Abstract
Stilbazulenyl nitrone (STAZN) is a potent antioxidant that, in a rat model of transient focal cerebral ischemia, confers significant enduring functional and morphological neuroprotection. This study investigated the influence of dose and time of administration on the neuroprotective effects of STAZN in the intraluminal suture model of middle cerebral artery occlusion (MCAo). Dose response: At 2 and 4 h after the onset of MCAo, animals received intravenously either STAZN (low dose = 0.07 mg/kg, n = 8; medium dose = 0.7 mg/kg, n = 9; high dose = 3.5 mg/kg, n = 9), an equivalent volume of vehicle (30% Solutol HS15 and 70% isotonic saline, 0.37 ml/kg, n = 5) or saline (0.37 ml/kg, n = 5). Only the medium dose improved scores (p < 0.05) on a standardized neurobehavioral test at 1, 2 and 3 days after MCAo. Only the medium dose reduced the total infarction (51%, p = 0.014) compared to controls. These results indicate that STAZN exhibits maximal neuroprotection at the 0.7 mg/kg dose. Therapeutic window: STAZN (0.6 mg/kg) dissolved in dimethylsulfoxide was given intra-peritoneally at 2 and 4 h (n = 11), 3 and 5 h (n = 10), 4 and 6 h (n = 10) or 5 and 7 h (n = 7) after the onset of MCAo. Additional doses were given at 24 and 48 h. Vehicle (dimethylsulfoxide, 2.0 ml/kg, n = 6) was administered at 3, 5, 24 and 48 h. STAZN treatment initiated at 2 or 3 h after the onset of MCAo improved neurological scores (p < 0.001) and reduced total infarction (42.2%, p < 0.05) compared to controls.
| Original language | English |
|---|---|
| Pages (from-to) | 101-110 |
| Number of pages | 10 |
| Journal | Brain Research |
| Volume | 1180 |
| Issue number | 1 |
| DOIs | |
| State | Published - Nov 14 2007 |
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Keywords
- Antioxidant
- Cerebral ischemia
- Free radical
- Neuroprotection
- Reperfusion injury
- Stroke
ASJC Scopus subject areas
- Neuroscience(all)
- Clinical Neurology
- Developmental Biology
- Molecular Biology
Cite this
Neuroprotective effect of STAZN, a novel azulenyl nitrone antioxidant, in focal cerebral ischemia in rats : Dose-response and therapeutic window. / Ley, James J.; Belayev, Ludmila; Saul, Isabel; Becker, David A.; Ginsberg, Myron.
In: Brain Research, Vol. 1180, No. 1, 14.11.2007, p. 101-110.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Neuroprotective effect of STAZN, a novel azulenyl nitrone antioxidant, in focal cerebral ischemia in rats
T2 - Dose-response and therapeutic window
AU - Ley, James J.
AU - Belayev, Ludmila
AU - Saul, Isabel
AU - Becker, David A.
AU - Ginsberg, Myron
PY - 2007/11/14
Y1 - 2007/11/14
N2 - Stilbazulenyl nitrone (STAZN) is a potent antioxidant that, in a rat model of transient focal cerebral ischemia, confers significant enduring functional and morphological neuroprotection. This study investigated the influence of dose and time of administration on the neuroprotective effects of STAZN in the intraluminal suture model of middle cerebral artery occlusion (MCAo). Dose response: At 2 and 4 h after the onset of MCAo, animals received intravenously either STAZN (low dose = 0.07 mg/kg, n = 8; medium dose = 0.7 mg/kg, n = 9; high dose = 3.5 mg/kg, n = 9), an equivalent volume of vehicle (30% Solutol HS15 and 70% isotonic saline, 0.37 ml/kg, n = 5) or saline (0.37 ml/kg, n = 5). Only the medium dose improved scores (p < 0.05) on a standardized neurobehavioral test at 1, 2 and 3 days after MCAo. Only the medium dose reduced the total infarction (51%, p = 0.014) compared to controls. These results indicate that STAZN exhibits maximal neuroprotection at the 0.7 mg/kg dose. Therapeutic window: STAZN (0.6 mg/kg) dissolved in dimethylsulfoxide was given intra-peritoneally at 2 and 4 h (n = 11), 3 and 5 h (n = 10), 4 and 6 h (n = 10) or 5 and 7 h (n = 7) after the onset of MCAo. Additional doses were given at 24 and 48 h. Vehicle (dimethylsulfoxide, 2.0 ml/kg, n = 6) was administered at 3, 5, 24 and 48 h. STAZN treatment initiated at 2 or 3 h after the onset of MCAo improved neurological scores (p < 0.001) and reduced total infarction (42.2%, p < 0.05) compared to controls.
AB - Stilbazulenyl nitrone (STAZN) is a potent antioxidant that, in a rat model of transient focal cerebral ischemia, confers significant enduring functional and morphological neuroprotection. This study investigated the influence of dose and time of administration on the neuroprotective effects of STAZN in the intraluminal suture model of middle cerebral artery occlusion (MCAo). Dose response: At 2 and 4 h after the onset of MCAo, animals received intravenously either STAZN (low dose = 0.07 mg/kg, n = 8; medium dose = 0.7 mg/kg, n = 9; high dose = 3.5 mg/kg, n = 9), an equivalent volume of vehicle (30% Solutol HS15 and 70% isotonic saline, 0.37 ml/kg, n = 5) or saline (0.37 ml/kg, n = 5). Only the medium dose improved scores (p < 0.05) on a standardized neurobehavioral test at 1, 2 and 3 days after MCAo. Only the medium dose reduced the total infarction (51%, p = 0.014) compared to controls. These results indicate that STAZN exhibits maximal neuroprotection at the 0.7 mg/kg dose. Therapeutic window: STAZN (0.6 mg/kg) dissolved in dimethylsulfoxide was given intra-peritoneally at 2 and 4 h (n = 11), 3 and 5 h (n = 10), 4 and 6 h (n = 10) or 5 and 7 h (n = 7) after the onset of MCAo. Additional doses were given at 24 and 48 h. Vehicle (dimethylsulfoxide, 2.0 ml/kg, n = 6) was administered at 3, 5, 24 and 48 h. STAZN treatment initiated at 2 or 3 h after the onset of MCAo improved neurological scores (p < 0.001) and reduced total infarction (42.2%, p < 0.05) compared to controls.
KW - Antioxidant
KW - Cerebral ischemia
KW - Free radical
KW - Neuroprotection
KW - Reperfusion injury
KW - Stroke
UR - http://www.scopus.com/inward/record.url?scp=35548984753&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=35548984753&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2007.05.028
DO - 10.1016/j.brainres.2007.05.028
M3 - Article
VL - 1180
SP - 101
EP - 110
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1
ER -