Summary
Segmentation of the cerebral cortex with formation of nodules, predominating in the upper cortical levels, was found in the rat after 200 cGy X-ray exposure at embryonic days 15, 17 or 19. Nodules were composed of pyramidal and nonpyramidal neurons occupying normal positions at different levels of the cerebral cortex as revealed with parvalbumin and calbindin D-28k immunocytochemistry. The nodules, which were large in animals irradiated at embryonic day 15 but reduced to groups of a few cells in rats irradiated at embryonic day 19, were separated by low cell density zones. Autoradiographic studies using tritiated methylthymidine injections given to pregnant irradiated rats at different days of gestation further demonstrated a preserved inside-out gradient of cortical neurogenesis in this cortical malformation. Morphological studies of irradiated embryos disclosed that groups of dead cells were separated by patches of preserved cells in the germinal layer 6 h after irradiation. Columns of migrating neuroblats separated by low cell density zones were seen 24 h later. These features suggest that cortical nodules observed after prenatal X-irradiation were the result of multifocal cell death in vulnerable (at the moment of X-ray exposure) proliferative units of the germinal neuroepithelium, combined with normal neurogenesis and migration of neuroblats from the preserved germinal zones. These findings also suggest that cell proliferation is not uniform through the germinal layer but occurs synchronously in alternate proliferative units. These proliferative units probably co-generate pyramidal and nonpyramidal cells.
Similar content being viewed by others
References
Altman J, Bayer SA (1990) Vertical compartmentation and cellular transformation in the germinal matrices of the embryonic rat cerebral cortex. Exp Neurol 107:23–35
Amaral DG, Insausti R (1990) Hippocampal formation. In: Paxinos G (ed) The human nervous system. Academic Press, New York, pp 711–755
Berry M, Eayrs JT (1966) The effects of X-irradiation on the development of the cerebral cortex. J Anat 100:707–722
Berry M, Rogers AW (1965) The migration of neuroblast in the developing cerebral cortex. J Anat 99:691–709
Berry M, Rogers AW, Eayrs JT (1964) Pattern of cell migration during cortical histogenesis. Nature 203:591–593
Blümcke I, Hof PR, Morrison JH, Celio MR (1990) Distribution of parvalbumin immunoreactivity in the visual cortex of the old world monkeys and humans. J Comp Neurol 301:417–432
Celio MR (1986) Parvalbumin in most gamma-aminobutyric acid-containing neurons of the rat cerebral cortex. Science 231:995–997
Celio MR (1990) Calbindin D-28k and parvalbumin in the rat nervous system. Neuroscience 35:375–475
DeFelipe J, Hendry SHC, Jones EG (1989) Visualization of chandelier cell axons by parvalbumin immunoreactivity in monkey cerebral cortex. Proc Natl Acad Sci USA 86:2093–2097
DeFelipe J, Hendry SHC, Jones EG (1989) Synapses of double-bouquet cells in monkey cerebral cortex visualized by calbindin immunoreactivity. Brain Res 503:49–54
DeFelipe J, Hendry SHC, Hashikawa T, Molinari M, Jones EG (1990) A microcolumnar structure of monkey cerebral revealed by immunocytochemical studies of double bouquet cell axons. Neuroscience 37:655–673
Demeulemeester H, Orban GA, Brandon C, Vanderhaeghen JJ (1988) Heterogeneity of GABAergic cells in the cat visual cortex. J Neurosci 8:988–1000
Demeulemeester H, Vandesande F, Orban GA, Heizmann CW, Pocher R (1989) Calbindin D-28k and parvalbumin immunoreactivity is confined to two separate neuronal subpopulations in the cat visual cortex, whereas partial coexistence is shown in the dorsal geniculate nucleus. Neurosci Lett 9:6–11
Demeulemeester H, Arckness L, Vandesande F, Ornan GA, Heizmann W, Pochet R (1991) Calcium binding proteins and neuropeptides as molecular markers of GABAergic interneurons in the cat visual cortex. Exp Brain Res 84:538–544
Eccles JC (1984) The cerbral cortex: a theory of its operation. In: Jones EG, Peters A (eds) Cerebral cortex, vol 2. Plenum Press, London, pp 1–36
Ferrer I, Xumetra A, Santamaría J (1984) Cerebral malformation induced by prenatal X-irradiation: an autoradiographic and Golgi study. J Anat 138:81–93
Ferrer I, Tuñón T, Soriano E, del Rio A, Iraizoz I, Fonseca M, Guionnet N (1992) Calbindin immunoreactivity in normal human temporal neocortex. Brain Res 572:33–41
Friede RL (1989) Developmental neuropathology. Springer Verlag, Berlin Heidelberg New York Tokyo, pp 99–301
Hendry SH, Jones EG, Emson DC, Lawson DE, Heizmann CW, Streit P (1989) Two classes of cortical GABA neurons defined by differential calcium binding protein immunoreactivities. Exp Brain Res 76:467–472
