PMID- 38256223 OWN - NLM STAT- MEDLINE DCOM- 20240124 LR - 20240201 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 25 IP - 2 DP - 2024 Jan 17 TI - The Neurovascular Unit as a Locus of Injury in Low-Level Blast-Induced Neurotrauma. LID - 10.3390/ijms25021150 [doi] LID - 1150 AB - Blast-induced neurotrauma has received much attention over the past decade. Vascular injury occurs early following blast exposure. Indeed, in animal models that approximate human mild traumatic brain injury or subclinical blast exposure, vascular pathology can occur in the presence of a normal neuropil, suggesting that the vasculature is particularly vulnerable. Brain endothelial cells and their supporting glial and neuronal elements constitute a neurovascular unit (NVU). Blast injury disrupts gliovascular and neurovascular connections in addition to damaging endothelial cells, basal laminae, smooth muscle cells, and pericytes as well as causing extracellular matrix reorganization. Perivascular pathology becomes associated with phospho-tau accumulation and chronic perivascular inflammation. Disruption of the NVU should impact activity-dependent regulation of cerebral blood flow, blood-brain barrier permeability, and glymphatic flow. Here, we review work in an animal model of low-level blast injury that we have been studying for over a decade. We review work supporting the NVU as a locus of low-level blast injury. We integrate our findings with those from other laboratories studying similar models that collectively suggest that damage to astrocytes and other perivascular cells as well as chronic immune activation play a role in the persistent neurobehavioral changes that follow blast injury. FAU - Elder, Gregory A AU - Elder GA AD - Neurology Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA. AD - Department of Neurology, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY 10029, USA. AD - Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY 10029, USA. AD - Mount Sinai Alzheimer's Disease Research Center and the Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. FAU - Gama Sosa, Miguel A AU - Gama Sosa MA AD - Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY 10029, USA. AD - General Medical Research Service, James J. Peters Department of Veterans Affairs Medical Center, Bronx, NY 10468, USA. FAU - De Gasperi, Rita AU - De Gasperi R AD - Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY 10029, USA. AD - Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA. FAU - Perez Garcia, Georgina AU - Perez Garcia G AD - Department of Neurology, Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY 10029, USA. AD - Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA. FAU - Perez, Gissel M AU - Perez GM AD - Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA. FAU - Abutarboush, Rania AU - Abutarboush R AD - Department of Neurotrauma, Operational and Undersea Medicine Directorate, Naval Medical ResearchCommand, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. AD - The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA. FAU - Kawoos, Usmah AU - Kawoos U AD - Department of Neurotrauma, Operational and Undersea Medicine Directorate, Naval Medical ResearchCommand, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. AD - The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD 20817, USA. FAU - Zhu, Carolyn W AU - Zhu CW AD - Mount Sinai Alzheimer's Disease Research Center and the Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. AD - Research and Development Service, James J. Peters Department of Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA. AD - Department of Geriatrics and Palliative Care, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. FAU - Janssen, William G M AU - Janssen WGM AD - Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. AD - Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. FAU - Stone, James R AU - Stone JR AD - Department of Radiology and Medical Imaging, University of Virginia, 480 Ray C Hunt Drive, Charlottesville, VA 22903, USA. FAU - Hof, Patrick R AU - Hof PR AUID- ORCID: 0000-0002-3208-1154 AD - Mount Sinai Alzheimer's Disease Research Center and the Ronald M. Loeb Center for Alzheimer's Disease, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. AD - Department of Geriatrics and Palliative Care, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. AD - Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. AD - Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. FAU - Cook, David G AU - Cook DG AD - Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, 1660 S Columbian Way, Seattle, WA 98108, USA. AD - Department of Medicine, University of Washington, 1959 NE Pacific St., Seattle, WA 98195, USA. FAU - Ahlers, Stephen T AU - Ahlers ST AD - Department of Neurotrauma, Operational and Undersea Medicine Directorate, Naval Medical ResearchCommand, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. LA - eng GR - I01 BX005882/BX/BLRD VA/United States GR - I01 BX002311/BX/BLRD VA/United States GR - I01 BX004067/BX/BLRD VA/United States GR - I01 RX002660/RX/RRD VA/United States GR - P30 AG066514/AG/NIA NIH HHS/United States GR - I01 RX003846/RX/RRD VA/United States PT - Journal Article PT - Review DEP - 20240117 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 SB - IM MH - Animals MH - Humans MH - *Blast Injuries MH - Endothelial Cells MH - *Brain Concussion MH - *Vascular System Injuries MH - Astrocytes MH - Inflammation PMC - PMC10816929 OTO - NOTNLM OT - animal models OT - astrocytes OT - blast OT - inflammation OT - traumatic brain injury OT - vascular pathology COIS- The authors declare no conflicts of interest. EDAT- 2024/01/23 06:43 MHDA- 2024/01/24 06:42 PMCR- 2024/01/17 CRDT- 2024/01/23 01:13 PHST- 2023/12/12 00:00 [received] PHST- 2024/01/11 00:00 [revised] PHST- 2024/01/11 00:00 [accepted] PHST- 2024/01/24 06:42 [medline] PHST- 2024/01/23 06:43 [pubmed] PHST- 2024/01/23 01:13 [entrez] PHST- 2024/01/17 00:00 [pmc-release] AID - ijms25021150 [pii] AID - ijms-25-01150 [pii] AID - 10.3390/ijms25021150 [doi] PST - epublish SO - Int J Mol Sci. 2024 Jan 17;25(2):1150. doi: 10.3390/ijms25021150.