Synergistic Impairment of the Neurovascular Unit by HIV-1 Infection and Methamphetamine Use: Implications for HIV-1-Associated Neurocognitive Disorders

Abstract

The neurovascular units (NVU) are the minimal functional units of the blood­–brain barrier (BBB), composed of endothelial cells, pericytes, astrocytes, microglia, neurons, and the basement membrane. The BBB serves as an important interface for immune communication between the brain and peripheral circulation. Disruption of the NVU by the human immunodeficiency virus-1 (HIV-1) induces dysfunction of the BBB and triggers inflammatory responses, which can lead to the development of neurocognitive impairments collectively known as HIV-1-associated neurocognitive disorders (HAND). Methamphetamine (METH) use disorder is a frequent comorbidity among individuals infected with HIV-1. METH use may be associated not only with rapid HIV-1 disease progression but also with accelerated onset and increased severity of HAND. However, the molecular mechanisms of METH-induced neuronal injury and cognitive impairment in the context of HIV-1 infection are poorly understood. In this review, we summarize recent progress in the signaling pathways mediating synergistic impairment of the BBB and neuronal injury induced by METH and HIV-1, potentially accelerating the onset or severity of HAND in HIV-1-positive METH abusers. We also discuss potential therapies to limit neuroinflammation and NVU damage in HIV-1-infected METH abusers.

A Prospective Viewpoint on Neurological Diseases and Their Biomarkers

“…Local inflammation is frequently triggered by BBB endothelial cells that are equipped with the molecular machinery to detect bacterial and viral antigens. The antigenic recognition of a broad number of conserved molecular determinants known as pathogen-associated molecular patterns (PAMPs; Hanke and Kielian, 2011) by pattern recognition receptors (PRRs) is the first line of defense against microbial invasion [ 111 , 112 ]. Peripheral variables such as the gut microbiome can influence the condition of NDDs [ 113 ].…”

Methamphetamine Enhancement of HIV-1 gp120-Mediated NLRP3 Inflammasome Activation and Resultant Proinflammatory Responses in Rat Microglial Cultures

“…Immune activation and neuroinflammation, which are linked to viral proteins and drugs of abuse, continue to play pivotal roles in HAND pathogenesis. Meth abuse exacerbates the HANDs seen clinically, and the mechanism(s) underlying this remains unclear [23,53,54]. To understand how Meth exacerbates HANDs, we studied the augmentation effects of Meth on HIV-1 gp120-induced microglial NLRP3 inflammasome activation and the resultant proinflammatory cytokine production.…”

Methamphetamine enhancement of HIV-1 gp120-mediated NLRP3 inflammasome activation and resultant proinflammatory responses in rat microglial cultures

“…Immune activation and neuroinflammation, which are linked to viral proteins and drugs of abuse, continue to play pivotal roles in HAND pathogenesis. Meth abuse exacerbates the HAND seen clinically and the mechanism(s) underlying such an exacerbation remain unclear [ 23 , 55 , 56 ]. To understand how Meth exacerbates HAND we studied the augment effects of Meth on HIV-1 gp120-induced microglial NLRP3 inflammasome activation and resultant proinflammatory cytokine production.…”