Harmonization of diagnostic nomenclature used in the pathology analysis of tissues from rodent toxicity studies will enhance the comparability and consistency of data sets from different laboratories worldwide. The INHAND Project (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) is a joint initiative of four major societies of toxicologic pathology to develop a globally recognized nomenclature for proliferative and nonproliferative lesions in rodents. This article recommends standardized terms for classifying changes observed in tissues of the mouse and rat central (CNS) and peripheral (PNS) nervous systems. Sources of material include academic, government, and industrial histopathology databases from around the world. Covered lesions include frequent, spontaneous, and aging-related changes as well as principal toxicant-induced findings. Common artifacts that might be confused with genuine lesions are also illustrated. The neural nomenclature presented in this document is also available electronically on the Internet at the goRENI website (http://www.goreni.org/).

Interest has developed in using magnetic resonance (MR) imaging to monitor the volume of tissue destroyed by interstitial laser photocoagulation (ILP). In these experiments, ILP was induced in the normal brains of 9 anesthetized cats by delivering 1.5 W of continuous-wave Nd:YAG laser energy (1,064 nm) from a single 400-microns core optical fiber for 1,000 s. The irradiations were monitored using proton spin-echo MR imaging during and immediately after ILP and at postirradiation survival times of 2, 5, and 14 days. At 2 days postirradiation, the necrotic thermal lesion consisted of a central cavity surrounded by 2 concentric zones of coagulative necrosis, one dense and the other dispersed. The lesion shrank and the zonal appearance became less obvious over the 14 day survival period. An enhancing halo on contrast-enhanced T1-weighted images acquired immediately postirradiation best approximated the total lesion diameter at 2 days. These images also indicated that the volume of tissue destroyed during ILP corresponded better to the necrotic volume determined at 2 days than at 5 days and 14 days postirradiation. T2-weighted images acquired during and immediately after ILP consistently underestimated the total lesion diameter at 2 days.

This article outlines the changes and underlying rationale for modifications to the histopathological evaluation of the nervous system during toxicology and carcinogenesis studies conducted by the National Toxicology Program (NTP). In the past, routine evaluation of the nervous system was mostly limited to three sections of brain, and occasionally the spinal cord and peripheral nerves. Factors such as the increasing occurrence of human neurological diseases and associated economical cost burden, the role of unidentified environmental stressors in neurodegenerative disorders, multiple therapeutic drug-induced neuropathies noted in human clinical trials, and the exponential use of environmental chemicals with unknown neurotoxic potential necessitate a more extensive evaluation of the nervous system. The NTP has modified its protocol to include examination of key anatomic subsites related to neurodegenerative diseases such as Parkinson's disease. Modifications include four additional sections of the brain. Increasing the number of brain sections permits examination of a greater number of specific anatomic subsites with unique vulnerability. In addition, the spinal cord, peripheral nerves, trigeminal ganglion, and intestinal autonomic ganglia will be evaluated as needed. It is expected that this modified approach will increase the sensitivity of detecting neurotoxicants and neurocarcinogens important in human neurologic and neurodegenerative disorders.Keywords: neuropathology; histopathology; brain; nervous system; NTP; nervous system; screening.Since its inception in 1978, one of the major goals of the National Toxicology Program (NTP) has been to identify carcinogens (based on carcinogenicity for laboratory animals under conditions of study as adopted by NTP since 1983) based on 2-year rodent bioassays. The standard three sections of the brain examined in such routine studies were taken at the levels of (1) the basal ganglia, including the cerebrum at the frontal cortical level; (2) the thalamus at the mid-infundibular level; and (3) a mid-cerebellar section that included the cerebellum and medulla. For studies in which clinical neurological signs were noted, or studies in which agents were suspected to be neurotoxic, sections of the spinal cord and the sciatic nerve were also examined. In addition to the identification of carcinogens, the NTP has recently started a number of initiatives to assess adverse, nonneoplastic toxicological effects. Since environmental factors that affect nonneoplastic conditions such as immune-mediated diseases (Virgolini et al. 2005) and reproductive disorders (Davey et al. 2008) are increasingly common, initiatives within the NTP have included enhanced immunopathology as well as revised criteria for histopathological evaluation in reproductive and developmental toxicity studies. Similarly, increasing attention to the role of environmental factors in neurological disorders such as Parkinson's disease ) and autism (Cavagnaro 2007) also emphasizes the need for improved toxicity e...

Harmonization of diagnostic terminology used during the histopathologic analysis of rodent tissue sections from nonclinical toxicity studies will improve the consistency of data sets produced by laboratories located around the world. The INHAND Project ( International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) is a cooperative enterprise of 4 major societies of toxicologic pathology to develop a globally accepted standard vocabulary for proliferative and nonproliferative lesions in rodents. A prior manuscript ( Toxicol Pathol 2012;40[4 Suppl]:87S-157S) defined multiple diagnostic terms for toxicant-induced lesions, common spontaneous and age-related changes, and principal confounding artifacts in the rat and mouse central nervous system (CNS) and peripheral nervous system (PNS). The current article defines 9 new diagnostic terms and updates 2 previous terms for findings in the rodent CNS and PNS, the need for which has become evident in the years since the publication of the initial INHAND nomenclature for findings in rodent neural tissues. The nomenclature presented in this document is also available electronically on the Internet at the goRENI website ( http://www.goreni.org/ ).