|
Sign In to gain access to subscriptions and/or personal tools.
|
Evaluation of Large-Sized Brains for Neurotoxic Endpoints
Robert H. Garman
Consultants in Veterinary Pathology, Inc, Murrysville, Pennsylvania 15668-0068
Sampling of large-sized brains (eg, dog, primate) for microscopic examination is frequently inadequate to detect localized neurotoxic injury. Furthermore, the examination of H&E-stained sections alone will often be insufficient for the detection of subtle neuropathogic alteration. It is imperative for any pathologist evaluating brain sections to have knowledge of microscopic neuroanatomy and to also have some understanding of basic neurochemistry. When a focus of degeneration is detected within the brain, the pathologist needs to ascertain not only the specific anatomic location of this focus but also the neuroanatomic regions that project to and receive output from the injured focus. Because of the complexity of brain circuitry and the fact that the brain contains many distinctive neuron populations, many more brain sections are required for adequate microscopic evaluation than for any other body organ. Deciding which and how many areas should be examined, microscopically, from a large size brain is often problematic. Although any sampling protocol will be influenced by what is known about the test chemical, it has been well established that certain regions of the brain (eg, hippocampus and other components of the limbic system, basal ganglia, Purkinje neurons) are more susceptible than others to a variety of physical, metabolic, and chemical insults. Knowledge of these regional sensitivities will assist in guiding the pathologist in the development of an adequate sampling protocol.
Key Words: Brain • cupric silver stain • dog • Fluoro-Jade stain • neuroanatomy • neuropathology • neurotoxicity.
References
- Bolon B. (2000). Comparative and correlative neuroanatomy for the toxicologic pathologist. Toxicol Pathol 28: 6—27.[Abstract/Free Full Text]
- de Olmos JD, Beltramino CA, de Olmos-de Lorenzo S. (1994). Use of an amino-cupric silver technique for the detection of early and semiacute neuronal degeneration caused by neurotoxicants, hypoxia, and physical trauma. Neurotoxicol Teratol 16: 545—561.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Dua-Sharma S., Sharma S., Jacobs HL (1970). The Canine Brain in Stereotaxic Coordinates, MIT Press, Cambridge, Massachusetts.
- Fix AS, Garman RH (2000). Practical aspects of neuropathology: A technical guide for working with the nervous system. Toxicol Pathol 28: 122— 131.[Abstract/Free Full Text]
- Fix AS, Horn JW, Wightman KA, Johnson CA, Long GG, Storts RW, FarberN., WozniakDF, Olney JW (1993). Neuronal vacuolization and necrosis induced by the noncompetitive N-methyl-D-aspartate (NMDA) antagonist MK(+)801 (Dizocilpine Maleate): A light and electron microscopic evaluation of the rat retrosplenial cortex. Exper Neurol 123: 204—215.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Garman RH (1990). Artifacts in routinely immersion fixed nervous tissue. Toxicol Pathol 18: 149—153.[Web of Science][Medline]
[Order article via Infotrieve]
- Ikonomidou C., Bosch F., Miksa M., Bittigau P., Vöckler J., Dikranian K., Tenkova TI, Stefovska V., Turski L., Olney JW (1999). Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science 283: 70—74.[Abstract/Free Full Text]
- Jenkins TW( 1972). Functional Mammalian Neuroanatomy. Lea & Febiger, Philadelphia.
- Kim RKS, Liu CN, Moffitt RL (1960). A Stereotaxic Atlas of the Dog's Brain, Charles C Thomas, Springfield, Illinois.
- Kofke WA, Ataallah AF, Kuwabara H., Garman RH, Sinz EH, Barbaccia JB, Gupta N., Hogg JP ( 2002). Neuropathologic effects in rats and neurometabolic effects in humans of high-dose remifentanil. Anesthesia Analgesia 94: 1229—1236.[Abstract/Free Full Text]
- Li Q., Clark S., Lewis DV, Wilson WA (2002). NMDA receptor antagonists disinhibit rat posterior cingulate and retrosplenial cortices: A potential mechanism of neurotoxicity. J Neurosci 22: 3070— 3080.[Abstract/Free Full Text]
- Olney JW, Ishimaru MJ (1999). Excitotoxic cell death. In: Cell Death and Diseases of the Nervous System, Koliatsos VE, Ratan RR (eds). Humana Press, Totowa, New Jersey, pp 197—219.
- Schmued LC, Hopkins KJ( 2000). Fluoro-Jade B: Ahigh affinity fluorescent marker for the localization of neuronal degeneration. Brain Res 874: 123— 130.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Schmued LC, Hopkins KJ (2000). Fluoro-Jade: Novel fluorochromes for detecting toxicant-induced neuronal degeneration. Toxicol Pathol 28: 91— 99.[Abstract/Free Full Text]
- Singer M. (1962). The Brain of the Dog in Section, WB Saunders Company, Philadelphia, Pennsylvania.
- Spencer PS (2000). Biological principles of chemical neurotoxicity. In: Experimental and Clinical Neurotoxicology, Spencer PS, Schaumburg HH, Ludolph AC (eds). Oxford University Press, New York, pp 3—54.
- Switzer RC (1993). Silver staining methods: Their role in detecting neurotoxicity. Markers of Neuronal Injury and Degeneration, NYAS, Volume 679, pp 341—348.
- Switzer RC (2000). Application of silver degeneration stains for neurotoxicity testing. Toxicol Pathol 28: 70—83.[Abstract/Free Full Text]
- Yehezkel BA, Roustem K., Leinekugel X., Caillard O., Gaiarsa JL (1997). GABAA, NMDA and AMPA receptors: A developmentally regulated `ménage à trois.' TINS 20: 523—529.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
Toxicologic Pathology, Vol. 31, No. 1 suppl,
32-43 (2003)
DOI: 10.1080/01926230390174913
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
B. Bolon, D. C. Anthony, M. Butt, D. Dorman, M. V. Green, P. B. Little, W. M. Valentine, D. Weinstock, J. Yan, and R. C. Sills
"Current Pathology Techniques" Symposium Review: Advances and Issues in Neuropathology
Toxicol Pathol,
October 1, 2008;
36(6):
871 - 889.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
