Ch11 The Neuronal Microenvironment
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
目录 |
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
CSF is a colorless, watery liquid. It fills the ventricles of the brain and forms a thin layer around the outside of the brain and spinal cord in the subarachnoid space. CSF is secreted within the brain by a highly vascularized epithelial structure called the choroid plexus and circulates to sites in the subarachnoid space, where it enters the venous blood system. The composition of CSF is highly regulated, and because it directly mixes with BECF, it helps regulate the composition of BECF. The choroid plexus can be thought of as the brain’s “kidney” in that it stabilizes the composition of CSF, just as the kidney stabilizes the composition of blood plasma.
CSF 是一种无色的水状液体。它充满大脑的心室，并在大脑外部和蛛网膜下腔的脊髓周围形成一层薄层。CSF 在大脑内由称为脉络丛的高度血管化的上皮结构分泌，并循环到蛛网膜下腔的部位，在那里进入静脉血系统。CSF 的成分受到高度调节，因为它直接与 BECF 混合，所以有助于调节 BECF 的成分。脉络丛可以被认为是大脑的“肾脏”，因为它稳定了脑脊液的组成，就像肾脏稳定血浆的组成一样。
2.1 脑脊液充满脑室和蛛网膜下腔
CSF fills the ventricles and subarachnoid space
The ventricles of the brain are four small compartments located within the brain (Fig. 11-1A). Each ventricle contains a choroid plexus and is filled with CSF. The ventricles are linked together by channels, or foramina, that allow CSF to move easily between them. The two lateral ventricles are the largest and are symmetrically located within the cerebral hemispheres. The choroid plexus of each lateral ventricle is located along the inner radius of this horseshoe-shaped structure (see Fig. 11-1B). The two lateral ventricles each communicate with the third ventricle, which is located in the midline between the thalami, through the two interventricular foramina of Monro. The choroid plexus of the third ventricle lies along the ventricle roof. The third ventricle communicates with the fourth ventricle by the cerebral aqueduct of Sylvius. The fourth ventricle is the most caudal ventricle and is located in the brainstem. It is bounded by the cerebellum superiorly and by the pons and medulla inferiorly. The choroid plexus of the fourth ventricle lies along only a portion of this ventricle’s tent-shaped roof. The fourth ventricle is continuous with the central canal of the spinal cord. CSF escapes from the fourth ventricle and flows into the subarachnoid space through three foramina: the two laterally placed foramina of Luschka and the midline opening in the roof of the fourth ventricle, called the foramen of Magendie. We shall see below how CSF circulates throughout the subarachnoid space of the brain and spinal cord, and how it moves through brain tissue itself.
大脑的心室是位于大脑内的四个小隔室（图 11-1A）。每个心室都包含一个脉络丛，并充满脑脊液。心室通过通道或孔连接在一起，使脑脊液能够在它们之间轻松移动。两个侧脑室最大，对称位于大脑半球内。每个侧脑室的脉络丛位于该马蹄形结构的内桡骨上（见图 11-1B）。两个侧脑室分别通过两个门罗室间孔与位于丘脑之间中线的第三脑室相通。第三脑室的脉络丛位于脑室顶部。第三脑室通过 Sylvius 的大脑导水管与第四脑室相通。第四脑室是最尾的脑室，位于脑干中。它上部以小脑为界，下部以脑桥和延髓为界。第四脑室的脉络丛仅位于该脑室帐篷形屋顶的一部分。第四脑室与脊髓中央管相连。CSF 从第四脑室逸出，通过三个孔流入蛛网膜下腔：两个外侧放置的 Luschka 孔和第四脑室顶部的中线开口，称为 Magendie 孔。我们将在下面看到 CSF 如何在大脑和脊髓的蛛网膜下腔中循环，以及它如何在脑组织本身中移动。
The brain and spinal cord are covered by two membranous tissue layers called the leptomeninges, which are in turn surrounded by a third, tougher layer. The innermost of these three layers is the pia mater; the middle is the arachnoid mater (or arachnoid membrane); and the outermost layer is the dura mater (Fig. 11-2). Between the arachnoid mater and pia mater (i.e., the leptomeninges) is the subarachnoid space, which is filled with CSF that flows from the fourth ventricle. The CSF in the subarachnoid space completely surrounds the brain and spinal cord. In adults, the subarachnoid space and the ventricles with which they are continuous contain ~150 mL of CSF, 30 mL in the ventricles and 120 mL in the subarachnoid spaces of the brain and spinal cord.
