“Current Pathology Techniques” Symposium Review: Advances and Issues in Neuropathology

Abstract

Our understanding of the mechanisms that incite neurological diseases has progressed rapidly in recent years, mainly owing to the advent of new research instruments and our increasingly facile ability to assemble large, complex data sets acquired across several disciplines into an integrated representation of neural function at the molecular, cellular, and systemic levels. This mini-review has been designed to communicate the principal technical advances and current issues of importance in neuropathology research today in the context of our traditional neuropathology practices. Specific topics briefly addressed in this paper include correlative biology of the many facets of the nervous system; conventional and novel methods for investigating neural structure and function; theoretical and technical issues associated with investigating neuropathology end points in emerging areas of concern (developmental neurotoxicity, neurodegenerative conditions); and challenges and opportunities that will face pathologists in this field in the foreseeable future. We have organized this information in a manner that we hope will be of interest not only to professionals with a career focus in neuropathology, but also to general pathologists who occasionally face neuropathology questions.

Blast TBI Models, Neuropathology, and Implications for Seizure Risk

“…Artifacts can be caused by improper tissue handling that, many times, are unavoidable ( 109 ) but following current guidelines could help to overcome these potential technical issues. Nevertheless, some of them are worth mentioning ( 110 , 111 ). Microscopically, underperfused brain tissues demonstrate collapsed microvessels containing blood, with tissue retraction around them and dark, basophilic neurons are readily observable.…”

“…These artifacts make histological interpretations difficult. Not all parts of the brain will necessarily be evenly well-perfused, but a good perfusion should produce distended vessels throughout the brain with no or minimal artifacts ( 110 , 111 ).…”

“…Dendrites often have a characteristic cork-screw shaped appearance. Such neurons are more frequent in immersion-fixed brains but adequately perfused material can still contain numerous dark neurons in experimental neuropathology ( 110 , 111 , 116 , 117 ). Mechanical post-mortem manipulation of the brain can increase the number of these neurons ( 110 , 118 ).…”

STP Position Paper: Recommended Best Practices for Sampling, Processing, and Analysis of the Peripheral Nervous System (Nerves and Somatic and Autonomic Ganglia) during Nonclinical Toxicity Studies

“…For scenarios in which PNS neurotoxicity is suspected (situations 2 and 3) or likely (situation 4), or where regulatory guidelines require plastic embedding of nerve (EPA 1998a), selected nerve samples require additional fixation to adequately stabilize lipids in myelin. For this purpose, one (situations 2 and 3) or at least two (situation 4) nerves—usually spinal-origin somatic trunks rather than autonomic branches—are postfixed in MGG and then osmium tetroxide 12 (Bolon et al 2008; Raimondo et al 2009). Osmium must be used with glutaraldehyde to best maintain cellular structures (Penttila, Kalimo, and Trump 1974).…”

Nervous system

“…Additional histochemistry stains, which include Amino cupric silver (ACS) or fluorojade (FJ), are considered to help confirm an H&E diagnosis and provide an increased contrast and sensitivity to discriminate between affected and nonaffected neurons (for example where degenerate neurons are sparse). Fluorojade (either B or C) works on FFPE tissue following immersion fixation but it is important to note that red blood cells (in immersion fixed or poorly perfused tissues) will also fluoresce green with FJ (Bolon et al 2008;Jordan et al 2011). Fluorojade (either B or C) works on FFPE tissue following immersion fixation but it is important to note that red blood cells (in immersion fixed or poorly perfused tissues) will also fluoresce green with FJ (Bolon et al 2008;Jordan et al 2011).…”