Journal
EXPERIMENTAL NEUROLOGY
Volume 215, Issue 1, Pages 119-127Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2008.09.024
Keywords
Diffuse axonal injury; Trauma; Optic nerve; Brain injury; Hypothermia
Categories
Funding
- Research Supported by National Institutes of Health [NS055880]
- Society of Academic Emergency Medicine institutional Research Grant (RWN)
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [K08NS055880] Funding Source: NIH RePORTER
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A prospective, multicenter, randomized trial did not demonstrate improved Outcomes in severe traumatic brain injured patients treated with mild hypothermia [Clifton, G.L., Miller, E.R., Choi, S.C., Levin, H.S., McCauley, S., Smith, K.R., Jr., Muizelaar, J.P., Wagner, F.C., Jr., Marion, D.W., Luerssen, T.G., Chesnut, R.M., Schwartz, M., 2001, Lack of effect of induction of hypothermia after acute brain injury. N. EngI.J. Med. 344, 556-563.]. However, the mean time to target temperature was over 8 h and patient inclusion was based on Glasgow Coma Scale score so brain pathology was likely diverse. There remains significant interest in the benefits of hypothermia after traumatic brain injury (TBI) and, in particular, traumatic axonal injury (TAI). which is believed to significantly contribute to morbidity and mortality of TBI patients. The long-term beneficial effect of mild hypothermia on TAI has not been established. To address this issue, we developed an in vivo rat optic nerve stretch model of TAL Adult male Sprague-Dawley rats underwent unilateral optic nerve stretch at 6, 7 or 8 mm piston displacement. The increased number of axonal swellings and bulbs immunopositive for non-phosphorylated neurofilament (SMI-32) seen four days after injury was statistically significant after 8 mm displacement. Ultrastructural analysis 2 weeks after 8 mm displacement revealed a 45.0% decrease (p<0.0001) in myelinated axonal density in the optic nerve core. There was loss of axons regardless of axon size, Immediate post-injury hypothermia (32 degrees C) for 3 h reduced axonal degeneration ill the core (p = 0.027). There was no differential protection based oil axon size. These results Support further clinical investigation of temporally optimized therapeutic hypothermia after traumatic brain injury. (C) 2008 Elsevier Inc. All rights reserved.
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