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Blood-brain barrier abnormalities caused by exposure to HIV-1 gp120--protection by gene delivery of antioxidant enzymes.
Neurobiol Dis. 2010 May; 38(2):313-25.ND

Abstract

HIV-1 effects on the blood-brain barrier (BBB) structure and function are still poorly understood in animal models based on direct administration of recombinant HIV proteins. We therefore injected HIV-1 envelope glycoprotein, gp120, into rat caudate-putamens (CPs) and examined vascular integrity and function. Gp120 coimmunostained with endothelial cell marker, CD31. It induced apoptosis of endothelial cells in vitro and in vivo. BBB function was assessed by administering Evans Blue (EB) intravenously before injecting gp120. EB leaked near the site of gp120 administration. Within 1h after intra-CP gp120 injection, structures positive for endothelial markers ICAM-1 and RECA-1 were greatly decreased. Vascular density assessed by laminin immunostaining remained decreased 1 month after gp120 injection. RECA-1-positive cells expressed hydroxynonenal, a marker of lipid peroxidation and rSV40-mediated gene delivery of antioxidant enzymes protected the BBB from gp120-related injury. Extravasated IgG accumulated following intra-CP SV(gp120) injection, an experimental model of continuing gp120 exposure. Thus: acute and chronic exposure to gp120 disrupts the BBB; gp120-mediated BBB abnormalities are related to lesions of brain microvessels; and gp120 is directly toxic to brain endothelial cells.

Authors+Show Affiliations

Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA. jplouboutin@hotmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

20219678

Citation

Louboutin, Jean-Pierre, et al. "Blood-brain Barrier Abnormalities Caused By Exposure to HIV-1 Gp120--protection By Gene Delivery of Antioxidant Enzymes." Neurobiology of Disease, vol. 38, no. 2, 2010, pp. 313-25.
Louboutin JP, Reyes BA, Agrawal L, et al. Blood-brain barrier abnormalities caused by exposure to HIV-1 gp120--protection by gene delivery of antioxidant enzymes. Neurobiol Dis. 2010;38(2):313-25.
Louboutin, J. P., Reyes, B. A., Agrawal, L., Maxwell, C. R., Van Bockstaele, E. J., & Strayer, D. S. (2010). Blood-brain barrier abnormalities caused by exposure to HIV-1 gp120--protection by gene delivery of antioxidant enzymes. Neurobiology of Disease, 38(2), 313-25. https://doi.org/10.1016/j.nbd.2010.02.007
Louboutin JP, et al. Blood-brain Barrier Abnormalities Caused By Exposure to HIV-1 Gp120--protection By Gene Delivery of Antioxidant Enzymes. Neurobiol Dis. 2010;38(2):313-25. PubMed PMID: 20219678.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Blood-brain barrier abnormalities caused by exposure to HIV-1 gp120--protection by gene delivery of antioxidant enzymes. AU - Louboutin,Jean-Pierre, AU - Reyes,Beverly A S, AU - Agrawal,Lokesh, AU - Maxwell,Christina R, AU - Van Bockstaele,Elisabeth J, AU - Strayer,David S, Y1 - 2010/02/26/ PY - 2009/11/04/received PY - 2010/01/13/revised PY - 2010/02/15/accepted PY - 2010/3/12/entrez PY - 2010/3/12/pubmed PY - 2010/7/2/medline SP - 313 EP - 25 JF - Neurobiology of disease JO - Neurobiol Dis VL - 38 IS - 2 N2 - HIV-1 effects on the blood-brain barrier (BBB) structure and function are still poorly understood in animal models based on direct administration of recombinant HIV proteins. We therefore injected HIV-1 envelope glycoprotein, gp120, into rat caudate-putamens (CPs) and examined vascular integrity and function. Gp120 coimmunostained with endothelial cell marker, CD31. It induced apoptosis of endothelial cells in vitro and in vivo. BBB function was assessed by administering Evans Blue (EB) intravenously before injecting gp120. EB leaked near the site of gp120 administration. Within 1h after intra-CP gp120 injection, structures positive for endothelial markers ICAM-1 and RECA-1 were greatly decreased. Vascular density assessed by laminin immunostaining remained decreased 1 month after gp120 injection. RECA-1-positive cells expressed hydroxynonenal, a marker of lipid peroxidation and rSV40-mediated gene delivery of antioxidant enzymes protected the BBB from gp120-related injury. Extravasated IgG accumulated following intra-CP SV(gp120) injection, an experimental model of continuing gp120 exposure. Thus: acute and chronic exposure to gp120 disrupts the BBB; gp120-mediated BBB abnormalities are related to lesions of brain microvessels; and gp120 is directly toxic to brain endothelial cells. SN - 1095-953X UR - https://www.unboundmedicine.com/medline/citation/20219678/Blood_brain_barrier_abnormalities_caused_by_exposure_to_HIV_1_gp120__protection_by_gene_delivery_of_antioxidant_enzymes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0969-9961(10)00054-9 DB - PRIME DP - Unbound Medicine ER -