Investigation About Molecular Biological Changes In Diffuse Axonal Injury Model And Therapeutic Possibility With Neurotrophic Factors

弥漫性轴突损伤模型的分子生物学变化及神经营养因子治疗可能性的研究

• 批准号: 08671580
• 负责人: KOHMURA Eiji
• 金额: $ 1.41万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671580/
• 关键词: diffuse axonal injury; head injury; neurotrophic factor; molecular biology

An animal model of diffuse axonal injury was first produced. ASD rat was placed on urethane foam with a steel helmet on the exposed skull under general anesthesia. The helmet was hit by a free falling weight of 450g. The height was adjusted to 1.5 meter so that animal survival could be expected. Most animals presented with apnea and convulsion for a short period. Histological examination revealed that axonal retraction balls and swelled axons are produced in the basal pons till 2 weeks. We tried to find changes of mRNA coding receptors for neurotrophic factors but failed to detect them because there were variations of injury severity between animals and the sensitivity of detection method.Next, we tried to find usefulness of minipellet containing BDNF (200mg). This minipellet can release BDNF continuously for about one week. We examined the effect on the model of facial never injury and intracerebral hematoma, because facial motoneurons and dopaminergic neurons of substantia nigra are known to respond against BDNF.Recovery of facial function was accelerated by BDNF minipellet. Tyrosine hydroxylase positive neurons were well preserved in the substantia nigra in the hematoma model by BDNF pellet. To apply trophic factors via minipellet may be clinically feasible. We should further study the precise mechanism of the action of trophic factors.

首次建立了弥漫性轴索损伤的动物模型。在全身麻醉下，将ASD大鼠放置在聚氨酯泡沫上，暴露的头骨上戴着钢盔。头盔被450 g的自由落体重量击中。将高度调整为1.5米，以便预期动物存活。大多数动物出现短暂的呼吸暂停和惊厥。组织学检查显示，至2周时，基底脑桥内出现轴突回缩球和肿胀轴突。我们试图发现编码神经营养因子受体的mRNA的变化，但由于动物之间的损伤严重程度和检测方法的灵敏度存在差异，因此未能检测到它们。该微丸可持续释放BDNF约一周。由于面神经运动神经元和黑质多巴胺能神经元对BDNF有反应，我们在面神经损伤和脑内血肿模型上研究了BDNF微棒对面神经功能恢复的影响。脑源性神经营养因子颗粒血肿模型黑质内酪氨酸羟化酶阳性神经元保存完好。通过微条应用营养因子在临床上是可行的。我们应该进一步研究营养因子作用的确切机制。

项目成果

Kohmura E: "Antisense oligonucleotide for heat shock protein increases loss of CA3 neurons in hippocampal slice." J Cereb Blod Flow Metab. 17. S488- (1997)

Kohmura E：“热休克蛋白的反义寡核苷酸会增加海马切片中 CA3 神经元的损失。”

Kohmura E: "Altered expression of Growth Inhibitory Factor (GIF/MT-III) mRNA in the rat facial nucleus after facial nerve injury is closely related with facial function" Restorative Neurology and Neuroscience. 11. 169-175 (1997)

Kohmura E：“面神经损伤后大鼠面核中生长抑制因子 (GIF/MT-III) mRNA 表达的改变与面部功能密切相关”《恢复神经病学和神经科学》。

Yamashita T: "Changes in glutamate/aspartate transporter (GLAST/GluT-1) mRNA expression following facial nerve transection." Mol Brain Res. 38. 294-299 (1996)

Yamashita T：“面神经横断后谷氨酸/天冬氨酸转运蛋白 (GLAST/GluT-1) mRNA 表达的变化。”

Yamashita T: "Changes in glutamate/aspartate transporter(GLAST/GluT-1)mRNA expression follwing facial nerve transection." Mol Brain Res. 38. 294-299 (1996)

Yamashita T：“面神经横断后谷氨酸/天冬氨酸转运蛋白 (GLAST/GluT-1) mRNA 表达的变化。”

Kohmura E: "Altered expression of Growth Inhibitorv Factor (GIF/MT-III) mRNA in the rat facial nucleus after facial nerve injury is closely related with facial function." Restorative Neurology and Neuroscience. 11. 169-175 (1997)

Kohmura E：“面神经损伤后大鼠面核中生长抑制因子（GIF/MT-III）mRNA表达的改变与面部功能密切相关。”