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【medical-news】【资讯翻译】研究发现在大脑受损区域植入新的神经细胞有望修复大脑功能

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http://www.news-medical.net/news/20111125/Transplantation-of-new-neurons-into-damaged-area-of-the-brain-could-restore-brain-functions.aspx

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Without neurons reacting to the blood leptin level, the brain does not control the feeling of hunger and fullness. This type of genetic defects results in severe obesity in humans and animals. Scientists from Harvard University (HU), Massachusetts General Hospital (MGH) and the Nencki Institute of Experimental Biology of the Polish Academy of Sciences (Nencki Institute) in Warsaw have demonstrated in their experiments on mice that it is possible to restore brain functions by transplantation of small numbers of new neurons into the damaged area of the brain.

"A spectacular effect in the brain repair that we were able to achieve was significantly reduced weight of genetically defective obese mice and further significant reduction of adverse symptoms accompanying diabetes", says Dr. Artur Czupryn (Nencki Institute, HU, MGH), first author of a paper published in the latest issue of "Science".

Already for some time medicine has attempted to repair damaged brain fragments through transplants of stem cells. These interventions are risky. Transplanted cells often develop in an uncontrolled manner, which frequently leads to cancer.

The aim of the research carried out for the past five years at HU, MGH and the Nencki Institute was to show that transplantation of small numbers of cells could restore the missing neuronal circuits and restore the lost brain functions. Genetically defective mice, deficient in leptin receptor, have been used in these experiments. Leptin is a protein secreted from cells of the fat tissue into the blood when eating. When it reaches the hypothalamus, it reacts with specific neurons and its presence or its low level cause the feeling of fullness or hunger, respectively. Leptin receptor deficient mice do not know the feeling of fullness. They weigh up to twice more than healthy individuals and suffer from advanced diabetes.

The team from Harvard University and Nencki Institute focused on the transplants of immature neurons (neuroblasts) and progenitors, which are specific stem cells with already determined developmental direction. Cells isolated from small regions of developing embryonic brains of healthy mice were used for transplantations. Thus, the probability increased that cells introduced into recipients' brains will transform into neurons or accompanying glial cells.

Millions of cells are usually transplanted. In this project, however, scientists injected a suspension of barely several thousand progenitors and neuroblasts into the hypothalamus of mice. About 300 nanolitres of cell suspension was injected into the mouse hypothalamus in the course of low invasive method - by a thin micropipette with a diameter only several times larger than individual cells.

"The suspension was introduced into strictly defined region of the hypothalamus of mice, measuring about 200-400 micrometres in length. We were able to locate it thanks to unique high-frequency ultrasound microscopic guidance available at Harvard University. It allowed us to carry out complex non-invasive microtransplants with unprecedented precision, because we were able to carry out high resolution imaging of both the brain structures as well as the introduced micropipette", says Dr. Czupryn.

All transplanted cells have been marked with a fluorescent protein, which made possible to follow them in the recipients' brains. Observations carried out 20 or more weeks after the procedure have shown that almost half of transplanted cells transformed into neurons with typical morphology, producing proteins characteristic for normal neurons. By applying sophisticated research techniques, it was possible to demonstrate that the entire range of missing types of neurons was restored in the brain centre for controlling hunger and fullness. Moreover, the new neurons have already formed synapses and communicated with other neurons in the brain, as well as reacted properly to changes in levels of leptin, glucose, and insulin.

The final proof for restoration of proper functioning of the hypothalamus in mice was brought by measurements of body weight and blood metabolic factors. Unlike control population of genetically defective obese mice, the weight of mice with transplanted neurons resembled normal weight. Reversal of unfavourable changes of the blood metabolic parameters has also been observed.

"Many attempts have been described in the literature to date of transplanting cells into the brain. We have shown that a really small transplant of neuroblasts and progenitors was able to reconstitute damaged brain areas and influence the whole organism. We have shown that it is possible to introduce new neurons, which function properly, integrate well into the recipient nervous tissue and restore missing brain functions. Moreover this method turned out to be low invasive and safe, since it did not lead to tumour formation", sums up Dr. Czupryn.

Results achieved by the group from Harvard University and the Nencki Institute define a promising research direction, which could lead to the development of new repair therapies. This novel method could help, for example, eliminate the effects of stroke or improve the treatment of Parkinson's disease, which is associated with dysfunction within a defined brain area. Scientists emphasize however that long years of experiments, research, and tests are needed before therapies based on their ideas end up in the clinics and hospitals.

