PMID- 35012589 OWN - NLM STAT- MEDLINE DCOM- 20220303 LR - 20220303 IS - 2045-8118 (Electronic) IS - 2045-8118 (Linking) VI - 19 IP - 1 DP - 2022 Jan 10 TI - Chronic effects of blast injury on the microvasculature in a transgenic mouse model of Alzheimer's disease related Abeta amyloidosis. PG - 5 LID - 10.1186/s12987-021-00301-z [doi] LID - 5 AB - BACKGROUND: Altered cerebrovascular function and accumulation of amyloid-beta (Abeta) after traumatic brain injury (TBI) can contribute to chronic neuropathology and increase the risk for Alzheimer's disease (AD). TBI due to a blast-induced shock wave (bTBI) adversely affects the neurovascular unit (NVU) during the acute period after injury. However, the chronic effects of bTBI and Abeta on cellular components of the NVU and capillary network are not well understood. METHODS: We exposed young adult (age range: 76-106 days) female transgenic (Tg) APP/PS1 mice, a model of AD-like Abeta amyloidosis, and wild type (Wt) mice to a single bTBI (~ 138 kPa or ~ 20 psi) or to a Sham procedure. At 3-months or 12-months survival after exposure, we quantified neocortical Abeta load in Tg mice, and percent contact area between aquaporin-4 (AQP4)-immunoreactive astrocytic end-feet and brain capillaries, numbers of PDGFRbeta-immunoreactive pericytes, and capillary densities in both genotypes. RESULTS: The astroglia AQP4-capillary contact area in the Tg-bTBI group was significantly lower than in the Tg-Sham group at 3-months survival. No significant changes in the AQP4-capillary contact area were observed in the Tg-bTBI group at 12-months survival or in the Wt groups. Capillary density in the Tg-bTBI group at 12-months survival was significantly higher compared to the Tg-Sham control and to the Tg-bTBI 3-months survival group. The Wt-bTBI group had significantly lower capillary density and pericyte numbers at 12-months survival compared to 3-months survival. When pericytes were quantified relative to capillary density, no significant differences were detected among the experimental groups, for both genotypes. CONCLUSION: In conditions of high brain concentrations of human Abeta, bTBI exposure results in reduced AQP4 expression at the astroglia-microvascular interface, and in chronic capillary proliferation like what has been reported in AD. Long term microvascular changes after bTBI may contribute to the risk for developing chronic neurodegenerative disease later in life. CI - (c) 2022. The Author(s). FAU - Clark, Alexander T AU - Clark AT AD - Department of Neurology, University of Pittsburgh School of Medicine, 3471 Fifth Ave, Pittsburgh, PA, 15213, USA. FAU - Abrahamson, Eric E AU - Abrahamson EE AD - Geriatric Research Education and Clinical Center, VA Pittsburgh Healthcare System, University Drive C, Pittsburgh, PA, 15240, USA. AD - Department of Neurology, University of Pittsburgh School of Medicine, 3471 Fifth Ave, Pittsburgh, PA, 15213, USA. FAU - Harper, Matthew M AU - Harper MM AD - The Iowa City VA Center for the Prevention and Treatment of Visual Loss, 601 Hwy 6 West, Iowa City, IA, 52246, USA. AD - Department of Ophthalmology and Visual Sciences and Biology, University of Iowa, 200 Hawkins Dr, Iowa City, IA, 52242, USA. FAU - Ikonomovic, Milos D AU - Ikonomovic MD AD - Geriatric Research Education and Clinical Center, VA Pittsburgh Healthcare System, University Drive C, Pittsburgh, PA, 15240, USA. ikonomovicmd@upmc.edu. AD - Department of Neurology, University of Pittsburgh School of Medicine, 3471 Fifth Ave, Pittsburgh, PA, 15213, USA. ikonomovicmd@upmc.edu. AD - Department of Psychiatry, University of Pittsburgh School of Medicine, Thomas Detre Hall of the WPH, Room 1421, 3811 O'Hara Street, Pittsburgh, PA, 15213-2593, USA. ikonomovicmd@upmc.edu. LA - eng GR - 1I01RX000952/U.S. Department of Veterans Affairs/ GR - AG052528/AG/NIA NIH HHS/United States GR - T32MH019986/MH/NIMH NIH HHS/United States PT - Journal Article DEP - 20220110 PL - England TA - Fluids Barriers CNS JT - Fluids and barriers of the CNS JID - 101553157 RN - 0 (Amyloid beta-Peptides) SB - IM MH - *Alzheimer Disease/etiology/metabolism/physiopathology MH - Amyloid beta-Peptides/*metabolism MH - Animals MH - *Blast Injuries/complications/metabolism/physiopathology MH - *Brain Injuries, Traumatic/complications/metabolism/physiopathology MH - Disease Models, Animal MH - Female MH - Humans MH - Mice MH - Mice, Transgenic MH - *Microvessels/metabolism/physiopathology PMC - PMC8751260 OTO - NOTNLM OT - Alzheimer's disease OT - Amyloid OT - Astrocyte OT - Blast injury OT - Blood-brain barrier OT - NVU OT - Neurovascular unit OT - Pericyte OT - Traumatic brain injury COIS- The authors declare that they have no competing interests. EDAT- 2022/01/12 06:00 MHDA- 2022/03/04 06:00 PMCR- 2022/01/10 CRDT- 2022/01/11 05:54 PHST- 2021/11/03 00:00 [received] PHST- 2021/12/22 00:00 [accepted] PHST- 2022/01/11 05:54 [entrez] PHST- 2022/01/12 06:00 [pubmed] PHST- 2022/03/04 06:00 [medline] PHST- 2022/01/10 00:00 [pmc-release] AID - 10.1186/s12987-021-00301-z [pii] AID - 301 [pii] AID - 10.1186/s12987-021-00301-z [doi] PST - epublish SO - Fluids Barriers CNS. 2022 Jan 10;19(1):5. doi: 10.1186/s12987-021-00301-z.