quetiapine-fumarate and Brain-Ischemia

White matter impairment is a feature of vascular depression. The anti-psychotic quetiapine has been shown to enhance the therapeutic effects of anti-depressants on vascular depression, but the mechanism remains unknown. In this study, we found that 2 weeks of treatment with quetiapine prior to bilateral carotid artery occlusion and reperfusion, in an animal model of vascular depression, resulted in reduced myelin breakdown and oligodendrocyte loss compared to placebo-treated mice on post-operative day (POD) 7. For late stage of recovery (POD40), quetiapine treatment resulted in enhanced oligodendrocyte maturation relative to placebo. The results suggest that quetiapine is a potential intervention for oligodendrocyte damage and this may contribute to its anti-depressant effects through white matter protection in vascular depression.

Topics: Analysis of Variance; Animals; Antigens; Antipsychotic Agents; Brain Ischemia; Bromodeoxyuridine; Carotid Artery Diseases; Cell Differentiation; Dibenzothiazepines; Disease Models, Animal; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Hippocampus; Male; Mice; Myelin Basic Protein; Myelin Sheath; Oligodendroglia; Proteoglycans; Quetiapine Fumarate; Time Factors

The present paper reports on a 68-year-old man with a 10-year history of parkinsonism who developed hallucinations and delusions after admission to an intensive care unit for the treatment of organophosphate intoxication. His initial diagnosis was delirium. On the basis of brain computed tomography findings and clinical symptoms, we diagnosed drug-induced psychosis in parkinsonism with multiple cysts in the bilateral striata.

Topics: 3-Iodobenzylguanidine; Aged; Antiparkinson Agents; Antipsychotic Agents; Brain Ischemia; Delirium; Delusions; Diagnosis, Differential; Dibenzothiazepines; Dominance, Cerebral; Drug Therapy, Combination; Encephalomalacia; Hallucinations; Humans; Levodopa; Magnetic Resonance Imaging; Male; Neostriatum; Neurologic Examination; Organophosphate Poisoning; Parkinsonian Disorders; Psychoses, Substance-Induced; Quetiapine Fumarate; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

Previously, we showed that quetiapine, an atypical antipsychotic drug, significantly attenuated neurodegeneration induced by global cerebral ischemia (GCI). The present work investigates the effects of quetiapine on neurogenesis.. Mice were treated with quetiapine (10 or 20 mg/kg/day; intraperitoneal injection) for 2 weeks and then subjected to GCI on day 15. Seven days after GCI, the mice were killed. Neuronal injury and neurogenesis were analysed using hematoxylin-eosin and 5-bromo-20-deoxyuridine stainings. Levels of nuclear factor kappaB (NF-kappaB) p65/p50 expressions were determined by immunohistochemistry and Western blot analysis.. Global cerebral ischemia resulted in neuronal injury, neurogenesis and NF-kappaB p65/p50 expressions in hippocampus, especially in the dentate gyrus. Pre-administration of quetiapine significantly alleviated neuronal injury, while inhibiting neurogenesis and down-regulating NF-kappaB p65/p50 expression.. NF-kappaB plays a key role in regulating neuron damage and neurogenesis. This work suggests that down-regulation of NF-kappaB expression may be one of the mechanisms by which quetiapine inhibits neurogenesis.

Topics: Animals; Antipsychotic Agents; Brain Ischemia; Bromodeoxyuridine; Cell Count; Cell Proliferation; Dibenzothiazepines; Disease Models, Animal; Dose-Response Relationship, Drug; Gene Expression Regulation; Hippocampus; Male; Mice; Mice, Inbred ICR; Neurogenesis; NF-kappa B p50 Subunit; Quetiapine Fumarate; Transcription Factor RelA

Topics: Acromegaly; Acute Disease; Adenoma; Adult; Antipsychotic Agents; Basal Ganglia; Brain Ischemia; Chorea; Diabetes Complications; Diabetic Ketoacidosis; Dibenzothiazepines; Dyskinesias; Female; Growth Hormone; Humans; Hyperglycemia; Insulin; Magnetic Resonance Imaging; Pituitary Gland; Pituitary Neoplasms; Quetiapine Fumarate; Syndrome

Recently, we have reported that quetiapine, an atypical antipsychotic drug, prevents memory impairment and hippocampus neurodegeneration induced by global cerebral ischemia (GCI). In the present study, we examined the possible effects of quetiapine on other behavioural deficits, including the depressive and anxiolytic-like behavioural consequences of GCI. Mice were treated with quetiapine (5 or 10mg/kg/day; intraperitoneal (i.p.)) for 14 days. On Day 15, the animals were subjected to GCI. GCI resulted in a decrease of striatal tyrosine hydroxylase (TH) immunostaining and induced depressive and anxiolytic-like behavioural changes. The behavioural changes were indicated by a significant increase in the immobility duration in a tail-suspension test, and an increase in the time spent in the light box in a light/dark box test. Pre-administration of quetiapine significantly alleviated the decreased TH immunostaining and attenuated the depressive and anxiolytic-like behavioural changes induced by GCI. These results enhance our understanding about the mechanisms of quetiapine and suggest a wider perspective for the clinical use of quetiapine.

Topics: Analysis of Variance; Animals; Antipsychotic Agents; Anxiety; Behavior, Animal; Brain Ischemia; Depression; Dibenzothiazepines; Disease Models, Animal; Exploratory Behavior; Hindlimb Suspension; Male; Mice; Putamen; Quetiapine Fumarate; Tyrosine 3-Monooxygenase