dihydroergotoxine and Cerebral-Infarction

Ergot alkaloids are commonly used as cerebroprotective drugs. Their efficacy has been demonstrated experimentally in animals submitted to acute cerebral anoxia or ischaemia, at dose levels hugely superior to dose levels usually administered in humans. In the present experiments, dihydroergocryptine (DHEC), a constituent of dihydroergotoxine (DHET), was administered at doses closely related to human doses, preventively (in experiments where animals survived only for a short while after ischaemic insult) or curatively, and its efficacy tested through refined neurological and biochemical evaluation of experimental cerebral ischaemia sequelae. DHEC was administered orally (30 micrograms or 150 micrograms/kg body weight (bwt) twice daily) for 3 days, following transient cerebral ischaemia induced by a 60-min carotid occlusion plus sodium nitroprusside (1.1 mg/rat s.c.) injection, or, in a second experiment, prophylactically (60 micrograms or 300 micrograms/kg bwt/day) for 4 days prior to multiple cerebral infarct induced by sodium arachidonate injection into the left internal carotid artery. The neurological sequelae were evaluated by the Irwin visual placing response or by a battery of behavioural tests. Na-K-ATPase enzyme activity in cerebral homogenates was measured; decreases in this enzyme activity are considered to reflect the neuronal membrane consequences of the neurocell energetic metabolism alterations caused by cerebral ischaemia. Low dose oral DHEC treatment prevented the behavioural abnormalities and memory impairment arising after transient cerebral ischaemia and there was a marked trend in improving the behavioural abnormalities observed in animals submitted to massive cerebral infarction, in spite of the model severity. DHEC prevented reduction in cerebral Na-K-ATPase activity after cerebral multiinfarction. These effects of DHEC were observed with doses and administration route close to the usual therapeutic regimen.

Topics: Animals; Brain; Brain Ischemia; Cerebral Infarction; Dihydroergotoxine; Male; Neurologic Examination; Rats; Rats, Inbred Strains; Sodium-Potassium-Exchanging ATPase

Both age and hypertension are risk factors for the brain. In the presence of a multiple cerebral infarction as obtained by the intra-carotid injection of sodium arachidonate, Hydergine is capable, in the young and old, hypertensive or normotensive rat, of limiting the extent of the edematous reaction, to prevent the intra-cerebral accumulation of Ca++ ions, and limit the fall in cerebral blood flow, all of these facts resulting in a significant improvement in neuromotor behaviour.

Topics: Age Factors; Animals; Brain; Cerebral Infarction; Cerebrovascular Circulation; Dihydroergotoxine; Hypertension; Rats; Risk

Topics: Acute Disease; Animals; Arachidonic Acid; Arachidonic Acids; Blood-Brain Barrier; Brain Ischemia; Cerebral Infarction; Cerebrovascular Circulation; Dihydroergotoxine; Dogs; Ergot Alkaloids; Free Radicals; Membrane Lipids; Rabbits; Rats