced a neuroprotective effect. Afobazole was far superior to the reference cerebroprotective drug cavinton (4 mg/kg) by neuroprotective activity.

    Topics: Animals; Anti-Anxiety Agents; Benzimidazoles; Blood Vessels; Brain Ischemia; Injections, Intraperitoneal; Light; Male; Mice; Morpholines; Motor Activity; Neuroprotective Agents; Prefrontal Cortex; Rats; Stroke

2008