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Review
. 2017 Nov 20:6:2031.
doi: 10.12688/f1000research.12025.1. eCollection 2017.

Is temperature an important variable in recovery after mild traumatic brain injury?

Affiliations
Review

Is temperature an important variable in recovery after mild traumatic brain injury?

Coleen M Atkins et al. F1000Res. .

Abstract

With nearly 42 million mild traumatic brain injuries (mTBIs) occurring worldwide every year, understanding the factors that may adversely influence recovery after mTBI is important for developing guidelines in mTBI management. Extensive clinical evidence exists documenting the detrimental effects of elevated temperature levels on recovery after moderate to severe TBI. However, whether elevated temperature alters recovery after mTBI or concussion is an active area of investigation. Individuals engaged in exercise and competitive sports regularly experience body and brain temperature increases to hyperthermic levels and these temperature increases are prolonged in hot and humid ambient environments. Thus, there is a strong potential for hyperthermia to alter recovery after mTBI in a subset of individuals at risk for mTBI. Preclinical mTBI studies have found that elevating brain temperature to 39°C before mTBI significantly increases neuronal death within the cortex and hippocampus and also worsens cognitive deficits. This review summarizes the pathology and behavioral problems of mTBI that are exacerbated by hyperthermia and discusses whether hyperthermia is a variable that should be considered after concussion and mTBI. Finally, underlying pathophysiological mechanisms responsible for hyperthermia-induced altered responses to mTBI and potential gender considerations are discussed.

Keywords: concussion; fluid-percussion brain injury; hyperthermia; hypothermia; temperature; traumatic brain injury.

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Conflict of interest statement

No competing interests were disclosed.No competing interests were disclosed.No competing interests were disclosed.

Figures

Figure 1.
Figure 1.. Temperature responses during cycling.
Jugular venous blood temperature most closely reflects brain tissue temperature and is still elevated at 60 minutes during recovery (arrow). Figure reproduced with permission .
Figure 2.
Figure 2.. Exacerbation of cortical contusion volume with hyperthermia after mild traumatic brain injury (TBI) in an experimental model of TBI in rats.
Animals received mild fluid-percussion brain injury while ( a) normothermic (37°C), ( b) hyperthermic (39°C) beginning 15 minutes prior to mild TBI and for 2 hours after injury, or ( c) hyperthermic (39°C) only for 2 hours after injury. ( d) Brains were sectioned and stained with hematoxylin and eosin to visualize and quantify cortical contusion volume. Scale bars = 300 µm. * P <0.05 versus normothermic, # P <0.05 versus hyperthermic post only. Adapted from .
Figure 3.
Figure 3.. Increased hippocampal cell loss after mild traumatic brain injury (TBI) and mild hyperthermia.
Animals received ( a) sham surgery, mild fluid-percussion brain injury while ( b) normothermic (37°C), ( c) hyperthermic (39°C) beginning 15 minutes prior to mild TBI and for 2 hours after injury, or ( d) hyperthermic (39°C) only for 2 hours after injury. ( e) Neuronal loss in the dentate hilus was quantified by stereology in NeuN-immunostained sections. Scale bars = 300 µm. *** P <0.001 versus Sham, # P <0.05, ## P <0.001 versus normothermic. Adapted from .
Figure 4.
Figure 4.. Effects of temperature manipulations on cognitive outcome after mild traumatic brain injury (mTBI).
Animals received mild fluid-percussion brain injury while normothermic (37°C, mTBI+Normo) or hyperthermic (39°C, mTBI+Hyper). Cognition was assessed at 2–3 weeks post-injury and compared with non-injured, sham animals. ( a) Contextual fear conditioning was unaffected by mTBI but impaired in hyperthermic mTBI animals. ( b) Water maze performance on the probe trial to assess retention of spatial learning. Time spent in the trained quadrant was significantly decreased in hyperthermic mTBI animals as compared with sham animals. Figure reproduced with permission .

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