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Journal of Neuroimmune Pharmacology

, Volume 9, Issue 4, pp 447–453 | Cite as

Cannabinoid Receptor-2 and HIV-Associated Neurocognitive Disorders

  • Vishnudutt PurohitEmail author
  • Rao S. Rapaka
  • Joni Rutter
PERSPECTIVE

Abstract

Despite the wide spread use of highly active antiretroviral therapy (HAART), mild forms of HIV-associated neuro cognitive disorders (HAND) remain commonplace. HAART treated patients now show low levels of viremia and more subtle yet biologically important signs of brain macrophage and microglial activation. Adjunctive therapeutic strategies are required to eliminate HIV-1 infection and suppress immune activation and its associated neuroinflammation. In this regard, cannabinoid receptor-2(CB2) activation is a promising means to attenuate HAND by inhibiting HIV replication, down regulating inflammation, and suppressing chemokine-like activity of viral neurotoxic proteins (for example, Tat and HIV-1gp120), and thereby prevent neuronal and synaptic loss. Inhibiting even low level HIV replication can attenuate neuronal injury by decreasing the production of neurotoxins. Down regulation of inflammation by CB2 activation is mediated through blunted activation of peri vascular macrophages and microglia; decreased production of tumor necrosis factor-α, chemokines and virotoxins. Down regulated neuroinflammation can decrease blood brain barrier permeability and leukocyte infiltration resulting in reduced neuronal injury. It is suggested that CB2 agonists may further attenuate HAND in HIV-infected patients on HAART. In addition, CB2 activation may also blunt brain injury by attenuating drug addiction.

Keywords

HIV-associated neurocognitive disorders Highly active antiretroviral therapy Cannabinoid receptor type 2 Neuroinflammation Macrophages and microglia Blood brain barrier 

Notes

Conflict of Interest Statement

Authors declare no conflict of interest.

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Copyright information

© Springer Science+Business Media New York (outside the USA) 2014

Authors and Affiliations

  • Vishnudutt Purohit
    • 1
    Email author
  • Rao S. Rapaka
    • 1
  • Joni Rutter
    • 1
  1. 1.Chemistry and Physiological Systems Research Branch Division of Basic Neuroscience & Behavioral ResearchNational Institute on Drug Abuse National Institutes of HealthBethesdaUSA

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