Journal of neurotrauma
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Journal of neurotrauma · Jul 2019
Vergence Endurance Test: A Pilot Study for a Concussion Biomarker.
The Vergence Endurance Test (VET), a quantitative and objective eye movement assessment, was utilized to differentiate control from concussed subjects. Nine symptomatic concussed (2 male; 30.8 ± 11 years) and 9 asymptomatic control (6 male; 25.1 ± 1.4 years) subjects participated in the VET. Symmetrical disparity vergence step targets were presented with and without visual distractors. ⋯ For these parameters, the BAI and divergence response amplitude yielded the greatest accuracy, 78%, in their ability to discriminate between the groups. The VET objectively measures the change in vergence performance over time and shows promise as a method to diagnose a concussion. Future studies will determine whether the VET can be used to assess the extent of natural recovery and the effectiveness of therapeutic interventions.
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Journal of neurotrauma · Jul 2019
Glucose Dynamics of Cortical Spreading Depolarisation in Acute Brain Injury: A Systematic Review.
Cortical spreading depolarization (CSD) is an emerging mode of secondary neuronal damage in acute brain injury (ABI). Subsequent repolarisation is a metabolic process requiring glucose. Instances of CSD and glucose derangement are both linked to poor neurological outcome, but their causal inter-relationship is not fully defined. ⋯ These findings confirm a relationship between CSD and glucose, and suggest it may be cyclical, where CSD causes local glycopenia, which may potentiate further CSD. Positive observations were not common to all studies, likely due to differing methodology or heterogeneity in CSD propensity. Further study is required to delineate the utility of the clinical modulation of serum and cerebral glucose to alter the propensity for CSD following brain injury.
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Journal of neurotrauma · Jul 2019
Positive allosteric modulation of cholinergic receptors improves spatial learning following cortical contusion injury in mice.
We examined benzyl quinolone carboxylic acid (BQCA), a novel M1 muscarinic-positive allosteric modulator, for improving memory and motor dysfunction after cerebral cortical contusion injury (CCI). Adult mice received unilateral motorsensory cortical CCI or sham injury. Benzyl quinolone carboxylic acid (BQCA; 5, 10, and 20 mg/kg, intraperitoneally [i.p.] × 2/day × 3-4 weeks) or vehicle (Veh) were administered, and weekly evaluations were undertaken using a battery of motor tests, as well as the Morris water maze. ⋯ BQCA compared to vehicle-treated mice showed modest, though significantly increased, rCGU in motor regions, as well as a partial reversal of lesion-related rCGU findings in subregions of the hippocampal formation. rCGU in ipsilesional posterior CA1 demonstrated a significant inverse correlation with latency to find the submerged platform. BQCA at 20 mg/kg had no significant effect on general motor activity, body weight, or acute motor, secretory, or respiratory symptoms. Results suggest that BQCA is a candidate compound to improve learning and memory function after brain trauma and may not suffer the associated central nervous system side effects typically associated with even modest doses of other cholinergic enhancers.
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Journal of neurotrauma · Jul 2019
Deficiency of Plasminogen Activator Inhibitor Type 2 Limits Brain Edema Formation after Traumatic Brain Injury.
Plasminogen activator inhibitor-2 (PAI-2/SerpinB2) inhibits extracellular urokinase plasminogen activator (uPA). Under physiological conditions, PAI-2 is expressed at low levels but is rapidly induced by inflammatory triggers. It is a negative regulator of fibrinolysis and serves to stabilize clots. ⋯ Markers of vasogenic brain edema showed no difference in blood-brain barrier integrity and expression of blood-brain barrier proteins (claudin-5, zonula occludens-1). In contrast to plasminogen activator inhibitor-1 (PAI-1), PAI-2 plays a limited role for brain lesion formation and does not influence blood-brain barrier integrity. PAI-2 contributes to brain edema formation and could therefore be a promising new target to treat post-traumatic brain edema.
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Journal of neurotrauma · Jul 2019
Testosterone Administration after Traumatic Brain Injury Reduces Mitochondrial Dysfunction and Neurodegeneration.
Traumatic brain injury (TBI) increases Ca2+ influx into neurons and desynchronizes mitochondrial function leading to energy depletion and apoptosis. This process may be influenced by brain testosterone (TS) levels, which are known to decrease after TBI. We hypothesized that a TS-based therapy could preserve mitochondrial neuroenergetics after TBI, thereby reducing neurodegeneration. ⋯ At molecular level, TS prevented the increase in pTauSer396 and alpha-Spectrin fragmentation by the Ca2+dependent calpain-2 activation, and decreased both caspase-3 activation and Bax/BCL-2 ratio, which suggests a downregulation of mitochondrial apoptotic signals. Search Tool for the Retrieval of Interacting Genes/Proteins database provided two distinct gene/protein clusters, "upregulated and downregulated," interconnected through SOD2. Therefore, TS administration after a severe CCI improves the mitochondrial Ca2+extrusion through NCLX exchanger and ATP synthesis efficiency, ultimately downregulating the overexpression of molecular drivers of neurodegeneration.