2024年12月6日 (五) 17:43的版本

神经元微环境

本页英文内容取自：经典教材医学生理学（第三版） (Medical Physiology, 3rd Edtion, Walter F Boron, published in 2016)

中文内容由 BH1RBH (Jack Tan) 粗糙翻译

蓝色 【注】 后内容为 BH1RBH (Jack Tan) 所加之注释

1 概述

1.1 大脑细胞外液为中枢神经元提供了高度调节的环境

Extracellular fluid in the brain provides a highly regulated environment for central nervous system neurons

Everything that surrounds individual neurons can be considered part of the neuronal microenvironment. Technically, therefore, the neuronal microenvironment includes the extracellular fluid (ECF), capillaries, glial cells, and adjacent neurons. Although the term often is restricted to just the immediate ECF, the ECF cannot be meaningfully discussed in isolation because of its extensive interaction with brain capillaries, glial cells, and cerebrospinal fluid (CSF). How the microenvironment interacts with neurons and how the brain (used here synonymously with central nervous system, or CNS) stabilizes it to provide constancy for neuronal function are the subjects of this discussion.

围绕单个神经元的一切都可以被认为是神经元微环境的一部分。因此，从技术上讲，神经元微环境包括细胞外液 （ECF）、毛细血管、神经胶质细胞和相邻的神经元。尽管该术语通常仅限于直接的 ECF，但由于 ECF 与脑毛细血管、神经胶质细胞和脑脊液 （CSF） 的广泛相互作用，因此不能单独有意义地讨论 ECF。微环境如何与神经元相互作用以及大脑（此处与中枢神经系统或 CNS 同义）如何稳定它以为神经元功能提供稳定性是本次讨论的主题。

The concentrations of solutes in brain extracellular fluid (BECF) fluctuate with neural activity, and conversely, changes in ECF composition can influence nerve cell behavior. Not surprisingly, therefore, the brain carefully controls the composition of this important compartment. It does so in three major ways: First, the brain uses the blood-brain barrier (BBB) to protect the BECF from fluctuations in blood composition. Second, the CSF, produced by choroid plexus epithelial cells, strongly influences the composition of the BECF. Third, the surrounding glial cells “condition” the BECF.

脑细胞外液 （BECF） 中溶质的浓度随神经活动而波动，相反，细胞外液 (ECF) 组成的变化会影响神经细胞的行为。因此，大脑小心翼翼地控制着这个重要隔室的组成也就不足为奇了。它主要通过三种方式做到这一点：首先，大脑使用血脑屏障 （BBB） 来保护脑细胞外液 (BECF) 免受血液成分波动的影响。其次，由脉络丛上皮细胞产生的脑脊液 (CSF) 强烈影响脑细胞外液 (BECF) 的组成。第三，周围的神经胶质细胞 “调节” 脑细胞外液。

1.2 大脑在物理和代谢上都很脆弱

The brain is physically and metabolically fragile

The ratio of brain weight to body weight in humans is the highest in the animal kingdom. The average adult brain weight is ~1400 g in men and ~1300 g in women— approximately the same weight as the liver (see p. 944). This large and vital structure, which has the consistency of thick pudding, is protected from mechanical injury by a surrounding layer of bone and by the CSF in which it floats.

人类的脑重与体重之比是动物界最高的。男性成人的平均脑重为 ~1400 克，女性为 ~1300 克——与肝脏的重量大致相同（见第 944 页）。这个大而重要的结构具有厚布丁的稠度，周围的骨层和漂浮在其中的脑脊液 (CSF) 可以保护它免受机械损伤。

The brain is also metabolically fragile. This fragility arises from its high rate of energy consumption, absence of significant stored fuel in the form of glycogen (~5% of the amount in the liver), and rapid development of cellular damage when ATP is depleted. However, the brain is not the greediest of the body’s organs; both the heart and kidney cortex have higher metabolic rates. Nevertheless, although it constitutes only 2% of the body by weight, the brain receives ~15% of resting blood flow and accounts for ~20% and 50% of total resting oxygen and glucose utilization, respectively. The brain’s high metabolic demands arise from the need of its neurons to maintain the steep ion gradients on which neuronal excitability depends. In addition, neurons rapidly turn over their actin cytoskeleton. Neuroglial cells, the other major cells in the brain, also maintain steep transmembrane ion gradients. More than half of the energy consumed by the brain is directed to maintain ion gradients, primarily through operation of the Na-K pump (see pp. 115–117). An interruption of the continuous supply of oxygen or glucose to the brain results in rapid depletion of energy stores and disruption of ion gradients. Because of falling ATP levels in the brain, consciousness is lost within 10 seconds of a blockade in cerebral blood flow. Irreversible nerve cell injury can occur after only 5 to 10 minutes of interrupted blood flow.

