Mechanisms of Toxic Injury in the Peripheral Nervous System: Neuropathologic Considerations

Abstract

The anatomical distribution and organization of the peripheral nervous system as well as its frequent ability to

Methods to identify and characterize developmental neurotoxicity for human health risk assessment. II: neuropathology.

“…As noted above, peripheral nerve from younger, nonperfused animals can be evaluated similarly. The sciatic nerve in these animals is accessible and can be fixed adequately by immersion (81). The developmental state of this nerve at PND11 and beyond is adequate for qualitative and quantitative histopathology (78).…”

“…The denser epoxy resin plastics allow embedding of nerve that has been postfixed in osmium tetroxide, a process that enhances histologic contrast (80). These tissue preparations can be sectioned at approximately 1 µm thickness and with appropriate stains provide the high level of optical resolution needed for critical histologic evaluation, including morphometric assessment of myelinated fibers (81). Therefore, the use of epoxy resin for the embedding media is desirable (80).…”

Pyridoxine (vitamin B6) neurotoxicity: enhancement by protein‐deficient diet

“…Paraffin-embedded blocks were cut at 5 µm and stained with hematoxylin and eosin or cresyl violet for Nissl bodies. Histological lesions of the large trigeminal neurons were loss of Nissl bodies (central chromatolysis), peripheral displacement of nuclei and irregular or indented nuclear membranes, as described by others (Antopol and Tarlov, 1942;Krinke et al, 1985;Windebank et al, 1985;Xu et al, 1989;Jortner, 2000). When these changes were present in all large neurons, the lesions were designated as severe.…”

“…Pyridoxine is especially toxic to the peripheral nervous system (Antopol and Tarlov, 1942;Krinke et al, 1985;Windebank et al, 1985;Xu et al, 1989;Jortner, 2000). This aspect of the vitamin has special interest because it is not known if its toxicity is related to one or more of its numerous physiological functions or to a still unknown metabolite of the original molecule or of the other vitamers to which it may be converted in vivo.…”

Preparation and Analysis of the Peripheral Nervous System

“…If the neurons are severely injured or necrotic, then peripheral nerve regeneration is not possible (Figure 8). The mechanism of pyridoxine neuronotoxicity is not fully understood, but it is thought that high circulating levels of pyridoxine might have a direct toxic effect on neurons of the peripheral sensory ganglia (Jortner 2000), which may relate to the presence of a lower (''leaky'') blood nerve barrier in such regions (Olsson 1984). The more complete blood-brain barrier in the central nervous system, along with a saturable pyridoxine transport system, protects neurons in those regions from high blood levels of pyridoxine (Schaumburg 2000).…”