Abstract |
The authors present two studies that investigate the biochemical and histologic effects of the nonimmunosuppressive neuroimmunophilin (NIMM) ligand V-10,367 in a mouse model of traumatic brain injury (TBI). In study 1, the authors examined the effect of V-10,367 (50 mg/kg x 2 per day, by mouth) on neurofilament M (NFM) protein levels and on alpha-spectrin breakdown products (SBDPs) when dosed for 2 days, starting 24 hours after TBI and killed on day 3. In study 2, V-10,367 was given for 10 days, starting 24 hours after TBI and the mice killed 6 weeks after TBI, to measure the extent of neurodegeneration (amino CuAg stain). The results in study 1 revealed that V-10,367-treatment significantly increased NFM protein levels in both sham and TBI mice. In addition, V-10,367 attenuated SBDP 150 levels in the cortex, striatum, and hippocampus. The results of study 2 indicated that TBI mice treated with V-10,367 demonstrated significantly less neurodegeneration compared to injured, vehicle-treated mice. In summary, these results suggest that NIMMs may be neuroprotective indirectly through inhibition of calpain-mediated cytoskeletal damage and perhaps via maintenance of neuronal plasticity. In the context of this mouse model of TBI, the therapeutic window for V-10,367's positive effects is at least 24 hours after injury, which, in the case of TBI models, is largely unprecedented for a neuroprotective compound.
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Authors | Nancy C Kupina, Megan R Detloff, Satavisha Dutta, Edward D Hall |
Journal | Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
(J Cereb Blood Flow Metab)
Vol. 22
Issue 10
Pg. 1212-21
(Oct 2002)
ISSN: 0271-678X [Print] United States |
PMID | 12368660
(Publication Type: Journal Article)
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Chemical References |
- Ligands
- Neurofilament Proteins
- Neuroprotective Agents
- Pyridines
- V 10367
- Spectrin
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
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Topics |
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
- Administration, Oral
- Animals
- Body Weight
(drug effects)
- Brain Injuries
(drug therapy)
- Cerebral Cortex
(drug effects, metabolism)
- Corpus Striatum
(drug effects, metabolism)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Drug Administration Schedule
- Hippocampus
(drug effects, metabolism)
- Ligands
- Mice
- Neurofilament Proteins
(drug effects, metabolism)
- Neuroprotective Agents
(therapeutic use)
- Parkinsonian Disorders
(chemically induced, drug therapy)
- Pyridines
(therapeutic use)
- Spectrin
(metabolism)
- Time Factors
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