Neurochemical and histochemical studies on the mechanism and prevention of cerebellar under-development due to perinatal hyperbilirubinemia

围产期高胆红素血症导致小脑发育不良的机制及预防的神经化学和组织化学研究

• 批准号: 62570446
• 负责人: KEINO Hiroomi
• 金额: $ 1.22万
• 依托单位: Institute for Developmental Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570446/
• 关键词: neonatal-jaundice; bilirubin; cerebellar hypoplasia; drugtherapy; hemeoxygenase; tin-protoporphyrin; 動物モデル; ヘムオキシゲナーゼ; 錫プロトポルフィリン; プルキンエ細胞

It is known that the cerebellar hypoplasia of jaundiced homozygous (j/j) Gunn rats is caused by neonatal hyperbilirubinemia. The hypoplasia is more severely exhibited in the antero-medial lobules and even less in the posterior lobules. The histochemical observations showed that Purkinje cells in the antero-medial lobules were more acidic than the posterior, and that a larger quantity of bilirubin was bound to purkinje cells in the former which is sensitive to bilirubin than in the latter which is tolerant to the pigment.Tin-protoporphyrin (SnPP) is a powerful competitive inhibitor of the heme oxygenase and is now tested clinically for jaundiced patient. Intraperitoneal or subcutaneous administration of SnPP to j/j rat neonates caused a rapid decrease of the serum bilirubin level, an apparent reduction of the mortality rate and hence protection against the cerebellar hypoplasia. Unexpectedly, however, the cerebellar underdevelopment of j/j rats was not so markedly improved. The combination of SnPP treatment and photoirradiation induced death with a high mortality; more than half of the infants were dead 4h after treatment by 20

已知黄褐性纯合子(j/j)Gunn大鼠的小脑发育不良是由新生儿高胆红素血症引起的。前内侧小叶发育不良较重，后小叶发育不良较少。组织化学观察表明，前内侧小叶的浦肯野细胞比后内侧小叶的酸性更强，前者对胆红素敏感的浦肯野细胞比后者对胆红素耐受的浦肯野细胞结合更多的胆红素。锡原卟啉(SnPP)是一种强大的血红素加氧酶竞争性抑制剂，目前已用于临床。给J/J新生大鼠腹腔或皮下注射SnPP后，血清胆红素水平迅速下降，死亡率明显降低，从而对小脑发育不良有保护作用。然而，出乎意料的是，J/J大鼠的小脑发育不良并没有得到明显改善。SnPP联合光照组死亡率高，治疗4h后半数以上婴儿死亡。

项目成果

S. Kashiwamata: "Animal models for cerebellar development" Hereditary. 41. 43-48 (1987)

S. Kashiwamata：“小脑发育的动物模型”遗传性。

H.Nagae: Pediatric Research.

H.Nagae：儿科研究。

H.Keino: Neuroscience Research. 6. (1989)

H.Keino：神经科学研究。

H. Keino: "Critical period of bilirubin-induced cerebellar hypoplasia in a new Sprague-Dawley strain of jaundiced Gunn rats" Neuroscience Research. 6. (1989)

H. Keino：“黄疸 Gunn 大鼠新 Sprague-Dawley 品系中胆红素诱导的小脑发育不全的关键期”神经科学研究。

渡辺智正: Medical lmmunology. 15. 759-764 (1987)

渡边友正：医学免疫学。15. 759-764 (1987)