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Exposure to explosive shockwave often leads to blast-induced traumatic brain injury in military and civilian populations. Unprotected ears are most often damaged following exposure to blasts. Although there is an association between tympanic membrane perforation and TBI in blast exposure victims, little is known about how and to what extent blast energy is transmitted to the central nervous system via the external ear canal. The present study investigated whether exposure to blasts directed through the ear canal causes brain injury in Long-Evans rats. GPR84 antagonist 8 price Animals were exposed to a single blast (0-30 pounds per square inch (psi)) through the ear canal, and brain injury was evaluated by histological and behavioral outcomes at multiple time-points. Blast exposure not only caused tympanic membrane perforation but also produced substantial neuropathological changes in the brain, including increased expression of c-Fos, induction of a profound chronic neuroinflammatory response, and apoptosis of neurons. The blast-induced injury was not limited only to the brainstem most proximal to the source of the blast, but also affected the forebrain including the hippocampus, amygdala and the habenula, which are all involved in cognitive functions. Indeed, the animals exhibited long-term neurological deficits, including signs of anxiety in open field tests 2 months following blast exposure, and impaired learning and memory in an 8-arm maze 12 months following blast exposure. These results suggest that the unprotected ear canal provides a locus for blast waves to cause TBI. This study was approved by the Institutional Animal Care and Use Committee at the University of Mississippi Medical Center (Animal protocol# 0932E, approval date September 30, 2016 and 0932F, approval date September 27, 2019).A chronic phase following repetitive mild traumatic brain injury can present as chronic traumatic encephalopathy in some cases, which requires a neuropathological examination to make a definitive diagnosis. Positron emission tomography (PET) is a molecular imaging modality that has high sensitivity for detecting even very small molecular changes, and can be used to quantitatively measure a range of molecular biological processes in the brain using different radioactive tracers. Functional changes have also been reported in patients with different forms of traumatic brain injury, especially mild traumatic brain injury and subsequent chronic traumatic encephalopathy. Thus, PET provides a novel approach for the further evaluation of mild traumatic brain injury at molecular levels. In this review, we discuss the recent advances in PET imaging with different radiotracers, including radioligands for PET imaging of glucose metabolism, tau, amyloid-beta, γ-aminobutyric acid type A receptors, and neuroinflammation, in the identification of altered neurological function. These novel radiolabeled ligands are likely to have widespread clinical application, and may be helpful for the treatment of mild traumatic brain injury. Moreover, PET functional imaging with different ligands can be used in the future to perform large-scale and sequential studies exploring the time-dependent changes that occur in mild traumatic brain injury.Amyotrophic lateral sclerosis is a fatal neurodegenerative disease characterized by progressive muscle wasting, breathing and swallowing difficulties resulting in patient's death in two to five years after disease onset. In amyotrophic lateral sclerosis, both upper and lower motor neurons of the corticospinal tracts are involved in the process of neurodegeneration, accounting for great clinical heterogeneity of the disease. Clinical phenotype has great impact on the pattern and rate of amyotrophic lateral sclerosis progression and overall survival prognosis. Creating more homogenous patient groups in order to study the effects of drug agents on specific manifestations of the disease is a challenging issue in amyotrophic lateral sclerosis clinical trials. Since amyotrophic lateral sclerosis has low incidence rates, conduction of multicenter trials requires certain standardized approaches to disease diagnosis and staging. This review focuses on the current approaches in amyotrophic lateral sclerosis classification and staging system based on clinical examination and additional instrumental methods, highlighting the role of upper and lower motor neuron involvement in different phenotypes of the disease. We demonstrate that both clinical and instrumental findings can be useful in evaluating severity of upper motor neuron and lower motor neuron involvement and predicting the following course of the disease. Addressing disease heterogeneity in amyotrophic lateral sclerosis clinical trials could lead to study designs that will assess drug efficacy in specific patient groups, based on the disease pathophysiology and spatiotemporal pattern. Although clinical evaluation can be a sufficient screening method for dividing amyotrophic lateral sclerosis patients into clinical subgroups, we provide proof that instrumental studies could provide valuable insights in the disease pathology.Phantom limb pain is a chronic pain syndrome that is difficult to cope with. Despite neurostimulation treatment is indicated for refractory neuropathic pain, there is scant evidence from randomized controlled trials to recommend it as the treatment choice. Thus, a systematic review was performed to analyze the efficacy of central nervous system stimulation therapies as a strategy for pain management in patients with phantom limb pain. A literature search for studies conducted between 1970 and September 2020 was carried out using the MEDLINE and Embase databases. Principles of The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline were followed. There were a total of 10 full-text articles retrieved and included in this review. Deep brain stimulation, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and motor cortex stimulation were the treatment strategies used in the selected clinical trials. Repetitive transcranial magnetic stimulation and transcranial direct current stimulation were effective therapies to reduce pain perception, as well as to relieve anxiety and depression symptoms in phantom limb pain patients.
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