Mild Hyperthermia Aggravates Glucose Metabolic Consequences in Repetitive Concussion

Meghan Blaya,Helen Bramlett,Jessie Truettner,William Dalton Dietrich,Weizhao Zhao

doi:10.3390/ijms21020609

Abstract

Traumatic brain injury (TBI) is one of the leading causes of mortality and disability around the world. Mild TBI (mTBI) makes up approximately 80% of reported cases and often results in transient psychological abnormalities and cognitive disruption. At-risk populations for mTBI include athletes and other active individuals who may sustain repetitive concussive injury during periods of exercise and exertion when core temperatures are elevated. Previous studies have emphasized the impact that increased brain temperature has on adverse neurological outcomes. A lack of diagnostic tools to assess concussive mTBI limits the ability to effectively identify the post-concussive period during which the brain is uniquely susceptible to damage upon sustaining additional injury. Studies have suggested that a temporal window of increased vulnerability that exists corresponds to a period of injury-induced depression of cerebral glucose metabolism. In the current study, we sought to evaluate the relationship between repetitive concussion, local cerebral glucose metabolism, and brain temperature using the Marmarou weight drop model to generate mTBI. Animals were injured three consecutive times over a period of 7 days while exposed to either normothermic or hyperthermic temperatures for 15 min prior to and 1 h post each injury. A 14C-2-deoxy-d-glucose (2DG) autoradiography was used to measure local cerebral metabolic rate of glucose (lCMRGlc) in 10 diverse brain regions across nine bregma levels 8 days after the initial insult. We found that repetitive mTBI significantly decreased glucose utilization bilaterally in several cortical areas, such as the cingulate, visual, motor, and retrosplenial cortices, as well as in subcortical areas, including the caudate putamen and striatum, compared to sham control animals. lCMRGlc was significant in both normothermic and hyperthermic repetitive mTBI animals relative to the sham group, but to a greater degree when exposed to hyperthermic conditions. Taken together, we report significant injury-induced glucose hypometabolism after repetitive concussion in the brain, and additionally highlight the importance of temperature management in the acute period after brain injury.

Highlights

Traumatic brain injury (TBI), once referred to as the “silent epidemic”, is well recognized as a critical public health and socioeconomic problem
We found that hyperthermia exposure at each mild TBI (mTBI) showed an even greater degree of glucose hypometabolism with all nine bregma levels exhibiting this pattern (Figure 1, Right)
We found that hyperthermia exposure at each mTBI showed an even greater degree of glucose hypometabolism with all nine bregma levels Ienxt.hJi.bMitoiln

Summary

Introduction

Traumatic brain injury (TBI), once referred to as the “silent epidemic”, is well recognized as a critical public health and socioeconomic problem. In 2013, approximately 2.8 million TBI-related emergency department visitations, hospitalizations, and deaths occurred in the United States [1]. This number likely underestimates the true number of TBIs due to individuals with mild TBI (mTBI) not seeking medical care or being treated in outpatient or non-civilian facilities [2]. MTBI makes up approximately 80% of reported cases and is commonly referred to as concussion [3]. Clinical studies have shown that 10–40% of patients will go on to develop post-concussion syndrome [5,6]. Some patients may acquire neuropsychiatric comorbidities, such as posttraumatic stress disorder, in the chronic period after the insult [8]

Methods

Results

Conclusion