PMID- 36675154
OWN - NLM
STAT- MEDLINE
DCOM- 20230124
LR  - 20230202
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 2
DP  - 2023 Jan 13
TI  - Ultrastructural Remodeling of the Blood-Brain Barrier and Neurovascular Unit by 
      Lipopolysaccharide-Induced Neuroinflammation.
LID - 10.3390/ijms24021640 [doi]
LID - 1640
AB  - The blood-brain barrier (BBB) is an interface primarily comprised of brain 
      endothelial cells (BECs), separating the central nervous system (CNS) from the 
      systemic circulation while carefully regulating the transport of molecules and 
      inflammatory cells, and maintaining the required steady-state environment. 
      Inflammation modulates many BBB functions, but the ultrastructural 
      cytoarchitectural changes of the BBB with inflammation are understudied. 
      Inflammation was induced in male 8-10-week-old CD-1 mice with intraperitoneal 
      lipopolysaccharide (LPS), using a regimen (3 mg/kg at 0, 6, and 24 h) that caused 
      robust BBB disruption but had minimal lethality at the study timepoint of 28 h. 
      Perfusion-fixed brains were collected and the frontal cortical layer III regions 
      were analyzed using a transmission electron microscopy (TEM). The LPS-treated 
      mice had pronounced ultrastructural remodeling changes in BECs that included 
      plasma membrane ruffling, increased numbers of extracellular microvesicles, small 
      exosome formation, aberrant BEC mitochondria, increased BEC transcytosis, while 
      tight junctions appeared to be unaltered. Aberrant pericytes were contracted with 
      rounded nuclei and a loss of their elongated cytoplasmic processes. Surveilling 
      microglial cells were attracted to the neurovascular unit (NVU) of BECs, and 
      astrocyte detachment and separation were associated with the formation of a 
      perivascular space and pericapillary edema. The LPS treatment resulted in 
      numerous ultrastructural aberrant remodeling changes to the neurovascular unit's 
      BECs, microglia, pericytes, and astrocytes. In summary, a disturbance of the NVU 
      morphology is a consequence of LPS treatment.
FAU - Erickson, Michelle A
AU  - Erickson MA
AUID- ORCID: 0000-0002-2575-1594
AD  - Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound 
      Health Care System, Seattle, WA 98108, USA.
AD  - Division of Gerontology and Geriatric Medicine, Department of Medicine, 
      University of Washington School of Medicine, Seattle, WA 98104, USA.
FAU - Shulyatnikova, Tatyana
AU  - Shulyatnikova T
AD  - Department of Pathological Anatomy and Forensic Medicine, Zaporizhzhia State 
      Medical University, Mayakovsky Avenue, 26, 69035 Zaporizhzhia, Ukraine.
FAU - Banks, William A
AU  - Banks WA
AD  - Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound 
      Health Care System, Seattle, WA 98108, USA.
AD  - Division of Gerontology and Geriatric Medicine, Department of Medicine, 
      University of Washington School of Medicine, Seattle, WA 98104, USA.
FAU - Hayden, Melvin R
AU  - Hayden MR
AUID- ORCID: 0000-0001-5178-4245
AD  - Department of Internal Medicine, Endocrinology Diabetes and Metabolism, Diabetes 
      and Cardiovascular Disease Center, University of Missouri School of Medicine, One 
      Hospital Drive, Columbia, MO 65211, USA.
LA  - eng
GR  - no number/This study was supported by the VA Puget Sound Healthcare System/
PT  - Journal Article
DEP - 20230113
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Lipopolysaccharides)
SB  - IM
MH  - Male
MH  - Mice
MH  - Animals
MH  - *Blood-Brain Barrier/metabolism
MH  - *Lipopolysaccharides/adverse effects
MH  - Neuroinflammatory Diseases
MH  - Endothelial Cells/metabolism
MH  - Astrocytes/metabolism
MH  - Inflammation/chemically induced/metabolism
PMC - PMC9862046
OTO - NOTNLM
OT  - blood-brain barrier
OT  - brain endothelial cells
OT  - caveolae-mediated vesicles
OT  - clathrin-mediated vesicles
OT  - macropinosomes
OT  - microglia
OT  - neurovascular unit
OT  - receptor-mediated transcytosis
OT  - transcytosis
OT  - transmission electron microscopy
COIS- The authors declare no conflict of interest.
EDAT- 2023/01/22 06:00
MHDA- 2023/01/25 06:00
PMCR- 2023/01/13
CRDT- 2023/01/21 01:28
PHST- 2022/12/28 00:00 [received]
PHST- 2023/01/09 00:00 [revised]
PHST- 2023/01/12 00:00 [accepted]
PHST- 2023/01/21 01:28 [entrez]
PHST- 2023/01/22 06:00 [pubmed]
PHST- 2023/01/25 06:00 [medline]
PHST- 2023/01/13 00:00 [pmc-release]
AID - ijms24021640 [pii]
AID - ijms-24-01640 [pii]
AID - 10.3390/ijms24021640 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Jan 13;24(2):1640. doi: 10.3390/ijms24021640.