大脑和脊髓被两层称为软脑膜的膜组织层覆盖，而软脑膜又被第三层更坚韧的组织层包围。这三层中最里面的是软脑膜;中间是蛛网膜（或蛛网膜）;最外层是硬脑膜（图 11-2）。蛛网膜和软脑膜（即软脑膜）之间是蛛网膜下腔，它充满了从第四脑室流出的脑脊液。蛛网膜下腔的 CSF 完全围绕着大脑和脊髓。在成人中，蛛网膜下腔及其连续的脑室含有 ~150 mL 的脑脊液，脑室中含有 30 mL，大脑和脊髓的蛛网膜下腔中含有 120 mL。
The pia mater (Latin for “tender mother”) is a thin layer of connective tissue cells that is very closely applied to the surface of the brain and covers blood vessels as they plunge through the arachnoid into the brain. A nearly complete layer of astrocytic endfeet (see p. 286)—the glia limitans— abuts the pia from the brain side and is separated from the pia by a basement membrane. The pia adheres so tightly to the associated glia limitans in some areas that the two seem to be continuous with each other; this combined structure is sometimes called the pial-glial membrane or layer. This layer does not restrict diffusion of substances between the BECF and the CSF.
pia mater（拉丁语为“温柔的母亲”）是一层薄薄的结缔组织细胞，非常紧密地贴在大脑表面，并在血管通过蛛网膜进入大脑时覆盖血管。几乎完整的星形胶质细胞终足层（见第 286 页）——极限胶质细胞——从大脑一侧紧邻软脑膜，并通过基底膜与软脑膜隔开。软脑膜在某些区域与相关的神经胶质限制素紧密粘附，以至于两者似乎彼此连续;这种组合结构有时称为软脑膜-胶质细胞膜或层。该层不限制物质在 BECF 和 CSF 之间的扩散。
The arachnoid membrane (from the Greek arachnoeides [cobweb-like]) is composed of layers of cells, resembling those that make up the pia, linked together by tight junctions. The arachnoid isolates the CSF in the subarachnoid space from blood in the overlying vessels of the dura mater. The cells that constitute the arachnoid and the pia are continuous in the trabeculae that span the subarachnoid space. These arachnoid and pial layers are relatively avascular; thus, the leptomeningeal cells that form them probably derive nutrition from the CSF that they enclose as well as from the ECF that surrounds them. The leptomeningeal cells can phagocytose foreign material in the subarachnoid space.
蛛网膜（来自希腊语 arachnoeides [蜘蛛网状]）由细胞层组成，类似于构成软脑膜的细胞，通过紧密的连接连接在一起。蛛网膜将蛛网膜下腔的 CSF 与硬脑膜上覆血管中的血液分离出来。构成蛛网膜和软脑膜的细胞在跨越蛛网膜下腔的小梁中是连续的。这些蛛网膜和软脑膜层相对无血管;因此，形成它们的软脑膜细胞可能从它们所包围的 CSF 以及它们周围的 ECF 中获取营养。软脑膜细胞可以吞噬蛛网膜下腔中的异物。
The dura mater is a thick, inelastic membrane that forms an outer protective envelope around the brain. The dura has two layers that split to form the intracranial venous sinuses. Blood vessels in the dura mater are outside the BBB (see below), and substances could easily diffuse from dural capillaries into the nearby CSF if it were not for the blood-CSF barrier created by the arachnoid.
