成年哺乳动物脊髓损伤神经的鲁棒再生

2010年8月8日

波士顿，大众。-研究者首次在受伤的成年脊髓网站上诱导了神经组织的连接，控制了自主运动。这些研究结果提供了希望，它可能是可能的设计治疗瘫痪和其他功能障碍的脊髓损伤所产生的运动功能。

在啮齿类动物的研究中，波士顿儿童医院，UC Irvine，UC San迭戈队取得这一突破回头的分子通道的发育时钟在皮质脊髓束神经生长的关键。皮质脊髓束是一束神经连接大脑和脊髓。尽管一定程度的神经再生已在成熟的中枢神经系统（CNS），其他地区实现成人皮质脊髓神经都特别耐损伤后的再生。

皮质脊髓神经再生是通过删除PTEN的实现，一种酶作为细胞生长的一个关键的制动。一个重要的生长的分子，其活性可以控制由PTEN是mTOR。在生命的早期阶段，PTEN活性低，使mTOR促进发育生长过程。在以后的阶段，增加PTEN活性和mTOR的活性降低，生长受到更多的限制。

在受伤的中枢神经系统中如何恢复早期发育期细胞的生长，志刚, a neurology associate professor at 波士顿儿童医院 -working with穆斯塔法沙欣，也是儿童神经内科-显示在2008项研究中，调节PTEN、mTOR通路启用从眼睛再生新连接到大脑的视神经损伤后。他现在与奥斯瓦尔德斯图尔特从UCI和滨海郑UCSD使用相同的方法来诱导脊髓损伤部位的神经再生。

他们的研究结果出现在8月8日的在线版自然神经科学。

Nerve regeneration in mouse spinal cord。 Deletion of the enzyme PTEN allows corticospinal nerves - which control voluntary movement - to regenerate past a lesion site。

"Until now, such nerve regeneration has been impossible in the spinal cord," says Oswald Steward, anatomy & neurobiology professor and director of the Reeve-Irvine Research Center at UCI。 "Paralysis and loss of function from spinal cord injury has been considered untreatable, but our discovery points the way toward a pathway to develop a therapy to induce regeneration of nerve connections following spinal cord injury in people。"

In addition to extending optic nerve findings to the spinal cord, He points out that the current study makes the advance of showing that the regenerating nerves actually make anatomical connections with other nerve cells beyond the lesion site。

"We demonstrate that the regenerating nerves can form synapses in the spinal cord," he says。 Synapses are the points of contact between nerve cells, crucial for transmitting signals。 Synapses in the spinal cord allow nerve impulses from the brain to be conveyed to the limbs and other regions of the body。

Spinal cord injuries are due primarily to the interruption of connections between the brain and spinal cord。 An injury the size of a grape can lead to a complete loss of function below the level of the injury。 For example, an injury to the neck can cause complete paralysis of arms and legs, loss of ability to feel below the shoulders, loss of ability to control the bladder and bowel, loss of sexual function and secondary health risks including susceptibility to urinary tract infections, pressure sores and blood clots due to inability to move the legs。

Approximately 2 percent of American has some form of paralysis as a result of spinal cord injury, according to Christopher & Dana Reeve Foundation data。

"These devastating consequences occur even though the spinal cord below the level of the injury is intact," Steward says。 "All these lost functions could be restored if we could find a way to regenerate the connections that were damaged。"

He, Steward and their colleagues are now asking whether the PTEN-deletion treatment leads to restoration of motor function in mice with spinal cord injury。 While the finding of anatomical connections between regenerating nerves and nerve cells beyond the lesion site is encouraging, in order for nerve regeneration to result in restoration of motor function the anatomical connections must represent real sites of information transfer。

"We are closely collaborating with Os's lab in studying functional recovery after spinal cord injury," says He。

Much further study is also needed to translate these findings into therapeutic strategies because PTEN is a tumor suppressor and is known to control numerous important cellular functions beyond nerve regeneration, He explains。 A PTEN-targeted therapy would have to be delivered transiently and in a location-specific manner。 Future studies may explore the efficacy of combining therapeutic approaches that target growth inhibitory molecules within nerve cells, like PTEN, with approaches that target the external growth inhibitory molecules found at CNS lesion sites。

接触：
克里斯特德曼
617-919-3110
keri。stedman@childrens。harvard。edu

波士顿儿童医院 is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869。 More than 1,100 scientists, including nine members of the National Academy of Sciences, 12 members of the Institute of Medicine and 13 members of the Howard Hughes Medical Institute comprise Children's research community。 Founded as a 20-bed hospital for children, 波士顿儿童医院 today is a 396-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families。 Children's also is the primary pediatric teaching affiliate of Harvard Medical School。 For more information about the hospital and its research visit:www。childrenshospital。org/newsroom。

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