Mild Hyperthermia Worsens the Neuropathological Damage Associated with Mild Traumatic Brain Injury in Rats

Sakurai, Atsushi; Atkins, Coleen M.; Alonso, Ofelia F.; Bramlett, Helen M.; Dietrich, W. Dalton

doi:10.1089/neu.2011.2152

Cited by 50 publications

(46 citation statements)

References 81 publications

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“…To determine if hyperthermia in combination with a mTBI worsens cognitive recovery, we utilized the parasagittal fluid-percussion injury (FPI) model in adult male Sprague Dawley rats ( n =61, 2–4 mos, Charles Rivers Laboratories, Wilmington, MA, USA). Animals were anesthetized (70% nitrous oxide, 1–3% isoflurane, and 30% oxygen) 24 h prior to injury and surgically prepared for FPI as previously described (Sakurai et al, 2012; Titus et al, 2013). Briefly, anesthesia was induced with 3% isoflurane, 70% nitrous oxide and 30% oxygen, and animals were maintained at 1–2% isoflurane, 70% nitrous oxide and 30% oxygen.…”

Section: Methodsmentioning

confidence: 99%

“…Thus, in individuals that are engaged in strenuous activities including exercise, competitive sports or under highly stressful conditions, core temperatures may reach mildly hyperthermic levels that could potentially alter traumatic consequences. In a recent study, our laboratory first reported that artificially elevating brain temperature to 39 °C before mTBI significantly increased patterns of neuronal death within cortical and subcortical regions as compared to normothermic mTBI (Sakurai et al, 2012). …”

Section: Introductionmentioning

confidence: 99%

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Emergence of cognitive deficits after mild traumatic brain injury due to hyperthermia

Titus

Furones

Atkins

et al. 2015

Experimental Neurology

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Mild elevations in core temperature can occur in individuals involved in strenuous activities that are risky for potentially sustaining a mild traumatic brain injury (mTBI) or concussion. Recently, we have discovered that mild elevations in brain temperature can significantly aggravate the histopathological consequences of mTBI. However, whether this exacerbation of brain pathology translates into behavioral deficits is unknown. Therefore, we investigated the behavioral consequences of elevating brain temperature to mildly hyperthermic levels prior to mTBI. Adult male Sprague Dawley rats underwent mild fluid-percussion brain injury or sham surgery while normothermic (37 °C) or hyperthermic (39 °C) and were allowed to recover for 7 days. Animals were then assessed for cognition using the water maze and cue and contextual fear conditioning. We found that mTBI alone at normothermia had no effect on long-term cognitive measures whereas mTBI animals that were hyperthermic for 15 min prior to and for 4 h after brain injury were significantly impaired on long-term retention for both the water maze and fear conditioning. In contrast, hyperthermic mTBI animals cooled within 15 min to normothermia demonstrated no significant long-term cognitive deficits. Mild TBI irrespective of temperature manipulations resulted in significant short-term working memory deficits. Cortical atrophy and contusions were detected in all mTBI treatment groups and contusion volume was significantly less in hyperthermic mTBI animals that were cooled as compared to hyperthermic mTBI animals that remained hyperthermic. These results indicate that brain temperature is an important variable for mTBI outcome and that mildly elevated temperatures at the time of injury result in persistent cognitive deficits. Importantly, cooling to normothermia after mTBI prevents the development of long-term cognitive deficits caused by hyperthermia. Reducing temperature to normothermic levels soon after mTBI represents a rational approach to potentially mitigate the long-term consequences of mTBI.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Emergence of cognitive deficits after mild traumatic brain injury due to hyperthermia

Titus

Furones

Atkins

et al. 2015

Experimental Neurology

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“…However, limited information is available regarding the potential consequences of secondary hyperthermia on outcomes following mild TBI. Fortunately, recent research by Sakurai et al [72] combined mild FPI with PTH in rats. Elevation in brain temperature after mild TBI was apparently shown to aggravate pathological damage.…”

Section: Experimental Model Of Tbi Complicated By Hyperthermiamentioning

confidence: 99%

Where are we in the modelling of traumatic brain injury? Models complicated by secondary brain insults

et al. 2014

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A more complete understanding of the interactions between the injured brain and secondary insults represents a potentially fruitful avenue that may increase the likelihood of developing effective therapies. Experimental models of TBI should not only attempt to model the focal or diffuse changes resulting from external forces, but also integrate, when appropriate, secondary insults reminiscent of human situations.

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“…15 To our knowledge, however, they have not been described following mild TBI within the context of exercise. Here we describe the HR, CBT, and ambulatory activity during exercise regimens that elicit a low or high stress response.…”

Section: Introductionmentioning

confidence: 96%

“…A recent study utilizing an experimental mild TBI demonstrated that peritraumatic mild hyperthermia increased cortical contusion size. 15 …”

mentioning

confidence: 99%

Temperature and Heart Rate Responses to Exercise following Mild Traumatic Brain Injury

Griesbach

Tio

Nair

et al. 2013

Journal of Neurotrauma

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We have previously reported that mild fluid percussion injury (FPI) is associated with a heightening of the hypothalamic-pituitary-adrenal axis response during the first post-injury weeks. This is the same time period when rehabilitative exercise has been strongly suggested to be ineffective. Here, we explored whether cardiac and temperature autonomic function may also be compromised during this early post-injury period. Following an FPI or sham injury, rats were exercised with forced (fRW) or voluntary (vRW) running wheels on post-injury days 0-4 and 7-11. Results indicated that overall activity levels were decreased and circadian rhythm was affected after FPI. Autonomic disruptions became evident when exercise was introduced, and these disruptions were dependent upon the characteristics of exercise. Elevations in heart rate (HR) and core body temperature (CBT) were observed as a response to vRW and fRW. FPI animals had more pronounced increases in HR as a result of vRW. Likewise, increases in HR were observed with fRW in all animals. A strong stress response has recently been associated with fRW exercise. FPI rats exposed to fRW were more responsive to experimental manipulations and had higher a CBT after the FRW session. The results suggest that subacute exercise, particularly if linked to a strong stress response, may be counterproductive. Here we show that cardiac and temperature autonomic function are compromised during the subacute period following a mild TBI.

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Mild Hyperthermia Worsens the Neuropathological Damage Associated with Mild Traumatic Brain Injury in Rats

Cited by 50 publications

References 81 publications

Emergence of cognitive deficits after mild traumatic brain injury due to hyperthermia

Emergence of cognitive deficits after mild traumatic brain injury due to hyperthermia

Where are we in the modelling of traumatic brain injury? Models complicated by secondary brain insults

Temperature and Heart Rate Responses to Exercise following Mild Traumatic Brain Injury

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