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However, the brain is a viral reservoir, and pathologies such as cognitive decline and blood\u2013brain barrier (BBB) disruption persist. Methamphetamine abuse is prevalent among HIV\u2010infected individuals. Methamphetamine and HIV toxic proteins can disrupt the BBB, but it is unclear if there exists a common pathway by which HIV proteins and methamphetamine induce BBB damage. Also unknown are the BBB effects imposed by chronic exposure to HIV proteins in the comorbid context of chronic methamphetamine abuse. To evaluate these scenarios, we trained HIV\u20101 transgenic (Tg) and non\u2010Tg rats to self\u2010administer methamphetamine using a 21\u2010day paradigm that produced an equivalency dose range at the low end of the amounts self\u2010titrated by humans. Markers of BBB integrity were measured for the hippocampus, a brain region involved in cognitive function. Outcomes revealed that tight junction proteins, claudin\u20105 and occludin, were reduced in Tg rats independent of methamphetamine, and this co\u2010occurred with increased levels of lipopolysaccharide, albumin (indicating barrier breakdown) and matrix metalloproteinase\u20109 (MMP\u20109; indicating barrier matrix disruption); reductions in GFAP (indicating astrocytic dysfunction); and microglial activation (indicating inflammation). Evaluations of markers for two signaling pathways that regulate MMP\u20109 transcription, NF\u2010\u03baB and ERK\/\u2206FosB revealed an overall genotype effect for NF\u2010\u03baB. Methamphetamine did not alter measurements from Tg rats, but in non\u2010Tg rats, methamphetamine reduced occludin and GFAP, and increased MMP\u20109 and NF\u2010\u03baB. Study outcomes suggest that BBB dysregulation resulting from chronic exposure to HIV\u20101 proteins or methamphetamine both involve NF\u2010\u03baB\/MMP\u20109.<\/jats:p>","DOI":"10.1111\/ejn.14925","type":"journal-article","created":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T14:26:33Z","timestamp":1596032793000},"page":"416-429","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Hippocampal blood\u2013brain barrier of methamphetamine self\u2010administering HIV\u20101 transgenic rats"],"prefix":"10.1111","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1004-3568","authenticated-orcid":false,"given":"Michael","family":"Ohene\u2010Nyako","sequence":"first","affiliation":[{"name":"Department of Pharmacology Rush University Chicago IL USA"},{"name":"Department of Physician Assistant Studies Rush University Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8494-3721","authenticated-orcid":false,"given":"Amanda L.","family":"Persons","sequence":"additional","affiliation":[{"name":"Department of Physician Assistant Studies Rush University Chicago IL USA"},{"name":"Department of Psychiatry and Behavioral Sciences Rush University Chicago IL USA"},{"name":"Center for Compulsive Behavior and Addiction Rush University Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T. 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