Inflammatory Mechanisms and Cascades Contributing to Neurocognitive Impairment in HIV/AIDS, 2019, Fernandes and Pulliam

[Andy]

Abstract
Neurocognitive impairment caused by chronic human immunodeficiency virus (HIV) infection is a growing concern. In this chapter we discuss the inflammatory mechanisms underlying the pathology of asymptomatic and mild neurocognitive impairment in the context of antiretroviral therapy. We discuss the role of HIV, viral proteins, and virally infected cells on the development of neuroinflammation and the effect of viral proteins on the cells of the central nervous system.

We examine how these collective factors result in an inflammatory context that triggers the development of neurocognitive impairment in HIV. We assess the contribution of antiretrovirals and drugs of abuse, including methamphetamine, cannabis, and opioids, to the neurotoxic and neuroinflammatory milieu that leads to the development of neurocognitive impairment in HIV-infected individuals. We also examined circulating biomarkers, NF-L, sCD163, and sCD14, pertinent to identifying changes in the CNS that could indicate real-time changes in patient physiology. Lastly, we discuss future studies, such as exosomes and the microbiome, which could play a role in the HIV-induced neuroinflammation that eventually manifests as cognitive impairment.

Paywall, https://link.springer.com/chapter/10.1007/7854_2019_100
Sci hub, https://sci-hub.se/10.1007/7854_2019_100

 

[ScottTriGuy]

Things that caught my eye when skimming...

"...studies using animal models of neuroinflammation-induced cognitive damage support the neuroprotective effects of cannabinoids..."

"...suggesting that cannabis use may have a greater effect in suppressing HIV during acute infection..."


"Just as cells take up exosomes, they also release them, and in 2015 neuron-derived exosomes (NDE) were isolated and characterized from the plasma (Goetzl et al. 2015). By using the cell surface marker, L1CAM, for neurons, NDE can be isolated from total plasma exosomes, followed by NDE content analysis. Routine methods such as Western blot, ELISA, PCR, and RNA sequencing can then be utilized to determine the state of the neuron in“real time.” NDE have been characterized and sampled in the periphery for a number of brain pathologies including Alzheimer’s disease (Goetzl et al. 2016, 2018a; Winston et al. 2016), traumatic brain injury (Goetzl et al. 2019), and HIV-associated neurocognitive impairment"


"Monocytes activated with LPS and IFNα in vitro to mimic activated monocytes in HIV infection release exosomes that can be readily transferred to endothelial cells (Dalvi et al. 2017). The exosomes contain abundant miRNAs that can regulate genes at the posttranscriptional level. The functional expression of miR-155 and miR-222 coincided with an increase in CCL2, VCAM, and ICAM, adhesion molecules that modulate vascular function. Manipulation of monocyte miRNAs to overexpress or silence a particular miRNA associated with inflammation might decrease HIV comorbidities such as metabolic and cardiovascular diseases before the M/Mφ cross the endothelium."