PMID- 20590523 OWN - NLM STAT- MEDLINE DCOM- 20101112 LR - 20191111 IS - 1875-5739 (Electronic) IS - 1567-2026 (Linking) VI - 7 IP - 3 DP - 2010 Aug TI - Spinal microvascular expression of PV-1 is associated with inflammation, perivascular astrocyte loss, and diminished EC glucose transport potential in acute SCI. PG - 238-50 AB - The endothelial-specific expression of plasmalemmal vesicle associated protein-1 (PV-1) is typical of fenestrated endothelium observed in pulmonary capillaries and some endocrine organs. In the central nervous system (CNS) it is expressed during development but disappears concomitant with maturation of the blood-CNS barrier [1]. Consistent with observations made in models of stroke, Alzheimer's disease, and tumorigenesis, we show PV-1 expression in the spinal cord specifically upregulated by pathologically-activated endothelial cells (ECs) in response to traumatic spinal cord injury (SCI). Adult female C57Bl/6 mice received a moderate T9/10 contusive SCI. PV-1 assessed by qRT-PCR and immunohistochemistry 3 hours to 14 days post-injury showed expression as early as 1 day post-SCI, with levels decreasing by 14 days. This expression was associated with microvessels in the injury epicenter and penumbral zone, with the time course and distribution correlated with progressing peripheral inflammatory cell infiltration. PV-1-immunoreactive ECs were angiogenic as demonstrated by intravascular binding of Griffonia simplicifolia isolectin B4 (IB4). ECs expressing high levels of PV-1 were anatomically and physiologically abnormal with altered/absent immunostaining for occludin and zonula occludens-1 (ZO-1), and decreased expression of glial fibrillary acidic protein (GFAP) and aquaporin-4 (AQP4). Glucose transporter type I (Glut-1) expression decreased in affected, PV-1 positive microvessels with little colocalization of PV-1 and Glut-1 apparent by 7 days post-SCI. These data suggest that upregulation of microvascular expression of PV-1 post-SCI may promote major components of secondary injury including extravasation of cellular and acellular mediators of inflammation and may accelerate loss of neuropil and decline in the functional and anatomical integrity of the neurovascular unit (NVU). FAU - Mozer, Anthony B AU - Mozer AB AD - Kentucky Spinal Cord Injury Research Center, University of Louisville School of Medicine, 511 South Floyd Street, Louisville, KY 40292, USA. FAU - Whittemore, Scott R AU - Whittemore SR FAU - Benton, Richard L AU - Benton RL LA - eng GR - NS045734/NS/NINDS NIH HHS/United States GR - RR15576/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United Arab Emirates TA - Curr Neurovasc Res JT - Current neurovascular research JID - 101208439 RN - 0 (Aquaporin 4) RN - 0 (Carrier Proteins) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Membrane Proteins) RN - 0 (Occludin) RN - 0 (Ocln protein, mouse) RN - 0 (Plvap protein, mouse) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Aquaporin 4/metabolism MH - Astrocytes/*metabolism/pathology MH - Biological Transport MH - Carrier Proteins/*metabolism MH - Endothelial Cells/*metabolism MH - Female MH - Glial Fibrillary Acidic Protein/metabolism MH - Glucose/*metabolism MH - Immunohistochemistry MH - Inflammation/*metabolism/pathology MH - Membrane Proteins/*metabolism MH - Mice MH - Occludin MH - Reverse Transcriptase Polymerase Chain Reaction MH - Spinal Cord Injuries/*metabolism/pathology MH - Thoracic Vertebrae EDAT- 2010/07/02 06:00 MHDA- 2010/11/13 06:00 CRDT- 2010/07/02 06:00 PHST- 2010/05/03 00:00 [received] PHST- 2010/06/18 00:00 [accepted] PHST- 2010/07/02 06:00 [entrez] PHST- 2010/07/02 06:00 [pubmed] PHST- 2010/11/13 06:00 [medline] AID - BSP/CNR/E-Pub/00024 [pii] AID - 10.2174/156720210792231840 [doi] PST - ppublish SO - Curr Neurovasc Res. 2010 Aug;7(3):238-50. doi: 10.2174/156720210792231840.