PMID- 32502571 OWN - NLM STAT- MEDLINE DCOM- 20210514 LR - 20210514 IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 441 DP - 2020 Aug 10 TI - Gravitational Transitions Increase Posterior Cerebral Perfusion and Systemic Oxidative-nitrosative Stress: Implications for Neurovascular Unit Integrity. PG - 142-160 LID - S0306-4522(20)30350-X [pii] LID - 10.1016/j.neuroscience.2020.05.048 [doi] AB - The present study examined if repeated bouts of micro- and hypergravity during parabolic flight (PF) alter structural integrity of the neurovascular unit (NVU) subsequent to free radical-mediated changes in regional cerebral perfusion. Six participants (5male symbol, 1female symbol) aged 29 +/- 11 years were examined before, during and after a 3 h PF and compared to six sex and age-matched (27 +/- 6 years) normogravity controls. Blood flow was measured in the anterior (middle cerebral artery, MCA; internal carotid artery, ICA) and posterior (vertebral artery, VA) circulation (duplex ultrasound) in-flight over the course of 15 parabolas. Venous blood was assayed for free radicals (electron paramagnetic resonance spectroscopy), nitric oxide (NO, ozone-based chemiluminescence) and NVU integrity (chemiluminescence/ELISA) in normogravity before and after exposure to 31 parabolas. While MCA velocity did not change (P > 0.05), a selective increase in VA flow was observed during the most marked gravitational transition from micro- to hypergravity (P < 0.05). Increased oxidative-nitrosative stress defined by a free radical-mediated reduction in NO and elevations in glio-vascular GFAP and S100ss were observed after PF (P < 0.05), the latter proportional to the increase in VA flow (r = 0.908, P < 0.05). In contrast, biomarkers of neuronal-axonal damage (neuron-specific enolase, neurofilament light-chain, ubiquitin carboxy-terminal hydrolase L1 and tau) did not change (P > 0.05). Collectively, these findings suggest that the cumulative effects of repeated gravitational transitions may promote minor blood-brain barrier disruption, potentially related to the combined effects of haemodynamic (posterior cerebral hyperperfusion) and molecular (systemic oxidative-nitrosative) stress. CI - Copyright (c) 2020 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Bailey, Damian M AU - Bailey DM AD - Neurovascular Research Laboratory, Faculty of Life Sciences and Education, University of South Wales, Glamorgan, UK. Electronic address: damian.bailey@southwales.ac.uk. FAU - Laneelle, Damien AU - Laneelle D AD - Service de Medecine Vasculaire, Centre Hospitalo-Universitaire, Caen, France; UNICAEN, INSERM, COMETE, GIP CYCERON, Normandie University, Caen, France. FAU - Trihan, Jean-Eudes AU - Trihan JE AD - Service de Medecine Vasculaire, Centre Hospitalier Universitaire de Poitiers, Poitiers, France. FAU - Marchi, Nicola AU - Marchi N AD - UMR, Laboratory of Cerebrovascular and Glia Research, Department of Neuroscience, Institute of Functional Genomics (CNRS Unit Mixte de Recherche 5203; INSERM U1191), University of Montpellier, France. FAU - Stacey, Benjamin S AU - Stacey BS AD - Neurovascular Research Laboratory, Faculty of Life Sciences and Education, University of South Wales, Glamorgan, UK. FAU - Tamiya, Kazuki AU - Tamiya K AD - Department of Biomedical Engineering, Toyo University, Kawagoe-Shi, Saitama, Japan. FAU - Washio, Takuro AU - Washio T AD - Department of Biomedical Engineering, Toyo University, Kawagoe-Shi, Saitama, Japan. FAU - Tuaillon, Edouard AU - Tuaillon E AD - Unit Mixte de Recherche, INSERM l'Etablissement Francais du Sang, University of Montpellier 1, Montpellier, France. FAU - Hirtz, Christophe AU - Hirtz C AD - LBPC-PPC, University of Montpellier, Institute of Regenerative Medicine-Biotherapy IRMB, Centre Hospitalier Universitaire de Montpellier, INSERM, Montpellier, France. FAU - Lehmann, Sylvain AU - Lehmann S AD - LBPC-PPC, University of Montpellier, Institute of Regenerative Medicine-Biotherapy IRMB, Centre Hospitalier Universitaire de Montpellier, INSERM, Montpellier, France. FAU - Ogoh, Shigehiko AU - Ogoh S AD - Neurovascular Research Laboratory, Faculty of Life Sciences and Education, University of South Wales, Glamorgan, UK; Department of Biomedical Engineering, Toyo University, Kawagoe-Shi, Saitama, Japan. FAU - Normand, Herve AU - Normand H AD - UNICAEN, INSERM, COMETE, GIP CYCERON, Normandie University, Caen, France; UNICAEN, COMETE, Caen, France; INSERM, U 1075 COMETE, Caen, France; Department of Clinical Physiology, Centre Hospitalier Universitaire de Caen, Caen, France. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200602 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Free Radicals) SB - IM MH - Adolescent MH - Adult MH - *Cerebrovascular Circulation MH - Free Radicals MH - Humans MH - Middle Cerebral Artery MH - *Nitrosative Stress MH - Oxidative Stress MH - Young Adult OTO - NOTNLM OT - blood-brain barrier OT - cerebral blood flow OT - free radicals OT - gravity OT - nitric oxide EDAT- 2020/06/06 06:00 MHDA- 2021/05/15 06:00 CRDT- 2020/06/06 06:00 PHST- 2020/02/15 00:00 [received] PHST- 2020/05/22 00:00 [revised] PHST- 2020/05/26 00:00 [accepted] PHST- 2020/06/06 06:00 [pubmed] PHST- 2021/05/15 06:00 [medline] PHST- 2020/06/06 06:00 [entrez] AID - S0306-4522(20)30350-X [pii] AID - 10.1016/j.neuroscience.2020.05.048 [doi] PST - ppublish SO - Neuroscience. 2020 Aug 10;441:142-160. doi: 10.1016/j.neuroscience.2020.05.048. Epub 2020 Jun 2.