The Nervous System

  • Chirukandath Gopinath
  • Vasanthi Mowat


The importance of correct and adequate sampling of central nervous system in laboratory animals is stressed. Lesions pertaining to neurons such as necrosis, loss, and vacuolation are illustrated. Neuronal changes affecting the cerebrum and cerebellum are included. Distal and proximal axonopathies with examples are described with representative figures. Other changes discussed include demyelination, myelin oedema, and inflammatory lesions in different laboratory animals. Changes occurring in glial cells and choroid plexus are also described. A brief section on induced gliomas in rats is also included.


Dorsal Root Ganglion Glial Fibrillary Acidic Protein Carbon Disulphide Myelin Damage Distal Axonopathies 
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  1. 1.
    Garman RH. Evaluation of large-sized brains for neurotoxic endpoints. Toxicol Pathol. 2003;31(Suppl):32–43.PubMedCrossRefGoogle Scholar
  2. 2.
    Jordan WH, Young JK, Hyten MJ, Hall DG. Preparation and analysis of the central nervous system. Toxicol Pathol. 2011;39:58–65.PubMedCrossRefGoogle Scholar
  3. 3.
    Garman RH, Fix AS, Jortner BS, Jensen KF, Hardisty JF, Claudio L, et al. Methods to identify and characterize developmental neurotoxicity for human health risk assessment. II: neuropathology. Environ Health Perspect. 2001;109 Suppl 1:93–100.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Switzer III RC, Lowry-Franssen C, Benkovic SA. Recommended neuroanatomical sampling practices for comprehensive brain evaluation in nonclinical safety studies. Toxicol Pathol. 2011;39:73–84.PubMedCrossRefGoogle Scholar
  5. 5.
    Jortner BS. Preparation and analysis of the peripheral nervous system. Toxicol Pathol. 2011;39:66–72.PubMedCrossRefGoogle Scholar
  6. 6.
    Jortner BS. Mechanisms of toxic injury in the peripheral nervous system: neuropathologic considerations. Toxicol Pathol. 2000;28:54–69.PubMedCrossRefGoogle Scholar
  7. 7.
    Switzer II RC. Application of silver degeneration stains for neurotoxicity testing. Toxicol Pathol. 2000;28:70–83.PubMedCrossRefGoogle Scholar
  8. 8.
    Hale SL, Andrews-Jones L, Jordan WH, Jortner BS, Boyce RW, Boyce JT, et al. Modern pathology methods for neural investigations. Toxicol Pathol. 2011;39:52–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Kaufmann W, Bolon B, Bradley A, Butt M, Czasch S, Garman RH, et al. Proliferative and nonproliferative lesions of the rat and mouse central and peripheral nervous systems. Toxicol Pathol. 2012;40:87S–157.PubMedCrossRefGoogle Scholar
  10. 10.
    Garman RH. Histology of the central nervous system. Toxicol Pathol. 2011;39:22–35.PubMedCrossRefGoogle Scholar
  11. 11.
    Farina M, Rocha JB, Aschner M. Mechanisms of methylmercury-induced neurotoxicity: evidence from experimental studies. Life Sci. 2011;89:555–63.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Sakamoto M, Kakita A, de Oliveira RB, Sheng PH, Takahashi H. Dose-dependent effects of methylmercury administered during neonatal brain spurt in rats. Brain Res Dev Brain Res. 2004;152:171–6.PubMedCrossRefGoogle Scholar
  13. 13.
    Chang LW. The neurotoxicology and pathology of organomercury, organolead, and organotin. J Toxicol Sci. 1990;15 Suppl 4:125–51.PubMedCrossRefGoogle Scholar
  14. 14.
    Sorensen FW, Larsen JO, Eide R, Schionning JD. Neuron loss in cerebellar cortex of rats exposed to mercury vapor: a stereological study. Acta Neuropathol. 2000;100:95–100.PubMedCrossRefGoogle Scholar
  15. 15.
    McCann MJ, O’Callaghan JP, Martin PM, Bertram T, Streit WJ. Differential activation of microglia and astrocytes following trimethyl tin-induced neurodegeneration. Neuroscience. 1996;72:273–81.PubMedCrossRefGoogle Scholar
  16. 16.
    Barone Jr S. Developmental differences in neural damage following trimethyl-tin as demonstrated with GFAP immunohistochemistry. Ann N Y Acad Sci. 1993;679:306–16.PubMedCrossRefGoogle Scholar
  17. 17.
    Chung JY, Choi JH, Hwang CY, Youn HY. Pyridoxine induced neuropathy by subcutaneous administration in dogs. J Vet Sci. 2008;9:127–31.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Krinke G, Schaumburg HH, Spencer PS, Suter J, Thomann P, Hess R. Pyridoxine megavitaminosis produces degeneration of peripheral sensory neurons (sensory neuronopathy) in the dog. Neurotoxicology. 1981;2:13–24.PubMedGoogle Scholar
  19. 19.
    Riljak V, Milotova M, Jandova K, Langmeier M, Maresova D, Pokorny J, et al. Repeated kainic acid administration and hippocampal neuronal degeneration. Prague Med Rep. 2005;106:75–8.PubMedGoogle Scholar
  20. 20.
    Lavoie B, Parent A, Bedard PJ. Effects of dopamine denervation on striatal peptide expression in parkinsonian monkeys. Can J Neurol Sci. 1991;18:373–5.PubMedGoogle Scholar
