Abstract | OBJECTIVE: METHODS: To investigate the efficacy of LY341122 in this parasagittal fluid percussion model (1.8-2.1 atm), the rats received oral administration of LY341122 (100 mg/kg) or vehicle 2 hours before and 4 hours after TBI (each group, n = 7). To investigate the therapeutic window for treatment, rats were treated with LY341122 or vehicle for 20 hours by femoral vein infusion starting at 5 minutes, 30 minutes, or 3 hours after TBI (each group, n = 5). Three days after injury, analysis of contusion volumes and the frequency of damaged cortical neurons was conducted. RESULTS:
Oral administration of LY341122 before and after TBI led to a significant reduction in overall contusion volume (3.28 mm3+/-0.75 mm3 [mean +/- standard error of the mean] versus 1.32 mm3 +/- 0.33 mm3; P < 0.05) and also reduced the frequency of damaged cortical neurons (1191.7 +/- 267.1 versus 474.6 +/- 80.2; P < 0.05). In the second experiment, rats treated with LY341122 at 5 minutes or 30 minutes after TBI also demonstrated a significant reduction (P < 0.05) in contusion volume (1.92 mm3 +/- 0.64 mm3 or 1.59 mm3 +/- 0.50 mm3, respectively) compared with vehicle-treated rats (4.32 mm3 +/- 1.15 mm3). A significant reduction in total cortical necrotic neuron counts was also demonstrated in the 5-minute group (2243.8 +/- 265.3 versus 1457.8 +/- 265.3; P < 0.05). In contrast, histopathological outcome was not significantly improved when treatment was delayed until 3 hours after TBI. CONCLUSION: These data reinforce the hypothesis that lipid peroxidation and reactive oxygen species participate in the acute pathogenesis of TBI. Treatment delayed until 3 hours after TBI did not provide significant histopathological protection.
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Authors | K Wada, O F Alonso, R Busto, J Panetta, J A Clemens, M D Ginsberg, W D Dietrich |
Journal | Neurosurgery
(Neurosurgery)
Vol. 45
Issue 3
Pg. 601-8
(Sep 1999)
ISSN: 0148-396X [Print] United States |
PMID | 10493379
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- LY 341122
- Oxazoles
- Carbon Dioxide
- Oxygen
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Topics |
- Administration, Oral
- Animals
- Blood Pressure
(drug effects)
- Brain
(drug effects, pathology)
- Brain Injuries
(drug therapy, pathology, physiopathology)
- Carbon Dioxide
(blood)
- Lipid Peroxidation
(drug effects)
- Male
- Oxazoles
(administration & dosage, therapeutic use)
- Oxygen
(blood)
- Rats
- Rats, Sprague-Dawley
- Time Factors
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