Treatment with buprenorphine prior to EcoHIV infection of mice prevents the development of neurocognitive impairment

Abstract

Approximately 15–40% of people living with HIV develop HIV‐associated neurocognitive disorders, HAND, despite successful antiretroviral therapy. There are no therapies to treat these disorders. HIV enters the CNS early after infection, in part by transmigration of infected monocytes. Currently, there is a major opioid epidemic in the United States. Opioid use disorder in the context of HIV infection is important because studies show that opioids exacerbate HIV‐mediated neuroinflammation that may contribute to more severe cognitive deficits. Buprenorphine is an opioid derivate commonly prescribed for opiate agonist treatment. We used the EcoHIV mouse model to study the effects of buprenorphine on cognitive impairment and to correlate these with monocyte migration into the CNS. We show that buprenorphine treatment prior to mouse EcoHIV infection prevents the development of cognitive impairment, in part, by decreased accumulation of monocytes in the brain. We propose that buprenorphine has a novel therapeutic benefit of limiting the development of neurocognitive impairment in HIV‐infected opioid abusers as well as in nonabusers, in addition to decreasing the use of harmful opioids. Buprenorphine may also be used in combination with HIV prevention strategies such as pre‐exposure prophylaxis because of its safety profile.

CCL2 is required for initiation but not persistence of HIV infection mediated neurocognitive disease in mice

“…To assess directly the CCL2 contribution to monocyte migration to the brain, we isolated mononuclear cells from brains of both mouse strains 25 days after EcoHIV infection and performed flow cytometry to detect inflammatory monocytes defined as CD11b + Ly6G neg CD45 high Ly6C + as described 15 , 43 (Fig. S2 in supplementary information on line).…”

CCL2 is required for initiation but not persistence of HIV infection mediated neurocognitive disease in mice

“…Indeed here we show that during systemic infection of CCL2 KO mice in ammatory monocytes are reduced in the brain and EcoHIV DNA was undetectable there. The necessity of monocyte migration to the brain during EcoHIV infection and NCI was recently reported through treatment of mice prior to infection with buprenorphine, an opiate agonist 45 . Brain in ammation and induction of CCL2 are prominent after IC EcoHIV infection of wildtype mice 6,8 .…”

“…To con rm that CCL2 is essential for monocyte migration to the brain, we isolated mononuclear cells from brains of both mouse strains 25 days after EcoHIV infection and performed ow cytometry to detect in ammatory monocytes de ned as CD11b + Ly6G neg CD45 high Ly6C + as described 28,45 . This critical cell type was signi cantly reduced in brains of CCL2 KO mice indicating a requirement for CCL2 for entry into the brain (Fig.…”

Sex specific effects of buprenorphine on behavior, astrocytic opioid receptor expression and neuroinflammation after pediatric traumatic brain injury in mice

“…Studies indicate disparities in the effects of BPN on inflammation, with some studies showing BPN has anti-inflammatory effects and improves cognition ( Hemshekhar et al, 2017 ; Jaureguiberry-Bravo et al, 2021 ), some showing BPN induces oxidative stress and inflammation, and impairs cognition ( Samini et al, 2021 ). In this study, BPN treatment decreased the mRNA expression of iNOS in both males and females at 3-d post-injury, and decreased mRNA expression of IL-1β at 1-d post-injury in females.…”