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Link to original content: https://pubmed.ncbi.nlm.nih.gov/24135464
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Review
. 2014;42(3):487-509.
doi: 10.1177/0192623313501893. Epub 2013 Oct 16.

Subsite awareness in neuropathology evaluation of National Toxicology Program (NTP) studies: a review of select neuroanatomical structures with their functional significance in rodents

Deepa B Rao  1 , Peter B Little, Robert C Sills
Affiliations
Review

Subsite awareness in neuropathology evaluation of National Toxicology Program (NTP) studies: a review of select neuroanatomical structures with their functional significance in rodents

Deepa B Rao et al. Toxicol Pathol. 2014.

Abstract

This review article is designed to serve as an introductory guide in neuroanatomy for toxicologic pathologists evaluating general toxicity studies. The article provides an overview of approximately 50 neuroanatomical subsites and their functional significance across 7 transverse sections of the brain. Also reviewed are 3 sections of the spinal cord, cranial and peripheral nerves (trigeminal and sciatic, respectively), and intestinal autonomic ganglia. The review is limited to the evaluation of hematoxylin and eosin-stained tissue sections, as light microscopic evaluation of these sections is an integral part of the first-tier toxicity screening of environmental chemicals, drugs, and other agents. Prominent neuroanatomical sites associated with major neurological disorders are noted. This guide, when used in conjunction with detailed neuroanatomic atlases, may aid in an understanding of the significance of functional neuroanatomy, thereby improving the characterization of neurotoxicity in general toxicity and safety evaluation studies.

Keywords: NTP; brain; functional neuroanatomy.; nerve; neuroanatomy; neuropathology; spinal cord.

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Figures

Figure 1
Figure 1
Rat: H&E. Seven transverse sections corresponding to levels based on anatomic target landmarks. Level 1 is at the mid-level olfactory bulb (OB). Level 2 is approximately 1–2 mm rostral to the optic chiasm (OC). Level 3 is taken at the infundibulum (IF) and/or median eminence. Level 4 corresponds to the superior colliculus, while Level 5 corresponds to inferior colliculus. Level 6 is at the mid-cerebellum, at the root of the eighth or vestibulocochlear cranial nerve (CN VIII). Level 7 is taken 2–3 mm rostral to the caudal termination of the cerebellum. CP = cerebral peduncle. Note: Although not identical, the trimming planes are comparable to the planes depicted in Rao et al, 2011 and Bolon et al, 2013. It is important to note that modest variations in trimming planes are expected variations in brain sampling among animals within a single study, across multiple studies, and among institutions.
Figure 2
Figure 2
Rat: H&E. Seven transverse sections depicting neuroanatomical subsites. Abbreviations in italics below correspond to abbreviations used in the Paxinos rat brain atlas (Paxinos and Watson 2009). Dotted outlines are close approximations and use of an atlas is recommended for accuracy. 5N= motor trigeminal nucleus; 7N = Facial nucleus; 10N = dorsal motor nucleus of vagus; 12N = hypoglossal nucleus; ac = anterior commissure; Acb = accumbens nucleus (area indicated by dotted line); Amg = amygdaloid nuclei; An = ansiform lobe; AP = area postrema; Au = Auditory (temporal) cortex; cc = corpus callosum; Cg = cingulate cortex; Co= cochlear nucleus; cp = cerebral peduncle; CPu = caudate putamen; DG = dentate gyrus; Ent = entorhinal cortex; EPl = external plexiform layer; FrPt = frontoparietal cortex; Gl = glomerular layer; GrO = granule cell layer; Hb = habenular nucleus; Hipp = hippocampus; HyTh = hypothalamus; IC = inferior colliculus; ic = internal capsule; IO = inferior olivary nucleus; IPl = internal plexiform layer; LC = locus coeruleus; Li = lingula (1st cerebellar lobule or 1Cb); Me5 = mesencephalic trigeminal nucleus; MGB = medial geniculate body; och = optic chiasm; ON = olfactory nerve layer; lo = lateral olfactory tract; PAG = periaqueductal gray; PFl = paraflocculus; Pir = piriform cortex; Pr 5 = principal sensory nucleus of CN V; py = pyramidal tract; R = red nucleus; Rt = reticular formation; RN = raphe nuclei; RS = retrosplenial cortex; SN = substantia nigra; SO = superior olivary nucleus; SpN = septal nuclei; Sol = solitary tract nucleus; sp5 = spinal trigeminal tract; SuC = superior colliculus; Th = thalamus; V = visual (occipital) cortex; Ve = vestibular nucleus; Vr = vermis
Figure 3
Figure 3
Rat: H&E. Transverse section at NTP7, Level 1. (EPl = external plexiform layer; Gl = glomerular layer; GrO = granule cell layer; ON = olfactory nerve layer)
Figure 4
Figure 4
Rat: H&E. Transverse section at NTP-7, Level 2. Dotted lines in Figure 4A and 4E depict the general area of the accumbens nucleus.
Figure 5
Figure 5
Rat: H&E. Transverse section at NTP-7, Level 3 depicting subsites on a section taken at the mid-point of the infundibulum and/or median eminence. Dotted lines closely approximate the medial and lateral habenular nuclei.
Figure 6
Figure 6
Rat: H&E. Transverse section at NTP-7, Level 4 depicting subsites on a section through the superior colliculus. Dotted outlines are close approximations and an atlas should be consulted for accuracy.
Figure 7
Figure 7
Rat: H&E. Transverse section at NTP-7, Level 5 depicting subsites on a section through the inferior colliculus. Dotted outlines are close approximations and an atlas should be consulted for accuracy.
Figure 8
Figure 8
Rat: H&E. Transverse section at Level 6 depicting subsites on a section through the mid-cerebellum. Dotted outlines are close approximations and an atlas should be consulted for accuracy.
Figure 9
Figure 9
Rat: H&E. Transverse section at Level 7 depicting subsites on a section through the caudal medulla oblongata near the caudal termination of the cerebellum. Dotted outlines are close approximations and an atlas should be consulted for accuracy.
Figure 10
Figure 10
Rat: H&E. Transverse sections of the spinal cord through the first cervical, midthoracic, and mid-lumbar levels. (cun fas = cuneate fasciculus; gr fas = gracile fasciculus; dorsolateral fas = dorsolateral fasciculus)
Figure 11
Figure 11
Rat: H&E. Sections through the sciatic nerve. Figure A is a transverse section through the sciatic nerve depicting the outer connective tissue layers (epineurium and perineurium) around a nerve fiber bundle. Inset reveals individual nerve fibers in transverse section showing central axons and surrounding myelin. Figure B is a longitudinal section through the sciatic nerve showing myelin around the axon. A few scattered mast cells are not uncommon in the peripheral nerves in rats.
Figure 12
Figure 12
Rat: H&E. Trigeminal nerve and the ganglion Figure A: Dorsal view of the cranial cavity (brain removed) revealing the course of the trigeminal nerve and its branches (ophthalmic, maxillary and mandibular branches) and its ganglion, rostrolateral to the pituitary gland. Figure B: A section of the trigeminal ganglion. Ganglion cells at higher magnification are shown in Figure C. (ophthalmic br = ophthalmic branch; maxillary br = maxillary branch; mandibular br = mandibular branch)
Figure 13
Figure 13
Rat: H&E. Colon A transverse section of the colon depicting the location of intestinal autonomic ganglia. (mm = muscularis mucosa; sm = submucosa; mp = muscularis propria)
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