Abstract
The purpose of this study was to evaluate the effects of MRZ 2/579, an uncompetitive N-methyl-D-aspartate antagonist, on infarct size, extent of swelling and neurological deficit in a model of transient middle cerebral artery occlusion in rats. Physiologically controlled Sprague-Dawley rats received 2 h MCAo by retrograde insertion of an intraluminal suture coated with poly-L-lysine. The agent (MRZ 2/579) or vehicle (sodium chloride 0.9%) was administered i.v. immediately after suture removal following a 2-h period of MCAo. Two experimental groups were studied: group A was treated by vehicle (bolus infusion:1 ml/kg for 10 min followed by infusion of 6 ml/kg/h over 6 h). Group B was treated by MRZ 2/579 (bolus infusion:10 mg/kg for 10 min followed by infusion of 6 mg/kg/h over 6 h). The neurological status was evaluated during occlusion (at 60 min) and daily for 3 days after MCAo. Brains were then perfusion-fixed, and infarct volumes and brain swelling were determined. MRZ 2/579 significantly improved the neurological score compared to vehicle-treated rats at 48 h (6.2±0.6 and 8.7±0.5, respectively; P<0.004) and 72 h after MCAo (5.2±0.6 and 8.4±0.5, respectively; P<0.001). Treatment with MRZ 2/579 also significantly reduced total infarct volume (29.3±11.1 and 83.2±16.5 mm3, respectively; P<0.01), cortical infarct volume (24.8±11.2 and 70.0±18.0 mm3, respectively; P<0.04) and subcortical infarction (21.2±4.1 and 49.6±4.5 mm3, respectively; P<0.0002). Brain swelling was also markedly reduced compared with vehicle-treated rats (4.7±1.3 and 10.8±2.1%, respectively; P<0.02). These results demonstrate that treatment with MRZ 2/579, when administered promptly after reperfusion, confers neuroprotective effects on infarct volume, brain swelling, and neurological score compared to the vehicle group. Themes: Disorders of the nervous system. Topics: Ischemia. Copyright (C) 2000 Elsevier Science B.V.
| Original language | English |
|---|---|
| Pages (from-to) | 111-119 |
| Number of pages | 9 |
| Journal | Brain Research |
| Volume | 862 |
| Issue number | 1-2 |
| DOIs | |
| State | Published - Apr 17 2000 |
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Keywords
- Focal cerebral ischemia
- Image-analysis
- MRZ 2/579
- Neuroprotection
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
MRZ 2/579, a novel uncompetitive N-methyl-D-aspartate antagonist, reduces infarct volume and brain swelling and improves neurological deficit after focal cerebral ischemia in rats. / Liu, Yitao; Belayev, Ludmila; Zhao, Weizhao; Busto, Raul; Ginsberg, Myron.
In: Brain Research, Vol. 862, No. 1-2, 17.04.2000, p. 111-119.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - MRZ 2/579, a novel uncompetitive N-methyl-D-aspartate antagonist, reduces infarct volume and brain swelling and improves neurological deficit after focal cerebral ischemia in rats
AU - Liu, Yitao
AU - Belayev, Ludmila
AU - Zhao, Weizhao
AU - Busto, Raul
AU - Ginsberg, Myron
PY - 2000/4/17
Y1 - 2000/4/17
N2 - The purpose of this study was to evaluate the effects of MRZ 2/579, an uncompetitive N-methyl-D-aspartate antagonist, on infarct size, extent of swelling and neurological deficit in a model of transient middle cerebral artery occlusion in rats. Physiologically controlled Sprague-Dawley rats received 2 h MCAo by retrograde insertion of an intraluminal suture coated with poly-L-lysine. The agent (MRZ 2/579) or vehicle (sodium chloride 0.9%) was administered i.v. immediately after suture removal following a 2-h period of MCAo. Two experimental groups were studied: group A was treated by vehicle (bolus infusion:1 ml/kg for 10 min