硬脑膜是一层厚的、无弹性的膜，在大脑周围形成一个外部保护膜。硬脑膜有两层，它们分裂形成颅内静脉窦。硬脑膜中的血管位于 BBB 之外（见下文），如果不是蛛网膜形成的血液-CSF 屏障，物质很容易从硬脑膜毛细血管扩散到附近的 CSF。
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
An important function of CSF is to buffer the brain from mechanical injury. The CSF that surrounds the brain reduces the effective weight of the brain from ~1400 g to <50 g. This buoyancy is a consequence of the difference in the specific gravities of brain tissue (1.040) and CSF (1.007). The mechanical buffering that the CSF provides greatly diminishes the risk of acceleration-deceleration injuries in the same way that wearing a bicycle helmet reduces the risk of head injury. As you strike a tree, the foam insulation of the helmet gradually compresses and reduces the velocity of your head. Thus, the deceleration of your head is not nearly as severe as the deceleration of the outer shell of your helmet. The importance of this fluid suspension system is underscored by the consequences of reduced CSF pressure, which sometimes happens transiently after the diagnostic procedure of removal of CSF from the spinal subarachnoid space (Box 11-1). Patients with reduced CSF pressure experience severe pain when they try to sit up or stand because the brain is no longer cushioned by shock-absorbing fluid and small gravity-induced movements put strain on pain-sensitive structures. Fortunately, the CSF leak that can result from lumbar puncture is only temporary; the puncture hole easily heals itself, with prompt resolution of all symptoms.
CSF 的一个重要功能是缓冲大脑免受机械损伤。围绕大脑的 CSF 将大脑的有效重量从 ~1400 克降低到 <50 克。这种浮力是脑组织 （1.040） 和 CSF （1.007） 比重差异的结果。CSF 提供的机械缓冲大大降低了加速-减速损伤的风险，就像佩戴自行车头盔可以降低头部受伤的风险一样。当您撞到一棵树时，头盔的泡沫绝缘材料会逐渐压缩并降低头部的速度。因此，头部的减速并不像头盔外壳的减速那么严重。这种液体悬浮系统的重要性因降低 CSF 压力的后果而得到强调，这有时会在从脊髓蛛网膜下腔去除 CSF 的诊断程序后短暂发生（框 11-1）。脑脊液压力降低的患者在尝试坐起来或站起来时会感到剧烈疼痛，因为大脑不再被减震液缓冲，而重力诱导的小运动会对疼痛敏感结构造成压力。幸运的是，腰椎穿刺可能导致的脑脊液漏只是暂时的;穿刺孔很容易自愈，所有症状都能迅速消退。
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
Total CSF production is ~500 mL/day. Because the entire volume of CSF is ~150 mL, the CSF “turns over” about three times each day. Most of the CSF is produced by the choroid plexuses, which are present in four locations (see Fig. 11-1): the two lateral ventricles, the third ventricle, and the fourth ventricle. The capillaries within the brain appear to form as much as 30% of the CSF.
CSF 总产量为 ~500 mL/天。因为 CSF 的整个体积为 ~150 mL，所以 CSF 每天大约“翻转”3 次。大部分脑脊液由脉络丛产生，脉络丛存在于四个位置（见图 11-1）：两个侧脑室、第三脑室和第四脑室。大脑内的毛细血管似乎构成了多达 30% 的 CSF。
Secretion of new CSF creates a slight pressure gradient, which drives the circulation of CSF from its ventricular sites of origin into the subarachnoid space through three openings in the fourth ventricle, as discussed above. CSF percolates throughout the subarachnoid space and is finally absorbed into venous blood in the superior sagittal sinus, which lies between the two cerebral hemispheres (see Fig. 11-2). The sites of absorption are specialized evaginations of the arachnoid membrane into the venous sinus (Fig. 11-3A). These absorptive sites are called pacchionian granulations N11-1 or simply arachnoid granulations when they are large (up to 1 cm in diameter) and arachnoid villi if their size is microscopic. These structures act as pressuresensitive one-way valves for bulk CSF clearance; CSF can cross into venous blood but venous blood cannot enter CSF. The actual mechanism of CSF absorption may involve transcytosis (see pp. 477–487), or the formation of giant fluidcontaining vacuoles that cross from the CSF side of the arachnoid epithelial cells to the blood side (see Fig. 11-3A). CSF may also be absorbed into spinal veins from herniations of arachnoid cells into these venous structures.
