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Immediate short-duration hypothermia provides long-term protection in an in vivo model of traumatic axonal injury.

Abstract：

: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. Engl. 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 TAI. 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 in the core (p=0.027). There was no differential protection based on axon size. These results support further clinical investigation of temporally optimized therapeutic hypothermia after traumatic brain injury.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Ma M,Matthews BT,Lampe JW,Meaney DF,Shofer FS,Neumar RW

doi

10.1016/j.expneurol.2008.09.024

subject

Has Abstract

pub_date

2009-01-01 00:00:00

pages

119-27

issue

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(08)00373-7

journal_volume

215

pub_type

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Immediate short-duration hypothermia provides long-term protection in an in vivo model of traumatic axonal injury.