Neuron‐derived exosomes (NDEs) were enriched by anti‐L1CAM antibody immunoabsorption from plasmas of subjects ages 18–26 yr within 1 wk after a sports‐related mild traumatic brain injury (acute mTBI) (n = 18), 3 mo or longer after the last of 2–4 mTBIs (chronic mTBI) (n = 14) and with no recent history of TBI (controls) (n = 21). Plasma concentrations of NDEs, assessed by counts and levels of extracted exosome marker CD81, were significantly depressed by a mean of 45% in acute mTBI (P < 0.0001), but not chronic mTBI, compared with controls. Mean CD81‐normalized NDE levels of a range of functional brain proteins were significantly abnormal relative to those of controls in acute but not chronic mTBI, including ras‐related small GTPase 10, 73% decrease; annexin VII, 8.8‐fold increase; ubiquitin C‐terminal hydrolase L1, 2.5‐fold increase; AII spectrin fragments, 1.9‐fold increase; claudin‐5, 2.7‐fold increase; sodium‐potassium‐chloride cotransporter‐1, 2.8‐fold increase; aquaporin 4, 8.9‐fold increase (3.6‐fold increase in chronic mTBI); and synaptogyrin‐3, 3.1‐fold increase (1.3‐fold increase in chronic mTBI) (all acute mTBI proteins P < 0.0001). In chronic mTBI, there were elevated CD81‐normalized NDE levels of usually pathologic β‐amyloid peptide 1‐42 (1.6‐fold, P < 0.0001), P‐T181‐tau (2.2‐fold, P < 0.0001), P‐S396‐tau (1.6‐fold, P < 0.01), IL‐6 (16‐fold, P < 0.0001), and prion cellular protein (PRPc) (5.1‐fold, P < 0.0001) with lesser or greater (IL‐6, PRPc) increases in acute mTBI. Increases in NDE levels of most neurofunctional proteins in acute, but not chronic, mTBI, and elevations of most NDE neuropathological proteins in chronic and acute mTBI delineated phase‐specificity. Longitudinal studies of more mTBI subjects may identify biomarkers predictive of and etiologically involved in mTBI‐induced neurodegeneration.—Goetzl, E. J., Elahi, F. M., Mustapic, M., Kapogiannis, D., Pryhoda, M., Gilmore, A., Gorgens, K. A., Davidson, B., Granholm, A.‐C., Ledreux, A. Altered levels of plasma neuron‐derived exosomes and their cargo proteins characterize acute and chronic mild traumatic brain injury. FASEB J. 33, 5082–5088 (2019). http://www.fasebj.org
Possible involvement of complement (C) systems in the pathogenesis of traumatic brain injury (TBI) was investigated by quantifying Cproteins in plasma astrocytederived exosomes (ADEs) of subjects with sports-related TBI (sTBI) and TBI in military veterans (mtTBI) without cognitive impairment. All sTBI subjects (n = 24) had mild injuries, whereas eight of the mtTBI subjects had moderate, and 17 had mild injuries. Plasma levels of ADEs were decreased after acute sTBI and returned to normal within months. Cprotein levels in ADEs were from 12-to 35-fold higher than the corresponding levels in neuron-derived exosomes. CD81 exosome markernormalized ADE levels of classical pathway C4b, alternative pathway factor D and Bb, lectin pathway mannose-binding lectin (MBL), and shared neurotoxic effectors C3b and C5b-9 terminal C complex were significantly higher and those of C regulatory proteins CR1 and CD59 were lower in the first week of acute sTBI (n = 12) than in controls (n = 12). Most C abnormalities were no longer detected in chronic sTBI at 3-12 months after acute sTBI, except for elevated levels of factor D, Bb, and MBL. In contrast, significant elevations of ADE levels of C4b, factor D, Bb, MBL, C3b and C5b-9 terminal C complex, and depressions of CR1 and CD59 relative to those of controls were observed after 1-4 years in early chronic mtTBI (n = 10) and 3360 | GOETZL ET aL.How to cite this article: Goetzl EJ, Yaffe K, Peltz CB, et al. Traumatic brain injury increases plasma astrocytederived exosome levels of neurotoxic complement proteins.
An estimated 49.7 million people in the United States live with one or more disabilities, representing nearly 20% of the 257.2 million individuals ages 5 and older in the civilian population (U.S. Census Bureau, 2003). Most psychologists are likely to have the opportunity to work with clients who have disabilities (R. and need the competencies to provide ethical services to this growing proportion of the population. What constitutes ethical practice with people with disabilities? First, the ethical issues involved in providing services for people with disabilities are outlined, and 2 vignettes and a number of questions for practitioners and educators are presented. Then, 3 invited experts provide commentaries that address these issues, raise additional questions, and provide important resources.
Many psychologists play a central role in the training of master's-level counselors. However, with the strict Council for Accreditation of Counseling and Related Educational Programs (CACREP) accreditation rules for core faculty in counseling programs, the American Psychological Association is now entertaining a proposal to accredit training for master's-level counselors. In this article, we present our position on the need to continue to have interprofessional training for counselors and psychologists. Public Significance StatementMaster's-level training accreditation and licensure bodies could benefit from inclusive training, which promotes interprofessional educational practices. That is, professionals from allied mental health professions should be encouraged to train the next generation of counselors and psychologists.
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