Chemistry or other Changes from Normal
In its most literal form, neurotoxicity could be defined as any departure from normal in the CNS. However, all departures from normal or changes in CNS are not negative. In fact, many compounds deliberately cause changes to the CNS as therapy. Judgment is required as to what changes constitute a negative impact and should be evaluated in the scope of a safety study. Most often, compounds that rely on a specific mechanism of action are evaluated with respect to their impact on the brain relative to that mechanism to make sure intended effects are not also accompanied by unintended ones. There are an incredible number of endpoints that could be evaluated to include a departure from normal. H&E is an example of one of the many tools used to evaluate general changes in the brain. Another common approach is to evaluate endpoints specific to the known mechanism of a compound to specifically quantify their impact on the brain. Examples of endpoints that are evaluated to reveal chemistry changes is the assessment of changes in neurotransmitter systems, as shown in the images below.
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