# Targeting Inflammasomes in Substance Abuse and HIV

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2023 · $430,150

## Abstract

ABSTRACT
This application aims to investigate the impact of HIV brain infection and prescription opioids on
ischemic stroke, a major co-morbidity in the infected population and opioid abusers. We recently
identified that brain infection by HIV increases susceptibility to ischemic stroke, leading to
reactivation of HIV. Importantly, this effect was associated with activation of the inflammasome.
While the impact of opioids, such as morphine and oxycodone, on these events is unknown, we
have evidence that chronic exposure to opioids can enhance tissue damage in ischemic stroke
and activate the inflammasome. In line with these observations, the central hypothesis of the
current grant is that HIV and prescription opioids activate inflammasome in the CNS that
can worsen stroke outcome, including post-stroke HIV reactivation in the CNS and egress
into the periphery. In Aim 1 of the proposed work, we will evaluate the mechanisms of
inflammasome activation by HIV infection and prescription opioids. In Aim 2, we will
therapeutically target mitochondria for protection against HIV and opioid-induced inflammasome
activation, leading to improvement of stroke outcome and recovery. In Aim 3, we will study the
impact of opioid-induced inflammasome activation on HIV reactivation in the CNS and egress into
the periphery in ischemic stroke. Several conceptual, mechanistic, and technical aspects of this
application are highly innovative. For example, the focus on the impact of HIV and prescription
opioids on ischemic stroke outcome is an understudied area of research and constitutes a
conceptual innovation of the proposal. Our findings that the inflammasome can be involved in HIV
reactivation from brain reservoirs has never been reported before.
In concert, Aims 1 and 2 will provide critical insight into the role of inflammasome in stroke
development of HIV-infected patients who are opioid abusers. Aim 3 will provide important
information on the reactivation of HIV from the brain and seeding into the periphery as the result
of inflammasome activation in stroke. The proposed research is highly innovative because of its
focus on novel mechanisms underlying vascular comorbidities, such as ischemic stroke, in the
HIV-infected brain in the context of opioid abuse. These studies are also likely to identify new
opportunities for therapeutic intervention.

## Key facts

- **NIH application ID:** 10645136
- **Project number:** 5R01DA050528-04
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Michal Toborek
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $430,150
- **Award type:** 5
- **Project period:** 2020-07-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10645136

## Citation

> US National Institutes of Health, RePORTER application 10645136, Targeting Inflammasomes in Substance Abuse and HIV (5R01DA050528-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10645136. Licensed CC0.

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