Treatment with nimodipine or mannitol reduces programmed cell death and infarct size following focal cerebral ischemia.
The present study was conducted to evaluate the effects of nimodipine and mannitol on infarct size and on the amount of apoptosis after transient focal cerebral ischemia. Focal cerebral ischemia was induced in male Sprague-Dawley rats (weight 300-380 g) by transient occlusion of the right middle cerebral artery (MCAO) using an intraluminal thread model. All animals underwent ischemia for 2 h, followed by 24 h of reperfusion. Group I (n=16) was untreated. Group II (n=16) received 15% mannitol (1 g/kg as bolus) and group III (n=9) received 15 microg/kg/h nimodipine intravenously beginning 15 min prior to MCAO. Twenty-four hours after reperfusion, the brain was taken and sectioned in coronal slices. The slices were stained with H&E and with the transferase dUTP nick-end labeling (TUNEL) technique. Histopathological analysis revealed a significant (P<0.05) decrease in infarct size in the striatum with both drugs: mannitol (group II) 25.4+/-5.9% and nimodipine (group III) 21.5+/-11.0% versus control (group I) 34.9+/-7.0% and in the cortex 2.7+/-2.0% (group II) and 6.3+/-2.4% (group III) versus control 14.4+/-9.0% (group I). The number of apoptotic cells was statistically lower in the therapy groups (group III 9.6, group II 25.8) versus control (group I 57.9) (Mann-Whitney-Wilcoxon U-test Z>1.96, P<0.05). This study indicates that mannitol and nimodipine provide neuroprotection by preventing both the necrotic and apoptotic components of cell death after transient focal cerebral ischemia and may be effective as neuroprotective drugs for cerebrovascular surgery.
Korenkov
A I
AI
Department of Neurosurgery, University of Greifswald, Germany. korenkow@mail.uni-greifswald.de
Pahnke
J
J
Frei
K
K
Warzok
R
R
Schroeder
H W
HW
Frick
R
R
Muljana
L
L
Piek
J
J
Yonekawa
Y
Y
Gaab
M R
MR
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D003342:Corpus Striatum / Q000473:pathology; D005260:Female; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling; D002546:Ischemic Attack, Transient / Q000150:complications*; D008353:Mannitol / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009553:Nimodipine / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002121:Calcium Channel Blockers; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D008353:Mannitol; D009553:Nimodipine