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2011-11-26 09:19 浏览 : 693 回复 : 5

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2011-11-26 13:07

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• 【原创】呼衰和心衰患者转入ICU，治疗已经没有意义时，你是医生会怎么做？

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1、Without neurons reacting to the blood leptin level, the brain does not control the feeling of hunger and fullness. This type of genetic defects results in severe obesity in humans and animals. Scientists from Harvard University (HU), Massachusetts General Hospital (MGH) and the Nencki Institute of Experimental Biology of the Polish Academy of Sciences (Nencki Institute) in Warsaw have demonstrated in their experiments on mice that it is possible to restore brain functions by transplantation of small numbers of new neurons into the damaged area of the brain.

对血液中的廋素水平变化，神经元丧失反应将导致大脑不能控制饥饿与饱胀感。这种类型的遗传缺陷造成人类、动物的严重肥胖。来自哈佛大学(HU)、马萨诸塞州总医院(MGH)、波兰科学院实验生物学Nencki研究所(Nencki Institute)的科学家们在华沙宣布在他们的小鼠实验中，有可能通过移植小数量的新生神经元到受损区域来重建脑功能。

2、"A spectacular effect in the brain repair that we were able to achieve was significantly reduced weight of genetically defective obese mice and further significant reduction of adverse symptoms accompanying diabetes", says Dr. Artur Czupryn (Nencki Institute, HU, MGH), first author of a paper published in the latest issue of "Science".
Artur Czupryn医生（第一作者身份在Science杂志发表一篇论文）说“我们能获得的一个惊人的脑修复效果是显著降低遗传缺陷肥胖鼠的体重，而且进一步降低糖尿病的严重并发症。”

3、Already for some time medicine has attempted to repair damaged brain fragments through transplants of stem cells. These interventions are risky. Transplanted cells often develop in an uncontrolled manner, which frequently leads to cancer.
医学界已经长时间尝试通过移植干细胞修补局部损伤的脑组织。但这种措施是危险的，因为移植的干细胞经常是无序生长，而这种生长方式通常能导致癌症发生。

4、The aim of the research carried out for the past five years at HU, MGH and the Nencki Institute was to show that transplantation of small numbers of cells could restore the missing neuronal circuits and restore the lost brain functions. Genetically defective mice, deficient in leptin receptor, have been used in these experiments. Leptin is a protein secreted from cells of the fat tissue into the blood when eating. When it reaches the hypothalamus, it reacts with specific neurons and its presence or its low level cause the feeling of fullness or hunger, respectively. Leptin receptor deficient mice do not know the feeling of fullness. They weigh up to twice more than healthy individuals and suffer from advanced diabetes.

在哈佛大学(HU)、马萨诸塞州总医院(MGH)、波兰科学院实验生物学Nencki研究所(Nencki Institute)，这项科研已经进行了5年。它的目的是证实移植小数量的细胞能重建缺损的神经元回路、修复丧失的脑功能。缺乏廋素受体的遗传障碍鼠已经被用于这些实验。廋素是进食时，脂肪组织分泌到血液中的一种蛋白。当它到达下丘脑，将特异性与神经元发生反应。它的存在与否或者水平低下可分别导致饱胀或饥饿感。廋素受体缺乏的小鼠不知道饱胀感。它们的体重是健康小鼠的两倍且出现严重糖尿病。

5、The team from Harvard University and Nencki Institute focused on the transplants of immature neurons (neuroblasts) and progenitors, which are specific stem cells with already determined developmental direction. Cells isolated from small regions of developing embryonic brains of healthy mice were used for transplantations. Thus, the probability increased that cells introduced into recipients' brains will transform into neurons or accompanying glial cells.
来自哈佛大学和Nencki协会的研究团队的科研目标集中在未成熟神经元（神经母细胞）和祖神经元的移植。这两类细胞是特异的神经干细胞且已经确定了分化发生的方向。它们是从正在发育、健康鼠的胚胎大脑的小块组织中分离、获得并用于移植。因此当导入受体的脑中，这些细胞转变为神经元或伴行的胶质细胞的可能性增加。
6、Millions of cells are usually transplanted. In this project, however, scientists injected a suspension of barely several thousand progenitors and neuroblasts into the hypothalamus of mice. About 300 nanolitres of cell suspension was injected into the mouse hypothalamus in the course of low invasive method - by a thin micropipette with a diameter only several times larger than individual cells.
通常情况下，被移植的细胞打数百万。但是在这科研项目中，科学家注入仅仅数千个神经元前体和神经母细胞的混悬液到鼠的下丘脑。以低侵袭性的方法（用一纤细的微量加液器其直径仅数倍于单细胞），
约300纳升细胞悬液被注入鼠下丘脑，

