We should not discount the nutritional approach. It may be a safer way to go, with fewer dire unintended consequences. Tnfa antagonists have caused problems in patients. Maybe there is something we can eat that will prevent microglia overactivation in the first place. Overactivation leads to the microglia dying which is thought to be a self regulatory mechanism to protect other neurons. But we don't want microglia dying because our brains have a limited number of them.

"Microglia are the resident immune cells of the brain and play a role in immune surveillance under normal condition. However, microglia become readily activated in response to infections and neuronal injuries under pathological condition [5].

Activated microglia produce a wide array of factors, including cytokines such as TNF-greek small letter alpha and IL-β, reactive oxygen species, reactive nitrative species such as NO, and eicosanoids.

These factors are believed to contribute to microglia-mediated neurodegeneration [3] G.H. Jeohn, L.Y. Kong, B. Wilson, P. Hudson and J.S. Hong, Synergistic neurotoxic effects of combined treatments with cytokines in murine primary mixed neuron/glia cultures, J. Neuroimmunol. 85 (1998), pp. 1–10.

Recent studies indicated that minocycline, a tetracycline derivative, exhibits a neuroprotective effect by inhibiting microglia activation in several models of neurodegeneration [13] and [14].

Similarly, Liu et al. have shown that naloxone protects dopaminergic neurons against inflammatory damage through inhibition of microglia activation [7].

Wang et al. have demonstrated that silymarin, a polyphenol flavonoid derived from milk thistle, protects dopaminergic neurons against LPS-induced neurotoxicity by inhibiting microglia activation in mesencephalic neuron-glia cultures [17].

Moreover, Liu et al. have reported that dextromethorphan protects dopaminergic neurons against inflammation-mediated degeneration through inhibition of microglia activation [10].
These observations suggest that the agents which inhibit microglia activation will provide neuroprotective effects.

In the present study, we have shown that biochanin A effectively inhibited microglia activation and release of TNF-greek small letter alpha, NO, and superoxide in mesencephalic neuron-glia cultures and microglia-enriched cultures exposed to LPS treatment, indicating that the mechanism of action underlying the neuroprotective role of biochanin A, at least partially, is attributed to the inhibition of microglia activation."



From:

Biochanin A protects dopaminergic neurons against lipopolysaccharide-induced damage through inhibition of microglia activation and proinflammatory factors generation

Han-Qing Chena, b, Zheng-Yu Jina, Corresponding Author Contact Information, E-mail The Corresponding Author and Guan-Hong Li

Neuroscience Letters
Volume 417, Issue 2, 1 May 2007

Abstract

Activation of microglia and consequent release of proinflammatory factors, are believed to contribute to neurodegeneration in Parkinson's disease (PD). Hence, identification of compounds that prevent microglial activation is highly desirable in the search for therapeutic agents for inflammation-mediated neurodegenerative diseases.

In this study, we reported that biochanin A, one of the predominant isoflavones in Trifolium pratense, attenuated lipopolysaccharide (LPS)-induced decrease in dopamine uptake and the number of dopaminergic neurons in a dose-dependent manner in rat mesencephalic neuron-glia cultures.

Moreover, biochanin A also significantly inhibited LPS-induced activation of microglia and production of tumor necrosis factor-greek small letter alpha, nitric oxide and superoxide in mesencephalic neuron-glia cultures and microglia-enriched cultures.

This study suggested for the first time that biochanin A protected dopaminergic neurons against LPS-induced damage through inhibition of microglia activation and proinflammatory factors generation.


http://www.sciencedirect.com/science...9cf8010c9e3214