Document Detail

The combination of either tempol or FK506 with delayed hypothermia: implications for traumatically induced microvascular and axonal protection.
MedLine Citation:
PMID:  21521034     Owner:  NLM     Status:  MEDLINE    
Following traumatic brain injury (TBI), inhibition of reactive oxygen species and/or calcineurin can exert axonal and vascular protection. This protection proves optimal when these strategies are used early post-injury. Recent work has shown that the combination of delayed drug administration and delayed hypothermia extends this protection. Here we revisit this issue in TBI using the nitroxide antioxidant Tempol, or the immunophilin ligand FK506, together with delayed hypothermia, to determine their effects upon cerebral vascular reactivity and axonal damage. Animals were subjected to TBI and treated with Tempol at 30 or 90 min post-injury, or 90 min post-injury with concomitant mild hypothermia (33°C). Another group of animals were treated in the same fashion with the exception that they received FK506. Cranial windows were placed to assess vascular reactivity over 6 h post-injury, when the animals were assessed for traumatically induced axonal damage. Vasoreactivity was preserved by early Tempol administration; however, this benefit declined with time. The coupling of hypothermia and delayed Tempol, however, exerted significant vascular protection. The use of early and delayed FK506 provided significant vascular protection which was not augmented by hypothermia. The early administration of Tempol provided dramatic axonal protection that was not enhanced with hypothermia. Early and delayed FK506 provided significant axonal protection, although this protection was not enhanced by delayed hypothermia. The current investigation supports the premise that Tempol coupled with hypothermia extends its benefits. While FK506 proved efficacious with early and delayed administration, it did not provide either increased vascular or axonal benefit with hypothermia. These studies illustrate the potential benefits of Tempol coupled to delayed hypothermia. However, these findings do not transfer to the use of FK506, which in previous studies proved beneficial when coupled with hypothermia. These divergent results may be a reflection of the different animal models used and/or their associated injury severity.
Motoki Fujita; Yasutaka Oda; Enoch P Wei; John T Povlishock
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of neurotrauma     Volume:  28     ISSN:  1557-9042     ISO Abbreviation:  J. Neurotrauma     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-19     Completed Date:  2012-05-21     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  8811626     Medline TA:  J Neurotrauma     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1209-18     Citation Subset:  IM    
Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA.
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MeSH Terms
Axons / drug effects*,  pathology,  physiology
Brain Injuries / drug therapy*,  physiopathology
Combined Modality Therapy / methods*
Cyclic N-Oxides / pharmacology*,  therapeutic use
Disease Models, Animal
Hypothermia, Induced / methods*
Immunosuppressive Agents / pharmacology,  therapeutic use
Microcirculation / drug effects,  physiology
Neuroprotective Agents / pharmacology,  therapeutic use
Rats, Sprague-Dawley
Spin Labels
Tacrolimus / pharmacology*,  therapeutic use
Grant Support
Reg. No./Substance:
0/Cyclic N-Oxides; 0/Immunosuppressive Agents; 0/Neuroprotective Agents; 0/Spin Labels; 109581-93-3/Tacrolimus; 2226-96-2/tempol

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