UC Irvine

The presence within the brain of metal compounds at toxic levels, has adverse consequences for cerebral function. The type of damage that can be incurred often includes the presence of excessive amounts of inflammation. This event does not enhance cerebral defense systems and is thus not an effective or relevant response. On the contrary, such prolonged neuroinflammation can be disruptive to normal brain metabolism. This review outlines several means by which metals can bring about such extended and inappropriate immune activation within the CNS. Various mechanisms that may enable these changes will be discussed, including the formation of haptens, the production of reactive oxygen and nitrogen species, the sequestering of reducing capacity, and the formation of inflammation-provoking colloids. Emphasis is given to the critical nature of the exact form of the metal exerting harmful effects. This can affect both access to, and subsequent disposition within the brain. The interaction of exposure to toxic metals with normal aging events is also considered.