Central nervous system (CNS) pathology is an increasingly recognized consequence of HIV infection. Dementia is a complication of that pathology. Dementia increases the burden of the illness to the patient, caregiver, health care system and society. We know from experience with another dementing disorder, Alzheimer's disease, that strategies which might delay the onset of dementia can have a profoundly beneficial effect. It has been projected by some that even a short delay in onset can produce significant benefit on the national level. At the present time there is a paucity of CNS models for the study of the effects of HIV infection. One of the central objectives of this grant is to characterize the SCID mouse model of HIV CNS infection. By use of contemporary histological techniques, the present study will address basic questions of HIV CNS infection in the SCID mouse. Answers to these questions may have a direct bearing on improving treatment strategies. By understanding how HIV enters the CNS and what it infects in the CNS, existing antiviral therapies may be adapted in a more efficacious way. By use of the SCID mouse model the following questions pertaining to HIV infection of the CNS will be investigated. 1) What is the time course and subsequent CNS pathology produced in this model? 2) Does virus enter the CNS during viremic states or by migrating cells? 3) Do infected human macrophages or T cells induce gliosis in the SCID mouse brain? These aims will require a detailed analysis of the HIV infected reconstituted SCID mouse brain and will include an evaluation of altered synaptic connections, neuromorphologic analysis and an evaluation of stress protein production. Sensitive methods for viral detection and localization will also be used. By these varying histologic approaches it will be possible to investigate the pathophysiologic changes which accompany HIV infection in the SCID mouse. Future directions will examine the efficacy of this model for antiviral drug treatment of the CNS. For example, when should antiviral treatment be initiated to minimize CNS involvement?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29NS031857-01A1
Application #
3478709
Study Section
AIDS and Related Research Study Section 7 (ARRG)
Project Start
1993-08-01
Project End
1998-07-31
Budget Start
1993-08-01
Budget End
1994-07-31
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Texas Tech University
Department
Type
Schools of Medicine
DUNS #
609980727
City
Lubbock
State
TX
Country
United States
Zip Code
79430
Mazzucchelli, Renata; Amadio, Marialaura; Curreli, Sabrina et al. (2004) Establishment of an ex vivo model of monocytes-derived macrophages differentiated from peripheral blood mononuclear cells (PBMCs) from HIV-1 transgenic rats. Mol Immunol 41:979-84
Edelstein, L R; Denaro, F J (2004) The neurobiology of consciousness and Sir Francis Crick. Cell Mol Biol (Noisy-le-grand) 50:671-3
Edelstein, L R; Denaro, F J (2004) The claustrum: a historical review of its anatomy, physiology, cytochemistry and functional significance. Cell Mol Biol (Noisy-le-grand) 50:675-702
Bangura, N; Greenwood, T; James, J et al. (2003) A stereotaxic atlas of the monkey frontal lobes. Cell Mol Biol (Noisy-le-grand) 49:1253-60
Peralta, M; Denaro, F J (2003) The horseradish peroxidase technique for cell lineage studies. Cell Mol Biol (Noisy-le-grand) 49:1371-5
Reid, W; Sadowska, M; Denaro, F et al. (2001) An HIV-1 transgenic rat that develops HIV-related pathology and immunologic dysfunction. Proc Natl Acad Sci U S A 98:9271-6
Denaro, F J; Lopez-Ribot, J L; Chaffin, W L (1995) Adhesion of Candida albicans to brain tissue of Macaca mulata in an ex vivo assay. Infect Immun 63:3438-41