如上所述，新脑脊液的分泌会产生轻微的压力梯度，这驱动脑脊液从其起源的心室部位循环到蛛网膜下腔，通过第四脑室的三个开口。CSF 渗透到整个蛛网膜下腔，最后被吸收到位于两个大脑半球之间的矢状窦上部的静脉血中（见图 11-2）。吸收部位是蛛网膜专门逃逸到静脉窦中（图 11-3A）。这些吸收部位称为 PACCHIONIAN 颗粒 N11-1，当它们较大（直径可达 1 cm）时简称为蛛网膜颗粒，如果它们的大小是微观的，则简称为蛛网膜绒毛。这些结构充当用于大量 CSF 清除的压敏单向阀;CSF 可以进入静脉血，但静脉血不能进入 CSF。CSF 吸收的实际机制可能涉及转胞吞作用（参见第 477-487 页），或形成从蛛网膜上皮细胞的 CSF 侧穿过血液侧的含液巨大液泡（参见图 11-3A）。CSF 也可能从蛛网膜细胞疝吸收到脊髓静脉中，进入这些静脉结构。
The pressure of the CSF, which is higher than that of the venous blood, promotes net CSF movement into venous blood. When intracranial pressure (equivalent to CSF pressure) exceeds ~70 mm H2O, absorption commences and increases in a graded fashion with further intracranial pressure (see Fig. 11-3B). In contrast to CSF absorption, CSF formation is not sensitive to intracranial pressure. This arrangement helps stabilize intracranial pressure. Thus, if intracranial pressure increases, CSF absorption selectively increases as well, so that absorption exceeds formation. This response lowers CSF volume and tends to counteract the increased intracranial pressure. However, if absorption of CSF is impaired even at an initially normal intracranial pressure (Box 11-2), CSF volume increases and causes an increase in intracranial pressure, which can lead to a disturbance in brain function.
CSF 的压力高于静脉血的压力，促进 Net CSF 进入静脉血。当颅内压（相当于 CSF 压力）超过 ~70 mm H2O 时，吸收开始并随着颅内压的进一步而逐渐增加（见图 11-3B）。与 CSF 吸收相反，CSF 形成对颅内压不敏感。这种安排有助于稳定颅内压。因此，如果颅内压升高，CSF 吸收也会选择性增加，从而使吸收超过形成。这种反应会降低 CSF 体积，并倾向于抵消增加的颅内压。然而，如果在最初正常的颅内压下，脑脊液的吸收也受损（框 11-2），脑脊液体积增加并导致颅内压升高，这可能导致脑功能紊乱。
Some subarachnoid CSF flows into “sleeves” around arteries that dive from the subarachnoid space (see Fig. 11-2) deeply into the substance of the brain. This CSF appears to exit the sleeve by flowing across the pia/glia limitans and into brain extracellular space (BECS), where it mixes with BECF. Moving by convection, the BECF eventually appears to cross the pia/glia limitans that surrounds veins, enter via perivenous sleeves, and return to the subarachnoid space. This parenchymal CSF circuit—termed the glymphatic system N11-2—may be an efficient pathway to rid the brain of extracellular debris, including glutamate and potentially dangerous peptides such as amyloid beta.
一些蛛网膜下腔 CSF 流入动脉周围的“袖子”，这些动脉从蛛网膜下腔（见图 11-2）深入大脑物质。这种 CSF 似乎通过流经 pia/神经胶质限制体进入大脑细胞外空间 （BECS） 而离开袖状物，在那里它与 BECF 混合。通过对流移动，BECF 最终似乎穿过围绕静脉的软脑膜/神经胶质限制体，通过静脉周围袖状进入，并返回蛛网膜下腔。这种实质 CSF 回路（称为淋巴系统 N11-2）可能是清除大脑细胞外碎片（包括谷氨酸和潜在危险肽，如 β 淀粉样蛋白）的有效途径。
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
Each of the four choroid plexuses is formed during embryological development by invagination of the tela choroidea into the ventricular cavity (Fig. 11-4). The tela choroidea consists of a layer of ependymal cells covered by the pia mater and its associated blood vessels. The choroid epithelial cells (see Fig. 11-4, first inset) are specialized ependymal cells and therefore contiguous with the ependymal lining of the ventricles at the margins of the choroid plexus. Choroid epithelial cells are cuboidal and have an apical border with microvilli and cilia that project into the ventricle (i.e., into the CSF). The plexus receives its blood supply from the anterior and posterior choroidal arteries; blood flow to the plexuses—per unit mass of tissue—is ~10-fold greater than the average cerebral blood flow. Sympathetic and parasympathetic nerves innervate each plexus, and sympathetic input appears to inhibit CSF formation. A high density of relatively leaky capillaries is present within each plexus; as discussed below, these capillaries are outside the BBB. The choroid epithelial cells are bound to one another by tight junctions that completely encircle each cell, an arrangement that makes the epithelium an effective barrier to free diffusion. Thus, although the choroid capillaries are outside the BBB, the choroid epithelium insulates the ECF around these capillaries (which has a composition more similar to that of arterial blood) from the CSF. Moreover, the thin neck that connects the choroid plexus to the rest of the brain isolates the ECF near the leaky choroidal capillaries from the highly protected BECF in the rest of the brain.
