Rutgers 提供一种新的方法能够潜在治疗中枢神经系统损伤。据Rutgers的Bonnie Firestein博士称，尿酸普遍认为同极度痛苦的关节疾病—痛风相关，但它同样在脊髓损伤和其它中枢神经系统紊乱治疗中起重要作用，如中风、多发性硬化症和帕金森病。美国新泽西州立大学Rutgers的细胞生物学和神经学助教授Firestein，和她的研究团队在《神经胶质》杂志在线版本上报道了上述研究结果。
背景：
星形胶质细胞是一种特殊细胞，它能够通过释放营养素和缓冲保护作用支持神经元的功能。谷氨酸是正常环境下脑内的一种成分，能够帮助神经元传递脑内的认知功能信号，如学习和记忆。脊髓损伤或中风情况下会出现细胞的损伤，而且出现谷氨酸的过多释放并积聚在未损伤神经元周围，最终导致完整神经元的死亡。
研究结果和结论：
Firestein研究小组将尿酸添加到大鼠脊髓神经元和星形胶质神经细胞混合培养基中，谷氨酸转运蛋白EAAT-1生成显著增加。该研究发现利用药物治疗或其它方法可以最有效的增加转运蛋白的生成。“脊髓损伤，还有中风是两种不同的损伤，” Firestein解释道，“首先出现身体创伤，随后创伤反应释放的化学物质继发刺激出现神经元（神经细胞）的化学损伤。我们发现尿酸可以在创伤的早期阶段作用于星形胶质细胞对化学损伤进行干预。” 尿酸对神经元的健康作用同样由其它研究人员观察到，但它参与保护作用的机制仍是个谜团。“很有趣的现象为痛风的患者不发生多发性硬化症，” Firestein说道。“多发性硬化症的动物模型中，补充尿酸能够减少症状并促进预后。同样在帕金森病的测试中也得到相同的结论。”
后续：
除了科学上的成功，该研究同样可以作为学生参与和教育的模型。联合作者博士后伙伴Yangzhou Du传授大量星形胶质细胞的信息给Firestein，而且他也从Firestein学到了很多神经元的知识。Christopher Chen是参与该实验的Henry Rutgers Honors的本科生，Yuval Eisenberg是一名实验技术员；他们两个都还在医学院中就读。另一名学生Chia-Yi Tseng正在Firestein的实验室进行硕士课题研究。
Firestein研究小组的突破性研究揭示，尿酸能够刺激星形胶质细胞生成转运蛋白将危险化学损伤中神经元的有害成分移除。这为验证新治疗方法作用的独特药物靶点奠定了基础。
Firestein说，Baylor医学院和罗彻斯特大学医学中心的联合研究小组一起参与了该策略的设计。和该联合研究小组一起，Firestein将进一步研究一种改良干细胞系能够分化为星形胶质细胞并产生大量的EAAT-1转运蛋白。将改良的干细胞补充到受伤位点，单独或联合尿酸治疗具有更好的治疗前景。
Uric acid and spinal cord injury treatment
A novel approach from Rutgers holds potential for central nervous system damage
NEW BRUNSWICK/PISCATAWAY, N.J. -- Uric acid is commonly associated with the excruciatingly painful joint disease known as gout, but it can also play a crucial role in the treatment of spinal cord injury and other central nervous system disorders, such as stroke, multiple sclerosis and Parkinson's disease, according to Rutgers' Bonnie Firestein.
Firestein, an associate professor of cell biology and neuroscience at Rutgers, The State University of New Jersey, and her laboratory team have reported their discovery in the Early View (online in advance of print) version of the journal Glia.
"In spinal cord injury, as well as stroke, two kinds of damage can occur," Firestein explained. "First there is the physical damage, but this is followed by secondary chemical damage to neurons [nerve cells] by compounds released in response to the trauma. We have found that uric acid can promote an early intervention step in combating this chemical damage through its action on astroglial cells."
Astroglial cells or astrocytes are specialized cells that support neuron function with nutrients and protective buffering.
In addition to the scientific achievement, the research study is a model for student involvement and education. Among the co-authors, postdoctoral associate Yangzhou Du is teaching Firestein more about astroglial cells, while he is learning about neurons from her. Christopher Chen was a Henry Rutgers Honors undergraduate student on the study, and Yuval Eisenberg, a laboratory technician; both now attend medical school. Another student, Chia-Yi Tseng is continuing her graduate studies in Firestein's laboratory.
Uric acid's effects on the health of neurons had been observed by other researchers, but the mechanics of how it confers protection has remained a mystery.
"It is interesting to note that people with gout never seem to develop multiple sclerosis," Firestein said. "In animal models of multiple sclerosis, the addition of uric acid reduces symptoms and improves prognosis. The same is true for one type of Parkinson's disease tested."
The Firestein team's breakthrough studies revealed that uric acid can stimulate astroglial cells to produce transporter proteins that carry harmful compounds away from neurons in jeopardy of chemical damage. This opens the door to identifying a unique drug target for new therapies.
Glutamate is a compound that under normal circumstances aids neurons in transmitting signals for cognitive functions in the brain, such as learning and memory. In the case of spinal cord injury or stroke where there is physical cell damage, however, an excess of glutamate is released and it accumulates around the remaining intact neurons, eventually choking them to death.
When Firestein's group added uric acid to a mixed culture of rat spinal cord neurons and astroglial cells, the production of the glutamate transporter EAAT-1 increased markedly. The challenge now is find the most effective strategy for increasing the production of the transporter, using drug therapies or other means.
Firestein said that a collaborative team of colleagues from Baylor College of Medicine and the University of Rochester Medical Center has devised one such strategy. With this team, Firestein will develop a line of stem cells that has been modified to generate astrocytes that produce large quantities of the EAAT-1 transporter. Adding these to an injury site, either alone or in combination with uric acid, holds great potential, she said.
http://www.eurekalert.org/pub_releases/2007-01/rtsu-uaa010307.php
编辑：ache
