The following model of brain degeneration developed in Luxembourg by CRP-Sante seems to fit HD. The prostaglandin E(2) are pro-inflammatory and generally considered bad guys. They are elevated in HD and also produced from dietary omega-6 fats. Western diets are usually too high in omega-6 fats.

The microglial cells are the immune surveillance cells of the brain. They are activated in HD. In my model of HD they are upstream to the events of HD. It is progress that the immune system has been promoted from 'down stream' to 'controversial' in the progression of HD. --Jerry 09-Apl-2001
Neurochem Int 2001 Jun 1;38(7):557-565; Hemmer K, et al.

An in vitro model for the study of microglia-induced neurodegeneration: involvement of nitric oxide and tumor necrosis factor-alpha.

The precise function of activated microglia and their secretory products remains controversial.

In order to assess the role of microglial secretion products, we established an in vitro model of an inflammatory reaction in the brain by co-culturing microglial and neuronal cell lines. Upon stimulation with interferon-gamma and lipopolysaccharides, the microglial cells adopted an activated phenotype and secreted tumor necrosis factor-alpha (TNF-alpha), prostaglandin E(2) and nitric oxide (NO).

Neuronal degeneration was quantified by measuring the concentrations of microtubule associated protein tau and neuron specific enolase, which are also used as diagnostic tool in Alzheimer's disease, in supernatants. In activated contact co-cultures, the levels of these neuronal markers were significantly raised compared to non-activated co-cultures. NO-synthase inhibitors significantly diminished the rise of tau in activated co-cultures, while indomethacin, superoxide dismutase, or a neutralizing TNF-alpha antibody did not.

When a chemical NO-donor or TNF-alpha were added to pure neuronal cultures, cell viability was significantly reduced. TNF-alpha increased neuronal sensitivity towards NO. There were indications that a part of the cells died by apoptosis.

This model demonstrates a neurotoxic role for NO in microglia-induced neurodegeneration and provides a valuable in vitro tool for the study of microglia-neuron interactions during inflammation in the brain.