Sadataka Houdou

Development of myelination in the human fetal and infant cerebrum: A myelin basic protein immunohistochemical study

The early development of myelination was studied by means of myelin basic protein (MBP) and luxol fast blue (LFB) stainings of large sections of the cerebral hemispheres. Myelination first occurs in the globus pallidus, pallidothalamic fibers of the posterior internal capsule and the thalamus at 25 weeks, which may be related to the cellular maturation in the globus pallidus and thalamus. Then myelination is observed in the striatum, and precentral and postcentral gyri at 35 weeks, and the anterior internal capsule and optic radiation at 37 weeks. Immunoreactivity with MBP is observed earlier and more strongly in the early myelination period than that with LFB. Thus, MBP may play an important role in myelination and its delay. The macroscopic positivity as to MBP as well as LFB staining may be related to the development of high signal intensity observed in a T1-weighted magnetic resonance imaging, which was observed 1 to 3 months after the first microscopic appearance of myelin.

Developmental immunohistochemistry of catalase in the human brain

The immunohistochemical studies on a peroxisomal enzyme, catalase, were done on brains from human fetuses to adults. The catalase-positive neurons appeared in the basal ganglia, thalamus and cerebellum at 27-28 weeks of gestation, and in the frontal cortex at 35 weeks. They then increased in number with gestational age. The extent of immunopositive staining increased with enlargement of perikaryonal size. However, the extent gradually decreased with postnatal age. On the other hand, catalase-positive glia appeared in the deep white matter at 31-32 weeks of gestation, their appearance shifting from the deep to the superficial white matter with increasing age. These results suggest that peroxisomes are closely related to neuronal growth and myelinogenesis in the human brain during development.

Varicella with Delayed Hemiplegia

We report 4 children who developed acute hemiplegia 7 weeks to 4 months after varicella infection. In 2 patients, carotid angiography demonstrated segmental narrowing and occlusion of the middle cerebral artery. Their clinical and angiographic features were similar to those associated with contralateral hemiplegia after herpes zoster ophthalmicus, the pathogenesis of which comprises cerebral angiitis due to varicella zoster viral infection. We believe that our patients had the same pathogenesis. In a survey of infectious diseases in our region, the frequency of varicella with delayed hemiparesis was roughly 1:6,500 varicella patients.

Relationship between periventricular hemorrhage, leukomalacia and brainstem lesions in prematurely born infants.

The brain pathology in very prematurely born infants with intraventricular hemorrhage (IVH) was studied particularly as to the severity and site of the complicated brain lesions responsible for the prognosis. A high frequency of leukomalacia, pontosubicular necrosis and/or olivocerebellar neuronal loss was found in the cases of IVH, and these non-hemorrhagic brain lesions showed an increasing frequency with the grade of IVH. However, there was marked reduction of IVH, periventricular leukomalacia and, in particular, brainstem lesions in prematurely born cases of sudden infant death. These IVH and associated conditions have different pathogenesis, but factors responsible for their occurrence may be present together in each case.

Immunohistochemical Expression of Peroxisomal Enzymes in Developing Human Brain

The immunohistochemistry of peroxisomes was examined in human brains from fetal to adult ages using antibodies against catalase (CAT), acyl-CoA oxidase (AOX), and 3-ketoacyl-CoA thiolase (PT) on conventional formalin-fixed paraffin-embedded sections. Positive staining neurons first appeared in the basal ganglia, thalamus, and cerebellum at 27-28 wk of gestation, and in the frontal cortex at 35-36 wk of gestation. They increased in number with gestational age and the intensity of immunostaining increased with enlargement of perikaryonal size. Positively staining glial cells first appeared in the deep white matter at 31-32 wk of gestation, their appearance showing a shift from the deep to the superficial white matter with increasing age. This developmental change in the peroxisomal immunoreactivities in glial cells corresponds with that in myelination glia. Therefore, the results suggest that peroxisomes are closely related to neuronal growth and myelinogenesis in the developing human brain. Also, our results as to myelinogenesis may explain one pathogenetic factor of dysmyelination in peroxisomal disorders.

Immunohistochemical study of the vasculature in the developing brain

In this study, the developmental proliferation of human brain vessels, from the fetal to the adult stage, was analyzed by immunohistochemical methods using antitype IV collagen, antilaminin, and antifibronectin antibodies. Examination of the frontal lobe indicates that these antibodies bind to the vessels, both arteries and veins. During cortical angiogenesis, the density and diameter of vessels increase rapidly from about 26 weeks gestation and peak at 35 weeks; after 35 weeks, the density and diameter of vessels are the same as those in adult brain. The white matter demonstrates no major changes in vessel density, although the pattern of the changes in vessel diameter resembles that of the cortex. Small immunopositive spots suggesting neovascularization reveal the same developmental tendency as the density of vessels in the cortex and white matter; therefore, it appears that neovascularization in the fetal brain during development is more rapid than cortical expansion and is equal to the growth of white matter. Neovascularization may be closely related to normal brain development and may play an undefined role in perinatal cerebrovascular insults.

Developmental change in type VI collagen in human cerebral vessels

Vascular development in the human brain was studied by immunohistochemistry using an anti-type VI collagen antibody. Positive vessels were evident from an early gestational age in the meninges, from 21 weeks gestation in the basal ganglia and deep white matter, and from 38 weeks gestation in the cerebral cortex and superficial white matter; however, type VI collagen never appeared in the subependymal germinal layer. The absent or scarce type VI collagen in the subependymal germinal layer may be one of the important factors of subependymal/intraventricular/periventricular hemorrhage in premature neonates. The earlier appearance of positive vessels in the deep white matter than in the cortex and superficial white matter suggests that the medullary vein develops earlier than the cortical and subcortical veins and arteries. These characteristics of the developing vascular structure may be one cause of perinatal brain damage.

Joubert syndrome associated with unilateral ptosis and leber congenital amaurosis

Two siblings are described with clinical features of Joubert syndrome associated with unilateral ptosis, severe visual disturbances with normal appearing fundi, and an occipital meningocele; one child also had polydactyly. Neither child manifested responses to electroretinography and one did not manifest visual evoked potentials. The siblings were considered to have characteristics of Leber congenital amaurosis and Joubert syndrome as well as unilateral ptosis. The presence of these findings in siblings suggests a genetic basis for their disease. Careful investigations should be conducted on infants with dysplasia of the cerebellar vermis, including tests for respiratory irregularities, retinal abnormalities, and renal abnormalities to further clarify the interrelationships of these conditions.

Immunohistochemistry of superoxide dismutase-1 in developing human brain

The developmental changes in superoxide dismutase (SOD)-1 were studied in brains ranging in age from human fetuses to adults by immunohistochemistry. SOD-positive neurons and glial cells appeared with maturation in each region, and increased progressively with gestational and postnatal age. This phenomenon implies a relationship between SOD-1 gene expression and the anti-oxidant defence mechanism in developing neurons and glia.

Clinicopathologic studies on leptomeningeal glioneuronal heterotopia in congenital anomalies

Leptomeningeal glioneuronal heterotopia was observed in 40 of 129 autopsied infants (31%). It was present in 49% of patients who had congenital anomalies in general and in 65% of patients who had central nervous system malformations. Most of the leptomeningeal glioneuronal heterotopias appeared in the base of the brain (62.5%), midbrain (40%), frontal lobe (37%), and pons (35%). Leptomeningeal glioneuronal heterotopia is closely related to migration disorders on the basis of frequent association with polymicrogyria or neuronal heterotopias.