Core--cell, tissue and animal facility

University Of Rochester, Rochester NY

Investigators

Linked publications & trials

Abstract

DESCRIPTION: (Provided by applicant): The purpose of this core is to assist in the design of adjunctive therapeutic strategies for treatment and/or prevention of neurologic disease following human immunodeficiency virus type-one (HIV-1) infection. In this regard, purified human monocyte-derived macrophages (MDM) and MDM conditioned media (MCM) will be supplied, following HIV-1 infection and/or immune activation, to all investigators on request, within the Rochester Cooperative NeuroAIDS Drug Discovery Group (RCNDDG). In addition, promising anti-inflammatory and/or neuroprotective drugs, developed in laboratory assays or proposed, will be tested for therapeutic efficacy in a severe combined immune deficiency (SCID) mouse model of HIV-1 encephalitis (HIVE). Brain tissue and/or sera will be made available for measuring drug levels and pathology in the HIVE mice. Such works will support translational (bench to bedside) research efforts and directly effect the performance of subsequent clinical trials. The works, in toto, are based on the concept that HIV-1 associated dementia (HAD) is, in part, a reversible metabolic encephalopathy caused by defective immunity of virus-infected mononuclear phagocytes [(MP), microglia, perivascular and parenchymal macrophages]. These MPs serve both as reservoirs for productive HIV-1 infection and principal sources of neurotoxic activities within the central nervous system (CNS). The development of ways to inhibit toxic inflammatory activities in brain may serve to both ameliorate and prevent complications of persistent viral replication in brain serving as critical adjunctive therapies to ongoing potent anti-retroviral regimens, the principal goals of the RCNDDG.