Journal of neurotrauma
-
Journal of neurotrauma · Sep 2018
Comparative StudyA Comparison of Oxidative Lactate Metabolism in Traumatically Injured Brain and Control Brain.
Metabolic abnormalities occur after traumatic brain injury (TBI). Glucose is conventionally regarded as the major energy substrate, although lactate can also be an energy source. We compared 3-13C lactate metabolism in TBI with "normal" control brain and muscle, measuring 13C-glutamine enrichment to assess tricarboxylic acid (TCA) cycle metabolism. ⋯ In TBI, with 3-13C lactate perfusion, microdialysate glucose concentration increased nonsignificantly (mean +11.9%, p = 0.463), with significant increases (p = 0.028) for lactate (+174%), pyruvate (+35.8%), and lactate/pyruvate ratio (+101.8%). Microdialysate 13C-glutamine fractional enrichments (median, interquartile range) were: for C4 5.1 (0-11.1) % in TBI and 5.7 (4.6-6.8) % in control brain, for C3 0 (0-5.0) % in TBI and 0 (0-0) % in control brain, and for C2 2.9 (0-5.7) % in TBI and 1.8 (0-3.4) % in control brain. 13C-enrichments were not statistically different between TBI and control brain, showing both metabolize 3-13C lactate via TCA cycle, in contrast to muscle. Several patients with TBI exhibited 13C-glutamine enrichment above the non-TBI control range, suggesting lactate oxidative metabolism as a TBI "emergency option."
-
Journal of neurotrauma · Sep 2018
Long-Term Functional and Structural Consequences of Primary Blast Overpressure to the Eye.
Acoustic blast overpressure (ABO) injury in military personnel and civilians is often accompanied by delayed visual deficits. However, most animal model studies dealing with blast-induced visual defects have focused on short-term (≤1 month) changes. Here, we evaluated long-term (≤8 months) retinal structure and function deficits in rats with ABO injury. ⋯ Age, but not blast exposure, altered Y-maze outcomes. GFAP was greatly increased in blast-exposed retinas. ABO exposure resulted in visual and retinal changes that persisted up to 8 months post-blast, mimicking some of the visual deficits observed in human blast-exposed patients, thereby making this a useful model to study mechanisms of injury and potential treatments.
-
Journal of neurotrauma · Sep 2018
Traumatic Brain Injury-Induced Acute Lung Injury: Evidence for Activation and Inhibition of a Neural-Respiratory-Inflammasome Axis.
Approximately 20-25% of traumatic brain injury (TBI) subjects develop acute lung injury (ALI), but the pathomechanisms of TBI-induced ALI remain poorly defined. Our previous work has shown that the inflammasome plays a critical role in TBI-induced secondary pathophysiology and that inflammasome proteins are released in extracellular vesicles (EV) after TBI. Here we investigated whether EV-mediated inflammasome signaling contributed to the etiology of TBI-induced ALI. ⋯ We show that TBI releases EV containing inflammasome proteins into serum that target the lung to cause ALI, supporting activation of a neural-respiratory-inflammasome axis. Administration of a low-molecular-weight heparin (enoxaparin, a blocker of EV uptake) or treatment with a monoclonal antibody against apoptosis speck-like staining protein containing a caspase recruitment domain (anti-ASC) after adoptive transfer of EV isolated from TBI-injured mice significantly inhibited inflammasome activation in the lungs of recipient mice resulting in improved ALI scores. This axis constitutes an important arm of the innate inflammatory response in lung pathology after TBI and targeting this axis represents a novel therapeutic treatment for TBI-induced ALI.
-
Journal of neurotrauma · Sep 2018
Memory Deficit in an Object Location Task after Mild Traumatic Brain Injury Is Associated with Impaired Early Object Exploration and Both Are Restored by Branched Chain Amino Acid Dietary Therapy.
The relation between traumatic brain injury (TBI) and memory dysfunction is well established, yet imprecise. Here, we investigate whether mild TBI causes a specific deficit in spatial episodic memory. Fifty-eight (29 TBI, 29 sham) mice were run in a spatial recognition task. ⋯ In addition, the TBI-specific impairment was accompanied by a decrease in exploratory behavior during the first 3 mins of the initial exposure to the test objects. These memory and exploratory behavioral deficits were linked as branched-chain amino acid (BCAA) dietary therapy restored both memory performance and normal exploratory behavior. Our findings 1) support the use of BCAA therapy as a potential treatment for mild TBI and 2) suggest that poor memory performance post-TBI is associated with a deficit in exploratory behavior that is likely to underlie the encoding needed for memory formation.
-
Journal of neurotrauma · Sep 2018
Imagining the Future in Children with Severe Traumatic Brain Injury.
Imagining future events is thought to rely on recombination and integration of past episodic memory traces into future events. Future and past events contain episodic and nonepisodic details. Children with severe traumatic brain injury (TBI) were found to have impaired recall of past episodic (but not semantic) event details. ⋯ The groups did not differ on ratings of visual intensity and rehearsal. Our study has shown that children who have sustained severe TBI had impoverished recall of past, but not generation of future, events. This unexpected dissociation between past and future event construction requires further research.