Protective effect of cerebrocrast on rat brain ischaemia induced by occlusion of both common carotid arteries.
Diabetes mellitus is accompanied by several cardiovascular complications including atherosclerosis, cerebral ischaemia and stroke. We examined the neuroprotective effect of a 1,4-dihydropyridine derivative cerebrocrast (C, a new antidiabetic agent, synthesized in the Latvian Institute of Organic Synthesis) on the level of ATP in the brain, and on changes of the EEG and ECG, as well as blood pressure parameters in anaesthetized Wistar male rats before and during 10-min occlusion of both common carotid arteries. Cerebrocrast was administered i.v. at doses of 1.0 and 10 microg/kg in the v. femoralis 20 min prior to ischaemia. After 10-min ischaemia animals were decapitated and the brain was immediately frozen in liquid nitrogen and subsequently used for analysis of changes of ATP contention. Cerebrocrast, administered at doses of 1.0 and 10 microg/kg 20 min prior to occlusion of both common carotid arteries, completely prevented a fall in the ATP content of brain compared with the control rats. In control rats the content of ATP in brain during ischaemia decreased from 2.77 +/- 0.22 (basal level) to 1.74 +/- 0.20 micromol/g as a result of ischaemia. By administration of cerebrocrast 20 min before occlusion of the arteries, the content of ATP in the brain remained at the level of preischaemia (1.0 microg/kg C + ischaemia 2.82 +/- 0.36; 10 microg/kg C + ischaemia 2.42 +/- 0.22 micromol/g). Analysis of EEG parameters both before and during 10 min of occlusion showed that at a C dose of 1.0 microg/kg before occlusion produced a regular alpha rhythm during ischaemia and prevented cerebral bioelectric activity from significant changes. The depression of basal rhythm was observed at a C dose of 10 microg/kg during ischaemia in two rats out of six as well as an increase in the ECG ST segment above the isoelectric line. Blood pressure was decreased by about 10-20 mm Hg. We propose that pretreatment of rats with cerebrocrast at doses of 1.0 or 10 microg/kg 20 min prior to ischaemia can prevent ischaemic damage of rat brain, maintain necessary energy consumption, promote ATP production in brain cells, and prevent significant changes in EEG and ECG parameters. These properties are important in diabetes mellitus and its evoked cardiovascular complications as stroke, ischaemia, etc.
Briede
Janïna
J
Latvian Institute of Organic Synthesis, Latvial.
Duburs
Gunárs
G
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D016893:Carotid Stenosis / Q000150:complications / Q000503:physiopathology; D004095:Dihydropyridines / Q000494:pharmacology*; D004562:Electrocardiography / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000503:physiopathology / Q000517:prevention & control
D004095:Dihydropyridines; D018696:Neuroprotective Agents; C073838:2,6-dimethyl-3,5-bis(2'-propoxyethoxycarbonyl)-4-(2''-difluoromethoxyphenyl)-1,4-dihydropyridine; D000255:Adenosine Triphosphate