Skip to main content
SpringerLink
Log in

Cytoarchitectonic investigation of the rat spinal cord following ethylnitrosourea administration at different developmental stages

  • Published:
Virchows Archiv A Aims and scope Submit manuscript

Summary

We examined the histological findings and cytoarchitectonic alterations in the rat spinal cord following matrix cell degeneration caused at different developmental stages, from neural plate formation through neuroblast generation. Ethylnitrosourea (ENU) 20 mg/kg body weight was administered transplacentally to the fetuses on the 10th embryonic day (E10) to 14th. The observations were made until the 21st postnatal day. Normally, mitoses were present scatteredly in the matrix cell layer of the neural plate or neural tube on El0 or E11, and gradually restricted to the dorsal portion of the alar plate as development occurred. The localization and number of degenerative cells as well as the site and degree of neuronal decrease in the completed dysgenetic spinal cord seemed to correlate with the topography and frequency of the mitoses in the matrix cell layer at the time of ENU administration. Disorder in the pattern of cytoarchitecture of neurons was not observed. The degree of hypoplasia of the white matter was proportional to the intensity of decrease of the spinal neurons. Aberrant myelinated fibers were not seen. No reactive gliosis, fibrosis or abnormal vascularization was observed at any time.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Altman J, Anderson WJ (1971) Irradiation of the cerebellum in infant rats with low-level X-ray: histological and cytological effects during infancy and adulthood. Exp Neurol 30:492–509

    Google Scholar 

  • Altman J, Bayer SA (1984) The development of the rat spinal cord. Advances in anatomy embryology and cell biology 85. Springer, Berlin Heidelberg New York

    Google Scholar 

  • Altman J, Anderson WJ, Wright KA (1969) Early effects of X-irradiation of the cerebellum in infant rats: decimation and reconstitution of the external granular layer. Exp Neurol 24:196–216

    Google Scholar 

  • Bosch DA (1977a) Short and long term effects of methyl- and ethylnitrosourea (MNU & ENU) on the developing nervous system of the rat. I: Long term effects: the induction of (multiple) gliomas. Acta Neurol Scand 55:85–105

    Google Scholar 

  • Bosch DA (1977b) Short and long term effects of methyl- and ethylnitrosourea (MNU & ENU) on the developing nervous system of the rat. II: Short term effects: concluding remarks on chemical neuro-oncogenesis. Acta Neurol Scand 55:106–122

    Google Scholar 

  • Clarren SK, Hall JG (1983) Neuropathologic findings in the spinal cords of 10 infants with arthrogryposis. J Neurol Sci 58:89–102

    Google Scholar 

  • Cruz AR, Lison L (1963) Nucleo-cytoplasmic allometric relation in some nerve cells. Z Mikrosk Anat Forsch 70:139–167

    Google Scholar 

  • Drachman DB, Banker BQ (1961) Arthrogryposis multiplex congenita. Case due to disease of the anterior horn cells. Arch Neurol 5:89–105

    Google Scholar 

  • Druckrey H, Ivankovic S, Preussmann Zülch KJ, Mennel HD (1972) Selective induction of malignant tumors of the nervous system by resorptive carcinogens. In: Kirsch WM, Grossi-Paoletti E, Paoletti P (eds) The experimental biology of brain tumors. Thomas, Springfield Ill, pp 85–147

  • Ferrer I, Xumetra A, Santamaria J (1984) Cerebral malformation induced by prenatal X-irradiation: an autoradiographic and Golgi study. J Anat 138:81–93

    Google Scholar 

  • Friede RL (1975) Developmental neuropathology. 27. Disturbances in the bulk growth of nervous tissue, 32. Dysplasias of brain stem and spinal cord. Springer, Wien, pp 271–279, pp 339–351

    Google Scholar 

  • Fujita S (1964) Analysis of neuron differentiation in the central nervous system by tritiated thymidine autoradiography. J Comp Neurol 122:311–327

    Google Scholar 

  • Fujiwara H (1980) Cytotoxic effects of ethylnitrosourea on central nervous system of rat embryos. Special references to carcinogenesis and teratogenesis. Acta Pathol Jpn 30:375–387