7、"The suspension was introduced into strictly defined region of the hypothalamus of mice, measuring about 200-400 micrometres in length. We were able to locate it thanks to unique high-frequency ultrasound microscopic guidance available at Harvard University. It allowed us to carry out complex non-invasive microtransplants with unprecedented precision, because we were able to carry out high resolution imaging of both the brain structures as well as the introduced micropipette", says Dr. Czupryn.
Czupryn医生说：“这混悬液被导入严格定义的鼠的下丘脑区域，该区域测量长度约200－400微米。我们能够定位精确是因为操作是在一独特的高分辨率的超声显微镜下引导（该设备在哈佛大学）。它能让我们进行复杂的无侵袭的显微植入且无以伦比的精确，就是因为我们能对脑部结构以及所导入的微量加液器进行高分辨率的影像扫描。

8、All transplanted cells have been marked with a fluorescent protein, which made possible to follow them in the recipients' brains. Observations carried out 20 or more weeks after the procedure have shown that almost half of transplanted cells transformed into neurons with typical morphology, producing proteins characteristic for normal neurons. By applying sophisticated research techniques, it was possible to demonstrate that the entire range of missing types of neurons was restored in the brain centre for controlling hunger and fullness. Moreover, the new neurons have already formed synapses and communicated with other neurons in the brain, as well as reacted properly to changes in levels of leptin, glucose, and insulin.
所有移植细胞均已标记上荧光蛋白，这使跟踪它们成为可能。操作完成后20多周，观察显示几乎一半的移植细胞转变为具有典型形态的神经元，产生了正常神经元特征性蛋白。通过应用尖端研究技术，或许能显示在大脑中心区域且功能为控制饥饿和饱胀的脑组织内部，缺损的多类型神经元被修复的全过程。而且新的神经元已经形成突触，并与脑部其他神经元发生联系，以及能对廋素、血糖、胰岛素水平改变产生正常的反应。

9、The final proof for restoration of proper functioning of the hypothalamus in mice was brought by measurements of body weight and blood metabolic factors. Unlike control population of genetically defective obese mice, the weight of mice with transplanted neurons resembled normal weight. Reversal of unfavourable changes of the blood metabolic parameters has also been observed.
重建了鼠下丘脑的正常功能的最终的证据是通过测量体重和血液代谢指标获得的。与遗传缺陷障碍鼠这一对照群体不同，移植神经元的鼠体重类似正常鼠体重，且逆转异常改变的血代谢性指标也能被观察。

10、"Many attempts have been described in the literature to date of transplanting cells into the brain. We have shown that a really small transplant of neuroblasts and progenitors was able to reconstitute damaged brain areas and influence the whole organism. We have shown that it is possible to introduce new neurons, which function properly, integrate well into the recipient nervous tissue and restore missing brain functions. Moreover this method turned out to be low invasive and safe, since it did not lead to tumour formation", sums up Dr. Czupryn.
Czupryn总结到：“至今，对于移植细胞到大脑，许多尝试已经被描述在文献中。我们的结果已经显示移植非常少的神经母细胞和神经元祖细胞能重建毁坏的脑组织区域和影响整个机体组织。我们的结果显示可能植入新的、功能正常的神经元，它就能很好地与周围神经组织结合并重建缺失的脑功能。而且这种方法显示是低侵袭性和安全，因为它不导致肿瘤形成。”
11、Results achieved by the group from Harvard University and the Nencki Institute define a promising research direction, which could lead to the development of new repair therapies. This novel method could help, for example, eliminate the effects of stroke or improve the treatment of Parkinson's disease, which is associated with dysfunction within a defined brain area. Scientists emphasize however that long years of experiments, research, and tests are needed before therapies based on their ideas end up in the clinics and hospitals.

