The National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Mental Health (NIMH) encourage applications for research on the role of neuroinflammation in the initiation and expansion of cellular injury and death in HIV-1 infection of the central nervous system (CNS).*
Neurological dysfunction is a devastating complication of HIV-1 infection. Recent evidence indicates that microglial and astrocytic activation results in the release of excitotoxins, arachidonic acid metabolites, reactive oxygen species, cytokines, and chemokines that lead to neurodegeneration and cognitive impairment in HIV-1 infected individuals. The pathophysiological mechanisms underlying the changes in neurological function are as yet unresolved but may include neuroinflammatory responses to HIV-1 infection.
Examples of potential areas of research interest include studies to: investigate the role of microglia and astrocytes in the etiology of AIDS dementia; advance studies on cell-cell interactions in the neuroinflammatory cascade; investigate the roles of excitotoxicity, the production of nitric oxide, and the production of reactive oxygen species as mechanisms of neuropathogenesis in HIV-1 infection of the CNS; define phenotypic markers which characterize activated microglia and astrocytes in the context of HIV-1 infection of the nervous system; delineate the contribution of microglia and astrocytes to the development of inflammation of the HIV-1 infected CNS via antigen presentation or production of specific cytokines and chemokines; investigate contributions of perivascular microglia and astrocytes to the entry of blood macrophages into the CNS across the blood-brain barrier; investigate the role of HIV-1 proteins in the activation of microglia and astrocytes, or their role in mediating damage to neurons; develop animal models of HIV-1 induced neuroinflammation; develop assays that use human neurons as targets of HIV-1 induced neuroinflammation; and delineate apoptotic pathways involved in the death of CNS cells in the context of HIV-1 infection.
For more information, potential applicants should contact Dr. Michael Nunn, Program Director, Neural Environment Cluster, NINDS, Neuroscience Center, 6001 Executive Boulevard, Room 2118, Bethesda, MD 20892; telephone: 301-496-1431; fax: 301-480-2424; e-mail: firstname.lastname@example.org.
*For a more detailed description of this program announcement, please visit the NIH web site at: http://grants.nih.gov/grants/guide/pa-files/PAS-03-084.html.