Hicks SP (1958) Radiation as an experimental tool in mammalian developmental neurology. Physiol Rev 38:337–356
Hicks SP, D'Amato CJ (1966) Effects of ionizing radiations on mammalian development. In: Woollam DH (ed) Advances in teratology. Logos Press, London, pp 195–250
Hicks SP, D'Amato CJ (1968) Cell migration to the isocortex in the rat. Anat Rec 160:619–634
Hicks SP, D'Amato CJ (1978) Effects of ionizing radiation on developing brain and behavior. In: Gottlieb G (ed) Studies of the development of behavior and the nervous system, vol 4. Academic Press, New York, pp 35–72
Hicks SP, D'Amato CJ, Lowe MJ (1959) The development of the mammalian nervous system. J Comp Neurol 113:435–469
Jensen KF, Altman J (1982) The contribution of late-generated neurons to the callosal projection in the rat: a study with prenatal X-irradiation. J Comp Neurol 209:113–122
Kosaka T, Heizmann CW (1989) Selective staining of a population of parvalbumin-containing GABAergic neurons in the cerebral cortex by lectins with specific affinity for terminal N-acetylgalactosamine. Brain Res 483:158–163
Kosaka T, Katsumaru H, Hama K, Wu JY, Heizmann CW (1987) GABAergic neurons containing the Ca2+ binding protein parvalbumin in the rat hippocampus and denate gyrus. Brain Res 419:119–130
Kosaka T, Heizmann CW, Barnstable CJ (1989) Monoclonal antibody VC1.1 selectively stains a population of GABAergic neurons containing the calcium-binding protein parvalbumin in the rat cerebral cortex. Exp Brain Res 78:43–50
Kosaka T, Isogai K, Barnstable CJ, Heizmann CW (1990) Monoclonal antibody HNK-1 selectively stains a subpopulation of GABAergic neurons containing the calcium-binding protein parvalbumin in the rat cerebral cortex. Exp Brain Res 82:566–574
Lewis DA, Lund JS (1990) Heterogeneity of chandelier neurons in monkey neocortex: corticotropin-releasing factor and parvalbumin-immunoreactive populations. J Comp Neurol 293:599–615
Miller MW (1985) Co-generation of retrogradely labeled corticocortical projection and GABA-immunoreactive local circuit neurons in neocortex. Dev Brain Res 23:187–192
Miller MW (1988) Development of projection and local circuit neurons in neocortex. In: Peters A, Jones EG (eds) Cerebral cortex, vol 7. Plenum Press, New York, pp 133–175
Mizuguchi M, Morimatsu Y (1989) Histopathological study of alobar holoprosencephaly. 1. Abnormal laminar architecture of the telencephalic cortex. Acta Neuropathol 78:176–182
Nitsch R, Soriano E, Frotscher M (1990) The parvalbumin-containing nonpyramidal neurons in the rat hippocampus. Anat Embryol (Berl) 181:413–425
Raedler E, Raedler A (1978) Autoradiographic study of early neurogenesis in rat neocortex. Anat Embryol (Berl) 154:267–284
Rakic P (1988) Specification of cerebral cortical areas. Science 241:170–176
Schmidt SL, Lent R (1987) Effects of prenatal irradiation on the development of cerebral cortex and corpus callosum of the mouse. J Comp Neurol 264:193–204
Sidman RL (1970) Autoradiographic methods and principles for study of the nervous system with thymidyne-H3. In: Nauta JH, Ebbesson SOE (eds) Contemporary research methods in neuroanatomy. Springer Verlag, Berlin Heidelberg New York Tokyo, pp 252–274
Soriano E, Nitsch R, Frotscher M (1990) Axo-axonic chandelier cells in the rat fascia dentata: Golgi-electron microscopy and immunocytochemical studies. J Comp Neurol 293:1–25
Stichel CC, Singer W, Heizmann CW, Norman AW (1987) Immunohistochemical localization of calcium-binding proteins, parvalbumin and calbindin D-28k, in the adult and developing visual cortex of cats: a light and electron microscopic study. J Comp Neurol 262:563–577
van Brederode JFM, Mulligan KA, Hendrickson AE (1990) Calcium-binding proteins as markers for subpopulations of GABAergic neurons in monkey striate cortex. J Comp Neurol 298:1–22
van Brederode JFM, Helliesen MK, Hendrickson AE (1991) Distribution of the calcium-binding proteins parvalbumin and calbindin D-28k in the sensorimotor cortex of the rat. Neuroscience 44:157–171
Yakovlev PJ (1959) Pathoarchitectonic studies of cerebral malformations. III. Arrinencephalies (Holoprosencephalies). J Neuropathol Exp Neurol 18:22–55
Author information
Authors and Affiliations
Additional information
Supported by the CEC Programme B17-0003-C and by a grant FIS 90E1263
Rights and permissions
About this article
Cite this article
Ferrer, I., Alcántara, S., Zújar, M.J. et al. Structure and pathogenesis of cortical nodules induced by prenatal X-irradiation in the rat. Acta Neuropathol 85, 205–212 (1993). https://doi.org/10.1007/BF00227769
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00227769