    Google Scholar 

  • Hallas BH, Das GD (1978) N-ethyl-N-nitrosourea-induced teratogenesis of brain in the rat. A cellular and cytoarchitectural analysis of the neocortex. J Neurol Sci 39:111–122

    Google Scholar 

  • Hicks SP (1953) Developmental malformations produced by radiation. A timetable of their development. AJR 69:272–293

    Google Scholar 

  • Hicks SP, D'Amato CJ, Lowe MJ (1959) The development of the mammalian nervous system. I. Malformations of the brain, especially the cerebral cortex, induced in rats by radiation. II. Some mechanisms of the malformations of the cortex. J Comp Neurol 113:435–469

    Google Scholar 

  • Holtzer H (1951) Reconstitution of the urodele spinal cord following unilateral ablation. Part I. Chronology of neuron regulation. J Exp Zool 117:523–557

    Google Scholar 

  • Houle JD, Das GD (1983) Permanent alterations in the rat spinal cord following prenatal exposure to N-ethyl-N-nitrosourea. Brain Res Bull 10:839–845

    Google Scholar 

  • Ikuta F, Yoshida Y, Ohama E, Oyanagi K, Takeda S, Yamazaki K, Watabe K (1983) Revised pathophysiology on BBB damage: the edema as an ingeniously provided condition for cell motility and lesion repair. Acta Neuropathol (Berl) (Suppl VIII):103–110

    Google Scholar 

  • Ikuta F, Yoshida Y, Ohama E, Oyanagi K, Takeda S, Yamazaki K, Watabe K (1984) Brain and peripheral nerve edema as an initial stage of the lesion repair; revival of the mechanisms of the normal development in the fetal brain. Prog Neurol Res (Japan) 28:599–628

    Google Scholar 

  • Ivankovic S, Druckrey H (1968) Transplacentare Erzeugung maligner Tumoren des Nervensystems. I. Äthylnitrosoharnstoff (ÄNH) an BD IX-Ratten. Z Krebsforsch 71:320–360

    Google Scholar 

  • Jacobson M (1981) Rohon-beard neurons arise from a substitute ancestral cell after removal of the cell from which they normally arise in the 16-cell frog embryo. J Neurosci 1:923–927

    Google Scholar 

  • Kanemitsu A (1971) Relation entre la taille des neurones et leur époque d'apparition dans la moelle épiniére chez le poulet. Etude autoradiographique et caryométrique. Proc Jpn Acad 47:432–437

    Google Scholar 

  • Kanemitsu A (1977) Etude quantitative de la cytoarchitecture dela moelle epiniére chez le chat et le poulet. Proc Jpn Acad 53B:183–188

    Google Scholar 

  • Kanemitsu A, Ikuta F (1977) Etude quantitative des neurones dans la moelle cervicale chez un cas de l'hémisphérectomie cérébrale. Proc Jpn Acad 53B:189–193

    Google Scholar 

  • Kirby ML (1980) Reduction of fetal rat spinal cord volume following maternal morphine injection. Brain Res 202:143–150

    Google Scholar 

  • Kleihues P (1969) Blockierung der DNS-synthese durch N-methyl-N-nitrosoharnstoff in vivo. Arzneim Forsch 19:1041–1043

    Google Scholar 

  • Kleihues P, Patzschke K (1971) Verteilung von N-[14C] Methyl-N-nitrosoharnstoff in der Ratte nach systemischer Applikation. Z Krebsforsch 75:193–200

    Google Scholar 

  • Kleihues P, Magree PN, Austoker J, Cox D, Mathias AP (1973) Reaction of N-methyl-N-nitrosourea with DNA of neuronal and glial cells in vivo. FEBS Lett 32:105–108

    Google Scholar 

  • Koyama T (1970) Erzeugung von Missbildungen im Gehirn durch Methyl-nitroso-harnstoff and Äthyl-nitroso-harnstoff an SD-JCL Ratten. Arch Jpn Chir 39:233–254

    Google Scholar 

  • Ludwin SK, Norman MG (1985) Congenital malformations of the nervous system. In: Davis RL, Robertson DM (eds) Textbook of neuropathology. Williams&Wilkins, Baltimore, pp 229–231

    Google Scholar 

  • Mannen H (1966) Contribution to the quantitative study of the nervous tissue: A new method for measurement of the volume and surface area of neurons. J Comp Neurol 126:75–90

