As researchers across the globe have focused their attention on understanding SARS-CoV-2, the picture that is emerging is that of a virus that has serious effects on the vasculature in multiple organ systems including the cerebral vasculature. Observed effects on the central nervous system include neurological symptoms (headache, nausea, dizziness), fatal microclot formation and in rare cases encephalitis. However, our understanding of how the virus causes these mild to severe neurological symptoms and how the cerebral vasculature is impacted remains unclear. Thus, the results presented in this report explored whether deleterious outcomes from the SARS-CoV-2 viral spike protein on primary human brain microvascular endothelial cells (hBMVECs) could be observed. The spike protein, which plays a key role in receptor recognition, is formed by the S1 subunit containing a receptor binding domain (RBD) and the S2 subunit. First, using postmortem brain tissue, we show that the angiotensin converting enzyme 2 or ACE2 (a known binding target for the SARS-CoV-2 spike protein), is ubiquitously expressed throughout various vessel calibers in the frontal cortex. Moreover, ACE2 expression was upregulated in cases of hypertension and dementia. ACE2 was also detectable in primary hBMVECs maintained under cell culture conditions. Analysis of cell viability revealed that neither the S1, S2 or a truncated form of the S1 containing only the RBD had minimal effects on hBMVEC viability within a 48 h exposure window. Introduction of spike proteins to in vitro models of the blood-brain barrier (BBB) showed significant changes to barrier properties. Key to our findings is the demonstration that S1 promotes loss of barrier integrity in an advanced 3D microfluidic model of the human BBB, a platform that more closely resembles the physiological conditions at this CNS interface. Evidence provided suggests that the SARS-CoV-2 spike proteins trigger a pro-inflammatory response on brain endothelial cells that may contribute to an altered state of BBB function. Together, these results are the first to show the direct impact that the SARS-CoV-2 spike protein could have on brain endothelial cells; thereby offering a plausible explanation for the neurological consequences seen in COVID-19 patients.

Intimate partner violence (IPV) is prevalent among young gay and bisexual men (YGBM) and is associated with physical and mental health problems, as well as deleterious psychosocial conditions. Most previous studies of IPV among YGBM have been quantitative in nature and have not examined the numerous subtypes of IPV, the chronicity of IPV experiences, and how is IPV manifested in the context of these same-sex relationships. Thus, a qualitative approach may be useful in exploring these multidimensional and understudied experiences. The present qualitative study sought to (a) explore dimensions of IPV victimization, perpetration, and bidirectional IPV among a sample of ( n = 26) YGBM living in New York City and (b) explore the chronicity of IPV experiences among these YGBM. Participants were recruited from an ongoing cohort study of YGBM. Participants completed semistructured interviews that included questions about IPV victimization, perpetration, and bidirectional IPV. A modified version of the consensual qualitative research method was used to analyze the data. The YGBM in this study reported numerous forms of physical, psychological, sexual, and financial IPV victimization and perpetration. Bidirectional experiences of IPV were common. The various subtypes of IPV victimization and perpetration are explored in detail in this manuscript. In addition, many participants reported multiple experiences of abuse within the same relationship, and some participants experienced a pattern of abusive relationships over time. This study corroborates findings from quantitative studies, which indicate that IPV is a prevalent and significant health problem among YGBM, and one that warrants additional attention from researchers, practitioners, and policy-makers. Furthermore, this study adds rich qualitative data to the existing literature—data that can be used to help develop and refine future measures of IPV that are tailored for use with YGBM.

Tissue engineering of the blood-brain barrier (BBB) in vitro has been rapidly expanding to address the challenges of mimicking the native structure and function of the BBB. Most of these models utilize 2D conventional microfluidic techniques. However, 3D microvascular models offer the potential to more closely recapitulate the cytoarchitecture and multicellular arrangement of in vivo microvasculature, and also can recreate branching and network topologies of the vascular bed. In this perspective, we discuss current 3D brain microvessel modeling techniques including templating, printing, and self-assembling capillary networks. Furthermore, we address the use of biological matrices and fluid dynamics. Finally, key challenges are identified along with future directions that will improve development of next generation of brain microvasculature models.

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Treatment of HIV-infected patients with antiretroviral therapy (ART) has effectively suppressed viral replication; however, the central nervous system is still a major target and reservoir of the virus leading to the possible development of HIV-associated neurocognitive disorders (HAND). Furthermore, a hallmark feature of HAND is the disruption of the blood–brain barrier that leads to loss of tight junction protein (TJP) complexes. Extracellular vesicles (EVs), released by every cell type in the body, occur in greater quantities in response to cellular activation or injury. We have found that inflammatory insults activate brain endothelial cells (EC) and induce the release of EVs containing TJPs such as Occludin. We thus hypothesized that HIV infection and unresolved neuroinflammation will result in the release of brain-EC derived EVs. Herein, our results show elevated levels of brain-EC EVs in a humanized mouse model of HIV infection. Furthermore, while ART reduced brain-EC EVs, it was unable to completely resolve increased vesicles detectable in the blood. In addition to inflammatory insults, HIV-1 viral proteins (Tat and gp120) increased the release of Occludin + vesicles from human brain microvasculature ECs. This increase in vesicle release could be prevented by knock-down of the small GTPase ARF6. ARF6 has been shown to regulate EV biogenesis in other cell types, and we provide further evidence for the involvement of ARF6 in brain EC derived EVs. Overall, this study offers insight into the process of brain vascular remodeling (via EVs) in the setting of neuroinflammation and thus provides possibilities for biomarker monitoring and targeting of ARF6. Graphical abstract