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Studies on the efficacy of neuronal receptor antagonists and anti-inflammatory agents on the prevention of neuronal injury in hiv encephalitis

Objective



Research objectives and content
Many adults and especially children with AIDS suffer from AIDS Dementia due to the HIV replication in brain tissue. Interestingly, neurons, the primary cell responsible for memory and motor functions, are not infected by the virus. In contrast, immune cells called macrophages and microglia are the principal target cells for virus. It is known that brain macrophages, when immune activated produce factors that damage neurons. In order to understand the way neurotoxins are manufactured during virus infection, we will develop an experimental system that consists of cocultures between HIV-1-infected macrophages and neurons that allow quantitative studies on the outgrowth of neurites. Since the characteristics of outgrowth of neurites affect neuronal development and survival, this model can be used to evaluate the reversible effect of therapeutic treatment of neuronal injury mediated by HIV-infected macrophages. Therefore, we wish to evaluate the efficacy of two groups of compounds that either protects neurons from injury and death or prevents the detrimental effects of neurotoxin production by HIV-infected brain macrophages in order to develop therapeutic strategies for this HIV-associated neurological disease.
Training content (objective, benefit and expected impact)
The main objective of this proposal is the development of unique in-vitro models. That will require great knowledge in cell culture techniques, monocyte isolation, PCR and ELISA The drug trials are a challenge because the drug quantities are not yet defined and have to be studied and tested. The goal is to find drugs that can prevent neuronal injury and that are suitable for in-vivo testing and maybe, in the future, some new drug can be produced for
Links with industry / industrial relevance (22)
This project can be inserted into the 'Viral Diseases' Research-Industry Task Force. It is a long-term goal of us that, in the . future, industry involvement in this project can take place and commercialisation of a new drug against HIV neuropathogenic effects can be a reality.

Funding Scheme

RGI - Research grants (individual fellowships)

Coordinator

Rijksuniversiteit Utrecht
Address
100,Heidelberglaan 100
3584 CX Utrecht
Netherlands