    Google Scholar 

  • Morrissey RE, Mottet NK (1983) Arsenic-induced exencephaly in the mouse and associated lesions occurring during neurulation. Teratology 28:399–411

    Google Scholar 

  • Nornes HO, Das GD (1974) Temporal pattern of neurogenesis in spinal cord of rat. I. An autoradiographic study - time and sites of origin and migration and settling patterns of neuroblasts. Brain Res 73:121–138

    Google Scholar 

  • Oppenheimer DR (1984) Infantile spinal muscular atrophy of Werdnig and Hoffmann. In: Adams JH, Corsellis JAN, Duchen LW (eds) Greenfield's Neuropathology. 4th edn, Edward Arnold, London, pp 734–737

    Google Scholar 

  • Oyanagi K, Makifuchi T, Ikuta F (1983) A topographic and quantitative study of neurons in human spinal gray matter, with special reference to their changes in amyotrophic lateral sclerosis. Biomed Res 4:211–224

    Google Scholar 

  • Oyanagi K, Yoshida Y, Ikuta F (1986) The chronology of lesion repair in the developing rat brain: biological significance of the pre-existing extra-cellular space. Virchows Arch A 408:347–359

    Google Scholar 

  • Oyanagi K, Takahashi H, Wakabayashi K, Ikuta F (1987) Selective involvement of large neurons in the neostriatum of Alzheimer's disease and senile dementia: a morphometric investigation. Brain Res 411:205–211

    Google Scholar 

  • Phemister RD, Shively JN, Young S (1969) The effects of gamma irradiation on the postnatally developing canine cerebellar cortex. II. Sequential histogenesis of radiation-induced changes. J Neuropathol Exp Neurol 28:128–138

    Google Scholar 

  • Rexed B (1952) The cytoarchitectonic organization of the spinal cord in the cat. J Comp Neurol 96:415–496

    Google Scholar 

  • Rexed B (1954) A cytoarchitectonic atlas of the spinal cord in the cat. J Comp Neurol 100:297–379

    Google Scholar 

  • Schoene WC (1985) Degenerative diseases of the central nervous system. In: Davis RL, Robertson DM (eds) Textbook of Neuropathology, chap. 15. Williams&Wilkins, Baltimore, pp 817–818

    Google Scholar 

  • Smart IHM, Smart M (1982) Growth patterns in the lateral wall of the mouse telencephalon: I. Autoradiographic studies of the histogenesis of the isocortex and adjacent areas. J Anat 134:273–298

    Google Scholar 

  • Watterson RL, Fowler I (1953) Regulative development in lateral halves of chick neural tubes. Anat Rec 117:773–803

    Google Scholar 

  • Wenger EL (1950) An experimental analysis of relations between parts of the brachial spinal cord of the embryonic chick. J Exp Zool 114:51–85

    Google Scholar 

  • Yamano T, Shimada M, Abe Y, Ohta S, Ohno M (1983) Destruction of external granular layer and subsequent cerebellar abnormalities. Acta Neuropathol (Berl) 59:41–47

    Google Scholar 

  • Yoshida Y, Oyanagi K, Ikuta F (1984) Initial cellular damage in the developing rat brain caused by cytotoxicity of ethylnitrosourea. Brain Nerve 36:175–182

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neuropathology, Brain Research Institute, Niigata University, 1 Asahimachi, 951, Niigata, Japan

    Kiyomitsu Oyanagi & Yasuji Yoshida

  2. Department of Pathology, Brain Research Institute, Niigata University, 1 Asahimachi, 951, Niigata, Japan

    Fusahiro Ikuta

Authors
  1. Kiyomitsu Oyanagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yasuji Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fusahiro Ikuta
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This study was supported by a Grant-in-Aid for Scientific Research (A) No. 60440046 from the Ministry of Education, Science and Culture, Japan

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oyanagi, K., Yoshida, Y. & Ikuta, F. Cytoarchitectonic investigation of the rat spinal cord following ethylnitrosourea administration at different developmental stages. Vichows Archiv A Pathol Anat 412, 215–224 (1988). https://doi.org/10.1007/BF00737145

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00737145

Key words

Search

Navigation