  21. 21.
    Peltier AC, Russell JW. Recent advances in drug-induced neuropathies. Curr Opin Neurol. 2002;15:633–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Genovese RF, Newman DB. Understanding artemisinin-induced brainstem neurotoxicity. Arch Toxicol. 2008;82:379–85.PubMedCrossRefGoogle Scholar
  23. 23.
    Mimaki T, Deshmukh PP, Yamamura HI. Decreased benzodiazepine receptor density in rat cerebellum following neurotoxic doses of phenytoin. J Neurochem. 1980;35:1473–5.PubMedCrossRefGoogle Scholar
  24. 24.
    Greaves P. Nervous system and special sense organs. In: Greaves P, editor. Histopathology of preclinical toxicity studies. Amsterdam: Elsevier; 2012. p. 799–866.CrossRefGoogle Scholar
  25. 25.
    Dowson JH, Wilton-Cox W, James NT. Lipopigment in rat hippocampal and Purkinje neurones after chronic phenytoin administration. J Neurol Sci. 1992;107:105–10.PubMedCrossRefGoogle Scholar
  26. 26.
    Akasaki Y, Takauchi S, Miyoshi K. Cerebellar degeneration induced by acetyl-ethyl-tetramethyl-tetralin (AETT). Acta Neuropathol. 1990;80:129–37.PubMedCrossRefGoogle Scholar
  27. 27.
    Sterman AB, Spencer PS. The pathogenesis of primary internodal demyelination produced by acetyl ethyl tetramethyl tetralin: evidence for preserved Schwann cell somal function. J Neuropathol Exp Neurol. 1981;40:112–21.PubMedCrossRefGoogle Scholar
  28. 28.
    Schaumburg HH, Spencer PS. Toxic models of certain disorders of nervous system—a teaching monograph. Neurotoxicology. 1979;1:209–20.Google Scholar
  29. 29.
    Krinke G, Schaumburg HH, Spencer PS, Thomann P, Hess R. Clioquinol and 2,5-hexanedione induce different types of distal axonopathy in the dog. Acta Neuropathol. 1979;47:213–21.PubMedCrossRefGoogle Scholar
  30. 30.
    Thomas PK. Selective vulnerability of the centrifugal and centripetal axons of primary sensory neurons. Muscle Nerve. 1982;5:S117–21.PubMedGoogle Scholar
  31. 31.
    Llorens J, Crofton KM, O’Callaghan JP. Administration of 3,3′-iminodipropionitrile to the rat results in region-dependent damage to the central nervous system at levels above the brain stem. J Pharmacol Exp Ther. 1993;265:1492–8.PubMedGoogle Scholar
  32. 32.
    Schulze GE, Boysen BG. A neurotoxicity screening battery for use in safety evaluation: effects of acrylamide and 3′,3′-iminodipropionitrile. Fundam Appl Toxicol. 1991;16:602–15.PubMedCrossRefGoogle Scholar
  33. 33.
    Powell HC, Myers RR, Lampert PW. Edema in neurotoxic injury. In: Shaumberg H, Spencer P, editors. Experimental and clinical neurotoxicology. Baltimore: Williams & Wilkins; 1980. p. 118–38.Google Scholar
  34. 34.
    Gopinath C, Prentice DE, Lewis DJ. The nervous system. In: Gopinath C, Prentice DE, Lewis DJ, editors. Atlas of experimental toxicologic pathology. Lancaster: MTP Press; 1987. p. 137–44.CrossRefGoogle Scholar
  35. 35.
    Ellis WG, Bencken E, LeCouteur RA, Barbano JR, Wolfe BM, Jennings MB. Neurotoxicity of amphotericin B methyl ester in dogs. Toxicol Pathol. 1988;16:1–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Yamamoto T, Iwasaki Y, Sato Y, Yamamoto H, Konno H. Astrocytic pathology of methionine sulfoximine-induced encephalopathy. Acta Neuropathol (Berl). 1989;77:357–68.CrossRefGoogle Scholar
  37. 37.
    Jacobs JM, Ford WC. The neurotoxicity and antifertility properties of 6-chloro-6-deoxyglucose in the mouse. Neurotoxicology. 1981;2:405–17.PubMedGoogle Scholar
  38. 38.
    Heywood R, Sortwell RJ, Prentice DE. The toxicity of 1-amino-3-chloro-2-propanol hydrochloride (CL88,236) in the rhesus monkey. Toxicology. 1978;9:219–25.PubMedCrossRefGoogle Scholar
  39. 39.
    Berry PH, MacDonald JS, Alberts AW, Molon-Noblot S, Chen JS, Lo CY, et al. Brain and optic system pathology in hypocholesterolemic dogs treated with a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Am J Pathol. 1988;132:427–43.PubMedCentralPubMedGoogle Scholar
  40. 40.
    Koizumi H, Watanabe M, Numata H, Sakai T, Morishita H. Species differences in vacuolation of the choroid plexus induced by the piperidine-ring drug disobutamide in the rat, dog, and monkey. Toxicol Appl Pharmacol. 1986;84:125–48.PubMedCrossRefGoogle Scholar
  41. 41.
    Gopinath C. Spontaneous brain tumours in Sprague–Dawley rats. Food Chem Toxicol. 1986;24:113–20.PubMedCrossRefGoogle Scholar
  42. 42.
    Nagatani M, Ando R, Yamakawa S, Saito T, Tamura K. Histological and immunohistochemical studies on spontaneous rat astrocytomas and malignant reticulosis. Toxicol Pathol. 2009;37:599–605.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Chirukandath Gopinath
    • 1
  • Vasanthi Mowat
    • 2
  1. 1.Consultant in Toxicology and PathologyCambridgeshireUK
  2. 2.Huntingdon Life SciencesCambridgeshireUK

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