TMARC Pilot Studies - Completed

Effect of METH Use on Vascular Pathology in the HIV-infected Brain (Soontornniyomkij)

Agency: TMARC
PI: Soontornniyomkij, Virawudh, M.D.

Abstract

Severe cerebrovascular complications of METH use include subarachnoid hemorrhage, ischemic stroke, and intracerebral hemorrhage. In this regard, angiographic abnormalities of the cerebral vasculature have been sporadically reported, while autopsy studies are limited to few case reports. MRI studies revealed white matter signal hyperintensities in METH users, suggesting the presence of small vessel disease. In HIV+ individuals, vascular pathology associated with METH use has not been explored. Chronic METH exposure may lead to repeated episodes of hypertension, resulting in cerebrovascular injury, and to vascular endothelial toxicity. Both METH and HIV individually can induce disruption of blood-brain barrier (BBB) tight junctions.

We aim to study vascular pathology in the setting of HIV and METH comorbidities in the brains of HIV+ men with lifetime diagnosis of METH dependence. We will assemble autopsy tissue blocks from the prefrontal cortex, deep frontal white matter, and basal ganglia of 30 METH+/HIV+ cases, 30 METH-/HIV+ cases, and 10 METH-/HIV- cases. The age, presence of systemic diseases at risk for stroke, use of substances (other than METH), and antiretroviral regimens will be matched between the two HIV+ groups. Cases with opportunistic CNS diseases or HCV seropositivity will be excluded. To identify vasculopathic lesions, we will review all the H&E autopsy brain slides and on the three tissue blocks requested employ immunoperoxidase staining for vascular smooth muscle actin, β-amyloid, BBB tight-junction proteins (ZO-1 and occludin), and microglia/macrophage marker. We hypothesize that METH dependence correlates with the prevalence and severity of selective forms of cerebrovascular pathology. We plan to compare the results of this autopsy study with those of HIV-1 gp120 transgenic mice exposed to METH.

Sponsored by NIH/NIDA P50DA026306

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