Mitsuyoshi Iwasaki

Supranormal levels of serotonin and its metabolite after raphe cell transplantation in serotonin-denervated rat hippocampus ☆

Transplantation of fetal raphe cells (14 days of gestation) into the adult rat hippocampus, 2 weeks following serotonin (5-HT)-denervation with intracisternal injection of 5,7-dihydroxytryptamine, can restore 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels in the hippocampus to far beyond normal values. Transplantation into the unilateral hippocampus produces asymmetrical turning behavior after administration of the 5-HT releasor, p-chloroamphetamine (IP), comparable to the behavior reported for rats with 5-HT denervation of the unilateral hippocampus. The effect is blocked by prior depletion of 5-HT with p-chlorophenylalanine (IP). The asymmetry in 5-HT levels are correlated with the behavioral change. These data indicate that a large amount of 5-HT is released from nerve terminals of transplanted raphe cells, and suggest that the supranormal levels of 5-HT and 5-HIAA after raphe cell transplantation are neurochemical correlates of 5-HT hyper-innervation of the hippocampus which has been reported previously.

Effects of Interstitial Edema on Brain Cell Transplantation

Fetal raphe cells were transplanted into the anterior part of the corpus callosum of serotonin denervated hydrocephalic rats using a cell suspension method. Hydrocephalus was induced by intracisternal injection of kaolin. The survival of the transplanted cells and fiber outgrowth were evaluated according to the level of serotonin and its metabolite, hydroxyindoleacetic acid, using high-performance liquid chromatography with electrochemical detection in the anterior and posterior parts of the corpus callosum 1-2, 5-6, and 7-8 weeks after transplantation. The results suggest favorable effects of interstitial edema associated with hydrocephalus on the survival of transplanted raphe cells and fiber outgrowth.

Facilitated growth of transplanted raphe cells in hydrocephalic interstitial edema

Fetal raphe cells were transplanted into the anterior corpus callosum (CC) of serotonin (5-HT)-denervated hydrocephalic rats. The levels of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were measured in the anterior and posterior parts of the CC at 1-2, 5-6, and 7-8 weeks posttransplantation. The 5-HT and 5-HIAA levels in the anterior part were restored to their maximum within 5-6 weeks posttransplantation in both hydrocephalic and nonhydrocephalic rats. In contrast, the 5-HT and 5-HIAA levels in the posterior part continued to increase for the period beyond 5-6 weeks posttransplantation. The longer time course of the restoration in the posterior part may reflect the time for fiber growth from the site of transplantation to remote brain areas. Hydrocephalic rats showed slightly higher levels of 5-HT (154.4%) and 5-HIAA (159.5%) in the anterior part, and markedly higher levels of 5-HT (254.8%) and 5-HIAA (388.7%) in the posterior part at 5-6 weeks posttransplantation, compared with nonhydrocephalic rats. These results imply favorable effects of interstitial edema associated with hydrocephalus on the survival of transplanted raphe cells and fiber outgrowth.

Magnetic Resonance Imagings of Alobar and Semilobar Holopresencephaly

We have experienced two patients with holoprosencephaly. These patients had no facial abnormalities except hypotelorism. The prosencephalon is one of the three primitive vesicles which proceeds to cleave sagittaily into the cerebral hemisphere and transversally into the telencephalon and diencephalon (cleavage). In holoprosencephaly such diverticulation or cleavage is disturbed and various patterns of the embryonic holoprosencephalon are retained. Up to this time, computed tomography (CT) was the first diagnostic procedure for these abnormalities. It is, however, insufficient for further evaluation and particularly for the differential diagnosis of diencephalic cyst, absence of the corpus callosum and hydran-encephaly. Compared with CT, magnetic resonance imaging (MRI) was very useful to detect these patient’s abnormalities. The lack of ionizing radiation and other biologic hazards, coupled with its high level of tissue contrast, makes MRI suited for pediatric neuroradiology. Therefore, MRI is an excellent imaging method and could be used as the primary imaging modality for the evaluation of congenital malformations. (Shoni no Noshinkei 12: 67–72, 1987)