followed by infusion of 6 ml/kg/h over 6 h). Group B was treated by MRZ 2/579 (bolus infusion:10 mg/kg for 10 min followed by infusion of 6 mg/kg/h over 6 h). The neurological status was evaluated during occlusion (at 60 min) and daily for 3 days after MCAo. Brains were then perfusion-fixed, and infarct volumes and brain swelling were determined. MRZ 2/579 significantly improved the neurological score compared to vehicle-treated rats at 48 h (6.2±0.6 and 8.7±0.5, respectively; P<0.004) and 72 h after MCAo (5.2±0.6 and 8.4±0.5, respectively; P<0.001). Treatment with MRZ 2/579 also significantly reduced total infarct volume (29.3±11.1 and 83.2±16.5 mm3, respectively; P<0.01), cortical infarct volume (24.8±11.2 and 70.0±18.0 mm3, respectively; P<0.04) and subcortical infarction (21.2±4.1 and 49.6±4.5 mm3, respectively; P<0.0002). Brain swelling was also markedly reduced compared with vehicle-treated rats (4.7±1.3 and 10.8±2.1%, respectively; P<0.02). These results demonstrate that treatment with MRZ 2/579, when administered promptly after reperfusion, confers neuroprotective effects on infarct volume, brain swelling, and neurological score compared to the vehicle group. Themes: Disorders of the nervous system. Topics: Ischemia. Copyright (C) 2000 Elsevier Science B.V.
AB - The purpose of this study was to evaluate the effects of MRZ 2/579, an uncompetitive N-methyl-D-aspartate antagonist, on infarct size, extent of swelling and neurological deficit in a model of transient middle cerebral artery occlusion in rats. Physiologically controlled Sprague-Dawley rats received 2 h MCAo by retrograde insertion of an intraluminal suture coated with poly-L-lysine. The agent (MRZ 2/579) or vehicle (sodium chloride 0.9%) was administered i.v. immediately after suture removal following a 2-h period of MCAo. Two experimental groups were studied: group A was treated by vehicle (bolus infusion:1 ml/kg for 10 min followed by infusion of 6 ml/kg/h over 6 h). Group B was treated by MRZ 2/579 (bolus infusion:10 mg/kg for 10 min followed by infusion of 6 mg/kg/h over 6 h). The neurological status was evaluated during occlusion (at 60 min) and daily for 3 days after MCAo. Brains were then perfusion-fixed, and infarct volumes and brain swelling were determined. MRZ 2/579 significantly improved the neurological score compared to vehicle-treated rats at 48 h (6.2±0.6 and 8.7±0.5, respectively; P<0.004) and 72 h after MCAo (5.2±0.6 and 8.4±0.5, respectively; P<0.001). Treatment with MRZ 2/579 also significantly reduced total infarct volume (29.3±11.1 and 83.2±16.5 mm3, respectively; P<0.01), cortical infarct volume (24.8±11.2 and 70.0±18.0 mm3, respectively; P<0.04) and subcortical infarction (21.2±4.1 and 49.6±4.5 mm3, respectively; P<0.0002). Brain swelling was also markedly reduced compared with vehicle-treated rats (4.7±1.3 and 10.8±2.1%, respectively; P<0.02). These results demonstrate that treatment with MRZ 2/579, when administered promptly after reperfusion, confers neuroprotective effects on infarct volume, brain swelling, and neurological score compared to the vehicle group. Themes: Disorders of the nervous system. Topics: Ischemia. Copyright (C) 2000 Elsevier Science B.V.
KW - Focal cerebral ischemia
KW - Image-analysis
KW - MRZ 2/579
KW - Neuroprotection
UR - http://www.scopus.com/inward/record.url?scp=0034678533&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034678533&partnerID=8YFLogxK
U2 - 10.1016/S0006-8993(00)02078-3
DO - 10.1016/S0006-8993(00)02078-3
M3 - Article
C2 - 10799675
AN - SCOPUS:0034678533
VL - 862
SP - 111
EP - 119
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1-2
ER -