The effect of mannitol and nimodipine treatment in a rat model of temporary focal ischemia.
Male Sprague Dawley rats were anesthetised with Xylazine and Ketamine intraperitoneally. After a lateral craniotomy the cerebral inferior vein was ligated and a very small clip (Biemer clip) was placed on the MCA near its origin for 1 hour. This procedure induced a focal infarction in 100% of the rats. After removal of the clip the lumen of the MCA was patent. The study was divided in 3 randomized groups (control group n = 15; Nimodipine group n = 11, treatment 30 micrograms/hour/kg body-weight; Mannitol group n = 15, treatment 5.4 ml/hour/kg body-weight). Besides heart-rate, ECG and blood pressure we measured the extracellular potassium and calcium concentration with ion-selective microelectrodes; the ICBF was estimated by laser-doppler-flowmeter. The MCA was clipped for 1 hour. After 1 hour of reperfusion the brain was fixated and the volume of infarction was measured by serial slices. Nimodipine or Mannitol treatment started 5 min before clipping the MCA. In rats with Nimodipine treatment the extracellular calcium starts at a significantly higher level (2.3 +/- 0.5 mmol/l) and the decrease during ischemia remains above a level of 1.2 +/- 0.2 mmol/l. The increase in potassium during ischemia and Nimodipine (calculated in change of concentration/time [dc/dt]) is significantly slower than in the control group. In contrast to the post-ischemic hyper- and hypoperfusion in the control group the reperfusion in the Mannitol group is nearly normal. In the control group the infarction volume is 20% of the brain, in the Nimodipine group 15% and in the Mannitol group only 11%. The calcium antagonist Nimodipine and the free-radical scavenger Mannitol therefore promise to be a way to treat or prevent temporary focal cerebral ischemia.
Department of Neurosurgery, Hannover Medical School.
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Rickels
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Gaab
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Heissler
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Dietz
D000818:Animals; D001921:Brain / Q000098:blood supply; D002545:Brain Ischemia / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D005609:Free Radicals; D007262:Infusions, Intravenous; D008297:Male; D008353:Mannitol / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000473:pathology*; D009553:Nimodipine / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism
D005609:Free Radicals; D013481:Superoxides; D008353:Mannitol; D009553:Nimodipine; D011188:Potassium; D002118:Calcium