Analysis of channel transporter after brain injury and its application for treatment

脑损伤后通道转运蛋白的分析及其在治疗中的应用

• 批准号: 13470296
• 负责人: YAMADA Kazuo
• 金额: $ 9.15万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470296/
• 关键词: aquaporin; myoinositol transporter; cerebral ischemia; subarachnoid hemorrhage; cultured astrocyte; neuron; striatal hemorrhage; osmolyte transporter; 神経細胞; アストロサイト; チャンネルトランスポータ; 脳損傷; Na; myoinsitoI cotranspoter; オスモライト トランスポータ

To detect changes in channel transporter, we used models of cerebral ischemia, cold-induced edema, subarachnoid hemorrhage (SAH) and intracerebral hemorrhage in rat. The transporters we detected are aquaporin type 1, 4,5 and 8, and myoinositol osmolyte transporter. In the cerebral ischemia, aquaporin type 4 mRNA is expressed in 3 to 7 days after ischemia, and aquaporin type 4 protein is increased in soma and disappearing from vascular foot, indicating turnover of aquaporin 4 is occurring. Similar findings are detected in the cold-induced edema model, indicating that aquaporin type 4 is functioning for resolution of brain edema. On the other hand aquaporins 1,4,5 and 8 is expressed in the cultured astrocyte exposed to hypoxia, indicating multipotential nature of aquaporins. Myoinositol transporter, one of the osmolyte transporters, is expressed in the neurons facing subarachnoid blood of SAH model, indicating osmotic pressure changes in SAH. Myoinositol transporter mRNA is also expressed in the neurons exposed to transient ischemia after SAH, indicating osmolyte changes in cerebral ischemia. We have detected cell death in substantial nigra after striatal hemorrhage in rat. During this process nigral neurons expressed myoinositol mRNA expression, which may relate to cell death. In Summary, channel transporter plays important role in brain injury and its recovery. Treatment trial must be focused in this area.

为了检测通道转运体的变化，我们使用了大鼠脑缺血、冷致水肿、蛛网膜下腔出血(SAH)和脑出血的模型。我们检测到的转运蛋白是水通道蛋白1、4、5和8型，以及肌醇渗透膜转运蛋白。在脑缺血时，水通道蛋白4型在缺血后3~7d有表达，水通道蛋白4型蛋白在胞体表达增加，血管足消失，表明水通道蛋白4正在发生周转。在冷诱导的水肿模型中也发现了类似的发现，表明水通道蛋白4型在解决脑水肿方面发挥着作用。另一方面，低氧条件下培养的星形胶质细胞表达水通道蛋白1、4、5和8，表明水通道蛋白具有多潜能。肌醇转运体是一种渗透压转运体，在蛛网膜下腔出血模型的神经细胞中有表达，提示蛛网膜下腔出血时渗透压的变化。SAH后暴露于短暂性脑缺血的神经元中也有肌醇转运体mRNA的表达，提示脑缺血时渗透压的变化。我们检测到大鼠纹状体出血后黑质实质细胞死亡。在此过程中，黑质神经元表达了肌醇mRNA，这可能与细胞死亡有关。综上所述，通道转运体在脑损伤及其恢复中起着重要作用。治疗试验必须集中在这一领域。

项目成果

Ueda T, Yamada K, Shimada S, et al.: "Diffuse brain injury induces local expression of Na+/myo-inositol cotransporter in the rat brain"Mol Brain Res.. 86. 63-69 (2001)

Ueda T、Yamada K、Shimada S 等：“弥漫性脑损伤诱导大鼠脑中 Na /肌醇协同转运蛋白的局部表达”Mol Brain Res.. 86. 63-69 (2001)

Katano H, Fujita K, Asai K, Masago A, Yamada K: "A metabotropic glutamate receptor antagonist, alpha-methyl-4-carboxyphenyiglycine, attenuates immediate early gene mRNA expression following traumatic injury in cultured rat cortical glial cells"Neurosci Le

Katano H、Fujita K、Asai K、Masago A、Yamada K：“代谢型谷氨酸受体拮抗剂 α-甲基-4-羧基苯甘氨酸，可减弱培养的大鼠皮质胶质细胞创伤性损伤后立即早期基因 mRNA 的表达”Neurosci Le

Mase M, Yamada K, Matsumoto T, Iida A: "PET study in patients with neuropsychological impairments in the chronic state after traumatic diffuse brain injury in Gjedde A, Hansen SB, Kundsen GM, Paulson OB: Physiological Imaging of the Brain with PET"Academi

Mase M、Yamada K、Matsumoto T、Iida A：“Gjedde A、Hansen SB、Kundsen GM、Paulson OB 的创伤性弥漫性脑损伤后慢性状态神经心理损伤患者的 PET 研究：用 PET 对大脑进行生理成像”

Fujita M, Aihara N, Yamada K: "Regulation of rat hippocampal neural cadherin in the kainic acid induced seizures"Neurosci Lett 297:13-16, 2001. 297. 13-16 (2001)

Fujita M、Aihara N、Yamada K：“红藻氨酸诱导的癫痫发作中大鼠海马神经钙粘蛋白的调节”Neurosci Lett 297:13-16, 2001. 297. 13-16 (2001)

Yoneda K, Yamada K, Kato T: "Regulation of aquaporin-4 expression in astrocytes"Mol Brain Res. 89. 94-102 (2001)

Yoneda K、Yamada K、Kato T：“星形胶质细胞中水通道蛋白 4 表达的调节”Mol Brain Res。