Neuroimmunophilin Ligand V-10,367 is Neuroprotective after 24-Hour Delayed Administration in a Mouse Model of Diffuse Traumatic Brain Injury

Autor: Megan Ryan Detloff, Nancy C. Kupina, Satavisha Dutta, Edward D. Hall
Rok vydání: 2002
Předmět:
Pathology
medicine.medical_specialty
Time Factors
Pyridines
040301 veterinary sciences
Traumatic brain injury
Administration
Oral
Context (language use)
Striatum
Pharmacology
Ligands
Hippocampus
030226 pharmacology & pharmacy
Neuroprotection
Drug Administration Schedule
0403 veterinary science
Mice
03 medical and health sciences
0302 clinical medicine
Parkinsonian Disorders
Neurofilament Proteins
Neuroplasticity
medicine
Animals
Hippocampus (mythology)
Cerebral Cortex
Dose-Response Relationship
Drug
biology
business.industry
Body Weight
Neurodegeneration
Spectrin
Calpain
04 agricultural and veterinary sciences
medicine.disease
Corpus Striatum
Disease Models
Animal
Neuroprotective Agents
Neurology
1-Methyl-4-phenyl-1
2
3
6-tetrahydropyridine
Brain Injuries
biology.protein
Neurology (clinical)
Cardiology and Cardiovascular Medicine
business
Zdroj: Journal of Cerebral Blood Flow & Metabolism. 22:1212-1221
ISSN: 1559-7016
0271-678X
Popis: 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 α-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.
Databáze: OpenAIRE
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