哈佛大学和Nencki研究所的研究团队所获得成果明确了一个有希望的研究方向，能导致新的修复方法的产生。这项新方法有助于，如减少卒中后遗症或者提高帕金森（一种明确脑区域的功能障碍疾病）的治疗水平。但是科学家强调：基于他们的思路所产生的治疗手段在应用在临床、医院前，还需要数年实验、研究和监测。

2011-11-27 00:15

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对血液中的廋素水平变化，神经元丧失反应将导致大脑不能控制饥饿与饱胀感。这种类型的遗传缺陷造成人类、动物的严重肥胖。来自哈佛大学(HU)、马萨诸塞州总医院(MGH)、波兰科学院实验生物学Nencki研究所(Nencki Institute)的科学家们在华沙宣布在他们的小鼠实验中，有可能通过移植小数量的新生神经元到受损区域来重建脑功能。

Artur Czupryn医生（第一作者身份在Science杂志发表一篇论文）说“我们能获得的一个惊人的脑修复效果是显著降低遗传缺陷肥胖鼠的体重，而且进一步降低糖尿病的严重并发症。”

医学界已经长时间尝试通过移植干细胞修补局部损伤的脑组织。但这种措施是危险的，因为移植的干细胞经常是无序生长，而这种生长方式通常能导致癌症发生。

在哈佛大学(HU)、马萨诸塞州总医院(MGH)、波兰科学院实验生物学Nencki研究所(Nencki Institute)，这项科研已经进行了5年。它的目的是证实移植小数量的细胞能重建缺损的神经元回路、修复丧失的脑功能。缺乏廋素受体的遗传障碍鼠已经被用于这些实验。廋素是进食时，脂肪组织分泌到血液中的一种蛋白。当它到达下丘脑，将特异性与神经元发生反应。它的存在与否或者水平低下可分别导致饱胀或饥饿感。廋素受体缺乏的小鼠不知道饱胀感。它们的体重是健康小鼠的两倍且出现严重糖尿病。

来自哈佛大学和Nencki协会的研究团队的科研目标集中在未成熟神经元（神经母细胞）和祖神经元的移植。这两类细胞是特异的神经干细胞且已经确定了分化发生的方向。它们是从正在发育、健康鼠的胚胎大脑的小块组织中分离、获得并用于移植。因此当导入受体的脑中，这些细胞转变为神经元或伴行的胶质细胞的可能性增加。

通常情况下，被移植的细胞打数百万。但是在这科研项目中，科学家注入仅仅数千个神经元前体和神经母细胞的混悬液到鼠的下丘脑。以低侵袭性的方法（用一纤细的微量加液器其直径仅数倍于单细胞），
约300纳升细胞悬液被注入鼠下丘脑，

Czupryn医生说：“这混悬液被导入严格定义的鼠的下丘脑区域，该区域测量长度约200－400微米。我们能够定位精确是因为操作是在一独特的高分辨率的超声显微镜下引导（该设备在哈佛大学）。它能让我们进行复杂的无侵袭的显微植入且无以伦比的精确，就是因为我们能对脑部结构以及所导入的微量加液器进行高分辨率的影像扫描。

所有移植细胞均已标记上荧光蛋白，这使跟踪它们成为可能。操作完成后20多周，观察显示几乎一半的移植细胞转变为具有典型形态的神经元，产生了正常神经元特征性蛋白。通过应用尖端研究技术，或许能显示在大脑中心区域且功能为控制饥饿和饱胀的脑组织内部，缺损的多类型神经元被修复的全过程。而且新的神经元已经形成突触，并与脑部其他神经元发生联系，以及能对廋素、血糖、胰岛素水平改变产生正常的反应。

重建了鼠下丘脑的正常功能的最终的证据是通过测量体重和血液代谢指标获得的。与遗传缺陷障碍鼠这一对照群体不同，移植神经元的鼠体重类似正常鼠体重，且逆转异常改变的血代谢性指标也能被观察。

Czupryn总结到：“至今，对于移植细胞到大脑，许多尝试已经被描述在文献中。我们的结果已经显示移植非常少的神经母细胞和神经元祖细胞能重建毁坏的脑组织区域和影响整个机体组织。我们的结果显示可能植入新的、功能正常的神经元，它就能很好地与周围神经组织结合并重建缺失的脑功能。而且这种方法显示是低侵袭性和安全，因为它不导致肿瘤形成。”
哈佛大学和Nencki研究所的研究团队所获得成果明确了一个有希望的研究方向，能导致新的修复方法的产生。这项新方法有助于，如减少卒中后遗症或者提高帕金森（一种明确脑区域的功能障碍疾病）的治疗水平。但是科学家强调：基于他们的思路所产生的治疗手段在应用在临床、医院前，还需要数年实验、研究和监测。

2011-11-27 00:19

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