Back to Search
Start Over
AIT-082 and methylprednisolone singly, but not in combination, enhance functional and histological improvement after acute spinal cord injury in rats.
- Source :
-
International journal of immunopathology and pharmacology [Int J Immunopathol Pharmacol] 2004 Sep-Dec; Vol. 17 (3), pp. 353-66. - Publication Year :
- 2004
-
Abstract
- Extracellular non-adenine based purines are neuroprotective. Preliminary studies indicate that administration of the synthetic purine 4-[[3-(1,6 dihydro-6-oxo-9-purine-9-yl)-1-oxypropyl] amino] benzoic acid (AIT-082, leteprinim potassium) to rats immediately after acute spinal cord injury (SCI), improves functional outcome. The effects of potential new agents are often compared to methylprednisolone (MPSS). We evaluated the effects of AIT-082 and MPSS, separately and in combination, on the functional and morphological outcome of acute SCI in adult rats. After standardized T11-12 spinal cord compression rats were given intraperitoneally one of the following: vehicle (saline); MPSS (30 mg/kg or 60 mg/kg body weight, first dose 15 min after crush); AIT-082 (60 mg/kg body weight daily, first dose 15 min after crush); or AIT-082 plus MPSS. After 1, 3, or 21 days, the rats were perfused for histological analysis. AIT-082 administrations significantly reduced locomotor impairment from 121 days post-operatively. At 1 and 3 days post injury, AIT-082-treatment reduced tissue swelling, tissue loss and astrogliosis at the injured cords but did not alter the extent of hemorrhage and the number of macrophages and/or microglia. MPSS reduced hemorrhage and the number of macrophages and/or microglia, but did not alter astrogliosis. At 21 days, either AIT-082 or MPSS administration improved function and morphology similarly (less tissue loss and astrogliosis). In contrast, administration of AIT-082 and MPSS together abolished the beneficial effects observed when either drug was given individually. These results suggest that MPSS and AIT-082 may exert their beneficial effects through different and potentially antagonistic pathways.
- Subjects :
- Aminobenzoates administration & dosage
Animals
Behavior, Animal drug effects
Behavior, Animal physiology
Drug Interactions
Female
Gliosis pathology
Hindlimb physiology
Hypoxanthines administration & dosage
Immunohistochemistry
Locomotion physiology
Methylprednisolone administration & dosage
Nerve Crush
Neuroprotective Agents administration & dosage
Rats
Rats, Wistar
Spinal Cord Injuries pathology
Spinal Cord Injuries physiopathology
Treatment Outcome
Aminobenzoates therapeutic use
Anti-Inflammatory Agents therapeutic use
Hypoxanthines therapeutic use
Methylprednisolone therapeutic use
Neuroprotective Agents therapeutic use
Spinal Cord Injuries drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0394-6320
- Volume :
- 17
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- International journal of immunopathology and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 15461869
- Full Text :
- https://doi.org/10.1177/039463200401700315