Journal article
Neuroimmunophilin Ligand V-10,367 is Neuroprotective after 24-Hour Delayed Administration in a Mouse Model of Diffuse Traumatic Brain Injury
Journal of cerebral blood flow and metabolism, v 22(10), pp 1212-1221
Oct 2002
PMID: 12368660
Featured in Collection : UN Sustainable Development Goals @ Drexel
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 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.
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Details
- Title
- Neuroimmunophilin Ligand V-10,367 is Neuroprotective after 24-Hour Delayed Administration in a Mouse Model of Diffuse Traumatic Brain Injury
- Creators
- Nancy C. Kupina - Pfizer (United States)Megan R. Detloff - Pfizer (United States)Satavisha Dutta - Pfizer (United States)Edward D. Hall - Pfizer (United States)
- Publication Details
- Journal of cerebral blood flow and metabolism, v 22(10), pp 1212-1221
- Publisher
- SAGE Publications
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; College of Medicine; Drexel University
- Web of Science ID
- WOS:000178399200009
- Scopus ID
- 2-s2.0-0036791901
- Other Identifier
- 991020100199004721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Endocrinology & Metabolism
- Hematology
- Neurosciences