Journal of neurotrauma
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Journal of neurotrauma · Jul 2019
Mild traumatic brain injury affects cognitive processing and modifies oscillatory brain activity during attentional tasks.
Despite the high prevalence of mild traumatic brain injury (mTBI), current diagnostic tools to objectively assess cognitive complaints after mTBI continue to be inadequate. Our aim was to identify neuronal correlates for cognitive difficulties in mTBI patients by evaluating the possible alterations in oscillatory brain activity during a behavioral task known to be sensitive to cognitive impairment after mTBI. We compared oscillatory brain activity during rest and cognitive tasks (Paced Auditory Serial Addition Test [PASAT] and a vigilance test [VT]) with magnetoencephalography between 25 mTBI patients and 20 healthy controls. ⋯ The ∼10-Hz (alpha) peak frequency declined in frontal, temporal, and parietal regions during PASAT compared with rest (p < 0.016) in patients, whereas in controls it remained the same or showed a tendency to increase. In patients, the ∼10-Hz peak amplitude was negatively correlated with behavioral performance in the Trail Making Test. The observed alterations in the cortical oscillatory activity during cognitive load may provide measurable neurophysiological correlates of cognitive difficulties in mTBI patients, even at the individual level.
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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
Plasma Tau and Amyloid Are Not Reliably Related to Injury Characteristics, Neuropsychological Performance, or White Matter Integrity in Service Members with a History of Traumatic Brain Injury.
The aim of this study was to examine the relationship between plasma tau and amyloid beta-42 (Aβ42), neuropsychological functioning, and white matter integrity in U. S. military service members with (n = 155) and without (n = 42) a history of uncomplicated mild (n = 83), complicated mild (n = 26), or moderate, severe, or penetrating (n = 46) traumatic brain injury (TBI). We hypothesized that higher levels of tau and Aβ42 would be related to reduced neurocognitive performance and white matter integrity. ⋯ In addition, there was no significant relationship between the biomarkers and age, education, sex, race, bodily injury severity, time since injury, TBI severity, or number of TBIs (all ps >0.15). Future investigation in larger samples of moderate, severe, and penetrating TBI are needed. Other plasma biomarkers, including phosphorylated tau, exosomal tau, and interleukin-10, may be more promising measures to use in the diagnosis, management, and treatment of TBI.
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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.