Journal of neurotrauma
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Journal of neurotrauma · Jul 2019
Prophylaxis pharmacotherapy to prevent the onset of post traumatic brain injury depression: a systematic review.
Depression is a common psychiatric problem following traumatic brain injury (TBI) with reported prevalence rates of 30-77% in the first year post-TBI. Given the negative influence of post-TBI depression on cognition and interpersonal, social, physical, and occupational functioning, early initiation of pharmacotherapy to prevent post-TBI depression has been considered. This systematic review will synthesize the available evidence from published studies on the effectiveness and harms of pharmacotherapy for the secondary prevention of post-TBI depression. ⋯ In the absence of tolerability data, existing data are insufficient to recommend sertraline prophylaxis. Optimal timing and treatment duration with identification of patients most likely to benefit from prophylaxis require further consideration. Dedicated prospective studies assessing the effects of beta-blockers and statins on post-TBI depression are required.
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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
In silico model of critical cerebral oxygenation after traumatic brain injury: Implications for rescuing hypoxic tissue.
Cerebral oxygen delivery is central to the modern intensive care of patients with severe traumatic brain injury. Low brain tissue oxygen tension (PbtO2) results from microvascular collapse and diffusion limitation and is associated with adverse outcome. A number of therapies to improve oxygen delivery are known to be effective in improving PbtO2. ⋯ We found that increasing cerebral blood flow/blood oxygen content or suppressing the cerebral metabolic rate were most effective at improving PbtO2 and reduced the hypoxic fraction. Within the limitations of our modeling assumptions, increasing the arterial oxygen partial pressure was less effective and only improved PbtO2 by creating a region of hyperoxic tissue with no improvement in hypoxic fraction. The in silico simulations can be useful in understanding the likely physiological effect of complex treatments for which measurement techniques do not exist.