大脑的新陈代谢也很脆弱。这种脆弱性源于其高能耗、缺乏以糖原形式储存的大量燃料（肝脏中量的 ~5%）以及当 ATP 耗尽时细胞损伤的快速发展。然而，大脑并不是身体器官中最贪婪的；心脏和肾脏皮层的代谢率都较高。然而，尽管它仅占身体重量的 2%，但大脑接收 ~15% 的静息血流量，分别占总静息氧和葡萄糖利用率的 ~20% 和 50%。大脑的高代谢需求源于其神经元需要维持神经元兴奋性所依赖的陡峭离子梯度。此外，神经元会迅速翻转其肌动蛋白细胞骨架。神经胶质细胞是大脑中的其他主要细胞，也保持陡峭的跨膜离子梯度。大脑消耗的能量中有一半以上用于维持离子梯度，主要是通过 Na-K 泵的操作（参见第 115-117 页）。大脑持续供应氧气或葡萄糖的中断会导致能量储存的快速耗尽和离子梯度的破坏。由于大脑中的 ATP 水平下降，意识在脑血流阻塞后的 10 秒内就会丧失。不可逆的神经细胞损伤可能在血流中断仅 5 到 10 分钟后发生。

2 脑脊液 (Cerebrospinal Fluid, CSF)

CEREBROSPINAL FLUID

2.1 脑脊液充满脑室和蛛网膜下腔

CSF fills the ventricles and subarachnoid space

2.2 大脑漂浮在脑脊液中，脑脊液起到减震器的作用

The brain floats in CSF, which acts as a shock absorber

2.3 脉络丛将脑脊液分泌到脑室中，蛛网膜颗粒吸收它

The choroid plexuses secrete CSF into the ventricles, and the arachnoid granulations absorb it

2.4 脉络丛的上皮细胞分泌脑脊液

The epithelial cells of the choroid plexus secrete the CSF

3 大脑细胞外间隙

BRAIN EXTRACELLULAR SPACE

3.1 神经元、神经胶质细胞和毛细血管在 CNS 中紧密堆积在一起

Neurons, glia, and capillaries are packed tightly together in the CNS

3.2 脑脊液与脑细胞外液 (BECF) 自由交流，从而稳定神经元微环境的组成

The CSF communicates freely with the BECF, which stabilizes the composition of the neuronal microenvironment

3.3 伴随神经活动的离子通量导致细胞外离子浓度发生较大变化

The ion fluxes that accompany neural activity cause large changes in extracellular ion concentration

4 血脑屏障 (BBB)

THE BLOOD-BRAIN BARRIER

4.1 血脑屏障阻止一些血液成分进入大脑细胞外间隙

The blood-brain barrier prevents some blood constituents from entering the brain extracellular space

4.2 连续的紧密连接连接大脑毛细血管内皮细胞

Continuous tight junctions link brain capillary endothelial cells

4.3 不带电和脂溶性分子更容易通过血脑屏障

Uncharged and lipid-soluble molecules more readily pass through the blood-brain barrier

4.4 毛细血管内皮细胞的运输有助于血脑屏障

Transport by capillary endothelial cells contributes to the blood-brain barrier

5 胶质细胞 (Glial Cells)

GLIAL CELLS

5.1 神经胶质细胞占大脑体积的一半，数量超过神经元

5.2 星形胶质细胞以乳酸的形式为神经元提供燃料

5.3 星形胶质细胞主要可渗透 K+，也有助于调节 [K+]o

5.4 间隙连接将星形胶质细胞彼此偶联，允许小溶质扩散

5.5 星形胶质细胞合成神经递质，从细胞外间隙吸收它们，并具有神经递质受体

5.6 星形胶质细胞分泌营养因子，促进神经元存活和突触发生

5.7 星形胶质细胞终足调节脑血流

5.8 少突胶质细胞和雪旺细胞制造并维持髓鞘

5.9 少突胶质细胞参与大脑中的 pH 调节和铁代谢

5.10 小胶质细胞是 CNS 的巨噬细胞

6 Reference

• Physiology
• Pharmacology
• Addiction
• BBB 血脑屏障概述

• Smith et al. Insights into inner ear function and disease through novel visualizatio of the ductus reuniens, a semila communication between hearing and balance mechanisms. JARO (2022)
• http://www.cochlea.eu/en/cochlea
• http://www.cochlea.eu/en/cochlea/cochlear-fluids