The origin of astrocytes of the mouse neocortex during the fetal and early postnatal periods as determined by immunocytological, autoradiographic, electron microscopic and antimitotic methods is described. Most astrocytes destined for the white matter and the infragranular cortical layers are derived from the transformation of radial glial cells between P0 and P10 with an inside-out pattern. This cell metamorphosis is not directly preceded by mitosis and involves the activation of the radial glial lysosomal apparatus. In opposition to recent hypotheses, our findings suggest that most astroyctes destined for the supragranular cortical layers are produced in the germinative zone after the migration of the infragranular neurons and themselves migrate afterwards to the upper cortex between E16 and the first postnatal days. These astrocytes do not display an intermediate stage of the radial glial cell and do not participate in the pattern of appearance of the deeper astrocytes. This second step of astrocytogenesis is a condition for normal cytoarchitectonic development and the maintenance of the supragranular layers, since the deprivation of the astrocytic equipment of the supragranular layers by an antimitotic drug drastically reduces the number of supragranular neurons.

The cytological features, origin, migration, and fate of the subpial granular layer cells of the human embryonic cerebral cortex are studied with light and electron microscopy, Golgi impregnations, and immunocytochemical staining with the microtubule associated protein 2 and glial fibrillary acidic protein antibodies. Subpial granular layer (SGL) cells form a distinct neuronal population in the molecular layer, characterized by a small dark nucleus with abundant chromatin clumps and prominent nucleoli, and a lightly stained cytoplasm containing few organelles. Somata and processes of SGL cells are intensively stained with microtubule-associated protein 2 antibody but do not express glial fibrillary acidic protein antibody. These cells apparently originate from the olfactory germinative zone. They follow two major strands from the olfactory subventricular zone to the subpial region. Subsequently, they migrate tangentially at the subpial level to all cortical regions, as is observed on Golgi and ultrastructural preparations. They constitute a transient population that penetrates the deep molecular layer and subsequently disappear from it. Several cytological features of these cells suggest an inward migration with growth of a radial process toward the cortical plate and subsequent nuclear translocation. The fate and the role of this new phylogenetic neuronal population has yet to be determined although the abundance of degenerating SGL cells in the deep molecular layer suggests at least partial degeneration.

An 8-month-old boy and a 7-month-old girl presented with an acute, Coombs-positive auto-immune haemolytic anaemia and severe hepatitis. The clinical manifestations were pallor, jaundice and hepatomegaly. The liver histology revealed diffuse giant cell transformation and extensive necrosis with central-portal bridging. Combined immunosuppressive regimen with steroids and azathioprine led to prolonged clinical and biological remission with a respective 2 years and 7 months follow up. The girl, however, after 7 months developed a progressive encephalopathy of unknown aetiology, while liver and haematological disease were still under control. She died subsequently from severe recurrent seizures. We conclude that acute Coombs-positive giant cell hepatitis of infancy can be improved by sustained immunosuppressive therapy.

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SUMMARY Excitotoxic disturbances during brain development were studied in the mouse using intracerebral injections of ibotenate, a glutamatergic agonist of the N‐methyl‐D‐aspartatc (NMDA) complex receptor, to analyse the protective effect of a systemic bolus of MgSO4. a non‐competitive antagonist of the NMDA ionophore‐complex receptor. MgSO4 did not prevent microgyia, induced by ibotenate when injected at PO immediately after the post‐migratory settlement of layer V, but did prevent ulegyrias. porencephalic cysts, and other cortical and cortical subcortical hypoxic‐like lesions arising after completion of the neocortical cyto‐architectonic development at P5. Protection was optimal in 80 per cent of mice at 600mg/kg. with no mortality due to MgSO4: thereafter mortality increased with dosage. The protective effect appears after the developmental acquisition of two properties of the excitotoxic cascade, namely the coupling of the massive calcium influx with NMDA‐receptor overstimulation and the predominance of magnesium‐oblilerable calcium channels. This animal model supports the clinical intervention studies with magnesium in hypoxias/perfusion failures and has implications for their design. If maturation of the excitotoxic cascade follows the same sequence in humans, protection is probably low before 26 weeks of gestational age. RÉSUMÉ Prévéntion de la mart ncuronali excitotoxique par le magnésium dans le cerveau en développement Lees lesions excilotoxiques ont étéétudiées duranl le développement cérébral de la souris à lcar;aide dcar;injections intracerebrales dcar;iboténate, un agoniste glutaminergique des récepieurs ionotropiques de type N‐méthyl‐D‐aspartate (NMDA). pour évaluer lcar;effet protecteur dcar;une dose de sulfate de magnésium, un antagoniste non competitif du rccepteur NMDA. CheZ, la souris, le sulfate de magnésium n'empěche pas la survenue de microgyrie induite par lcar;ibotenate quant il est injectéà la naissance. immediatement aprés la mise en place ct la maturation des neurones des couches corticales V et Via. Par eontre. le magnésium empéche les ulégyries, les kystes porencéphaliques et les autres lésions corticales et sous‐corticales de type hypoxique. induils par lcar;injeclion dcar;ibotenate au cinquième jour postnatal aprés la fin du développement cyto‐architectonique néocortical. La protection était optimale chez 80 pour cent des animaux à 600 mg/kg de sulfate de magnésium, sans mortalité secondaire; la mortalité augmente ensuite avec les doses. lcar;effet protecteur apparait aprés lcar;acquisition de deux propriélés de la cascade excitotoxique. le couplage de lcar;linflux calcique massif avec line stimulation excessive des récepteura el lcar;acquisition dcar;une sensibililé du récepteur NMDA à lcar;effet du magnésium. Ce modéle animal justilie les éludes cliniques multicentriques utihsant le magnésium dans les hypoxies/ischémiques du nouveau‐né a terme. Si la maturation de la cascade excitotoxique est similairc dans lcar;espéce humaine, lcar;effet protecteur du magnesium est probablement...