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Developmental Analysis of Chlorambucil‐Induced Occipital Blebs in Mice
Author(s) -
SEKIMOTO Hiroshi,
HATTA Toshihisa,
MORIYAMA Kenji,
OTANI Hiroki,
MORITAKE Kouzo,
TANAKA Osamu
Publication year - 1997
Publication title -
congenital anomalies
Language(s) - English
Resource type - Journals
eISSN - 1741-4520
pISSN - 0914-3505
DOI - 10.1111/j.1741-4520.1997.tb00546.x
Subject(s) - neuroepithelial cell , neural tube , meninges , anatomy , bleb (medicine) , pathology , biology , embryo , medicine , neural stem cell , microbiology and biotechnology , glaucoma , neuroscience , stem cell , trabeculectomy
SUMMARY This study was designed to examine whether defects of the meningeal anlage and intracranial hydrodynamic overload are involved in the pathogenesis of secondary cranioschisis after the neural tube closure. Chlorambucil (CA) 3.0–4.0 mg/kg administered to pregnant mice on day 7.5 of gestation (E7.5) caused abnormal blebs at the occipital region of embryos on E13.5 in a dose‐dependent fashion compared with control. At blebs, the mesencephalic ventricle was dilated, particularly on the dorsal midline and posterior to the pineal invagination. Histology showed fewer mesenchymal cells and vessels, as well as thinner neuroepithelial tissue than in controls. Transmission electron microscopy revealed that the cytoplasm of mesenchymal cells in the bleb region contained abnormal electron‐dense deposits, whereas deposits or other subcellular abnormalities were not evident in either the neuroepithelium or the surface ectoderm of the affected region. We administered 3.5 mg/kg of CA on E7.5 and studied the embryonic development. Mesodermal hypoplasia appeared on E11.5, whereas blebs were initially recognized on E13.5. On E15.5 and E18.5, the meninges and calvaria were hypoplastic, although no apparent cranioschisis was evident. To examine whether increased intracranial hydrodynamic pressure plus defects in the anlage of the meninges and cranium induces secondary cranioschisis, we injected kaolin into the cerebral ventricle on E13.5 to induce hydrocephaly. These embryos developed exo utero and we examined the morphology on E18.5. Hydrocephaly was induced and the defects were more severe in the meninges and cranium than in embryos exposed to CA alone, although cranioschisis was not histologically confirmed. These results suggested that hypoplasia in the mesoderm during early organogenesis underlies later abnormalities of the meninges and cranium, which may be involved in the pathogenesis of certain types of cranioschisis.