olanzapine and Brain-Ischemia

We have previously shown the neuroprotective effect of atypical antipsychotic agents by experimental cerebral ischemia. However the impact of their high dose related side effects on their low dosage related neuroprotectivity is still unknown.We evaluated the possible neuroprotective effects of high dose olanzapine (10mg/kg) treatment on ischemic brain injury 24 hr after permanent cerebral ischemia. Olanzapine showed neither a neuroprotective nor a neurotoxic effect after focal cerebral ischemia. This finding could suggest that dose related side effect of olanzapine could involve a restriction of its neuroprotective effect unlike lower doses that have been reported to have neuroprotective effect.

Topics: Animals; Benzodiazepines; Brain Infarction; Brain Ischemia; Dose-Response Relationship, Drug; Laser-Doppler Flowmetry; Male; Mice; Neurons; Neuroprotective Agents; Olanzapine; Staining and Labeling; Tetrazolium Salts

Atypical antipsychotic drugs are widely used in the treatment of schizophrenia. These agents are discovered to have some additional beneficial effects beyond their effectiveness as antipsychotic drugs. Among these initially unexpected effects are their potential effects as mood stabilizers in bipolar disorder and their efficacy in improving long-term outcome in schizophrenia. These effects recently raised the question whether these drugs may also have some neuroprotective effect in the brain. To examine this matter, in this study we evaluated the neuroprotective effect of olanzapine after permanent focal cerebral ischemia. Anaesthetized male C57BL/6j mice were submitted to permanent thread occlusion of the middle cerebral artery (MCA). Olanzapine (0.1 and 1 mg/kg) or vehicle was applied intraperitoneally just after permanent ischemia. Twenty-four hours after permanent ischemia, brain injury was evaluated by triphenyltetrazolium chloride staining (TTC). Olanzapine (0.1 and 1 mg/kg) showed significant neuroprotection after permanent focal cerebral ischemia.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Brain; Brain Ischemia; Cerebral Infarction; Cerebrovascular Circulation; Cytoprotection; Disease Models, Animal; Dose-Response Relationship, Drug; Infarction, Middle Cerebral Artery; Laser-Doppler Flowmetry; Male; Mice; Nerve Degeneration; Neuroprotective Agents; Olanzapine; Tetrazolium Salts; Treatment Outcome