Excerpt
The adverse impact of environmental chemicals on the human brain has been recognized as an important endpoint in toxicology. In one of the most influential toxicology textbooks, the authors stated in their introduction that … “the target organ of toxicity most frequently involved in systemic toxicity is the CNS” [
1]. Accordingly, the 2nd edition of “Experimental and clinical neurotoxicology”, edited by Peter Spencer and Herbert H. Schaumburg [
2], listed more than 450 compounds that are suspected or proven neurotoxins/toxicants in humans. Naturally occurring neurotoxins, such as domoic acid (DA) or tetrodotoxin (TTX), are among the most potent poisons that can be found in nature, whereas organic solvents are among the man-made neurotoxicants shown to be associated with severe damage in the central and peripheral nervous system [
3]. Already in the early 1980s, Acta Neuropathologica published human biopsy pictures showing demyelination of giant axons taken from the terminal portion of the musculocutaneous nerve of the leg of a patient chronically exposed to
n-hexane and methylethylketone [
4]. Later, details about specific neuropathological changes after chronic solvent abuse via inhalation could be shown in 88 autopsy cases [
5]. In addition to macroscopic findings, such as enlarged ventricles, white matter abnormalities, and cerebral atrophy, the study showed that chronic solvent leukoencephalopathy can be identified by birefringent PAS-staining macrophages and reactive microglia in the white matter. However, the study was not able to disentangle the neuropathological effects of the different solvents that the cases abused simultaneously. Nevertheless, such a neuropathological differential diagnosis was possible in the field of aluminum (Al) neurotoxicity. The neurotoxicity of Al is well known and described in detail for various endpoints and species [
6]. Al exposure has also been linked to the pathogenesis of Alzheimer’s Disease (AD) [
7]. Aluminum neurotoxicity is also thought to play a role in dialysis-associated encephalopathy (DAE) where Al-containing drugs are used to control hyperphosphatemia, and dialysis dementia has been frequently observed as clinical outcome. Despite the proven neurotoxicity of Al, another well-conducted neuropathology study by Reusche et al. [
8] could show that the changes in human brain tissue in DAE patients differed markedly from AD patients. DAE patients did not show AD-type neurofibrillary tangles (NFT) above the normal or expected age-related changes, even though the Al concentrations in the brain samples were markedly increased. These examples illustrate the valuable contributions of neuropathology to the area of toxicology, in particular neurotoxicology. When searching the electronic archive of Acta Neuropathologica, one can find approximately 120 publications related to neurotoxicology but only a few, like the examples given before, included histopathological analyses in human brain tissue. Moreover, these studies were mostly performed under conditions of high exposures or even intoxication. During the last decades, only a few neurotoxicity studies or reviews have been published that have a strong focus on human neuropathology (e.g., [
9]). This deficit has been identified by the former Editor-in-Chief, Werner Paulus, who developed and initiated the idea of a cluster of reviews addressing current hot topics in neurotoxicology. This was a challenging endeavour as there are some differences between these obviously-related disciplines. …