四个脉络丛中的每一个都是在胚胎发育过程中通过将 tela 绒毛膜内陷到心室腔中形成的（图 11-4）。tela choroidea 由一层室管膜细胞组成，该细胞被软脑膜及其相关血管覆盖。脉络膜上皮细胞（见图 11-4，第一插图）是专门的室管膜细胞，因此与脉络丛边缘的室管膜衬里相邻。脉络膜上皮细胞是立方体的，顶端边界有微绒毛和纤毛，伸入脑室（即脑脊液）。神经丛从脉络膜前动脉和后脉络膜动脉接收血液供应;流向神经丛的血流量（每单位质量的组织）比平均脑血流量大 ~10 倍。交感神经和副交感神经支配每个神经丛，交感神经输入似乎抑制了 CSF 的形成。每个神经丛内都存在高密度的相对渗漏的毛细血管;如下所述，这些毛细血管位于 BBB 之外。脉络膜上皮细胞通过完全包围每个细胞的紧密连接相互结合，这种排列使上皮成为自由扩散的有效屏障。因此，尽管脉络膜毛细血管位于 BBB 之外，但脉络膜上皮将这些毛细血管周围的 ECF（其成分更类似于动脉血的成分）与 CSF 隔离开来。此外，将脉络丛与大脑其他部分相连的细颈将渗漏的脉络膜毛细血管附近的 ECF 与大脑其他部分高度受保护的 BECF 隔离开来。
The composition of CSF differs considerably from that of plasma; thus, CSF is not just an ultrafiltrate of plasma (Table 11-1). For example, CSF has lower concentrations of K+ and amino acids than plasma does, and it contains almost no protein. Moreover, the choroid plexuses rigidly maintain the concentration of ions in CSF in the face of large swings in ion concentration in plasma. This ion homeostasis includes K+, H+ /HCO3−, Mg2+, Ca2+, and, to a lesser extent, Na+ and Cl−. All these ions can affect neural function, hence the need for tight homeostatic control. The neuronal microenvironment is so well protected from the blood by the choroid plexuses and the rest of the BBB that essential micronutrients, such as vitamins and trace elements that are needed in very small amounts, must be selectively transported into the brain. Some of these micronutrients are transported into the brain primarily by the choroid plexus and others primarily by the endothelial cells of the blood vessels. In comparison, the brain continuously metabolizes relatively large amounts of “macronutrients,” such as glucose and some amino acids. CSF forms in two sequential stages. First, ultrafiltration of plasma occurs across the fenestrated capillary wall (see p. 462) into the ECF beneath the basolateral membrane of the choroid epithelial cell. Second, choroid epithelial cells secrete fluid into the ventricle. CSF production occurs with a net transfer of NaCl and NaHCO3 that drives water movement isosmotically (see Fig. 11-4, right inset, large white arrow labeled “Transepithelial fluxes”). The renal proximal tubule (see p. 761) and small intestine (see p. 903) also perform near-isosmotic transport, but in the direction of absorption rather than secretion. In addition, the choroid plexus conditions CSF by absorbing K+ (see Fig. 11-4, right inset, thin black arrow labeled “Transepithelial fluxes”) and certain other substances (e.g., 5-hydroxyindoleacetic acid, a metabolite of serotonin).
CSF 的成分与血浆的成分有很大不同;因此，CSF 不仅仅是血浆的超滤液（表 11-1）。例如，CSF 的 K+ 和氨基酸浓度低于血浆，并且几乎不含蛋白质。此外，面对血浆中离子浓度的大幅波动，脉络丛刚性地保持 CSF 中离子的浓度。这种离子稳态包括 K+、H+ /HCO3−、Mg2+、Ca2+，以及较小程度的 Na+ 和 Cl−。所有这些离子都会影响神经功能，因此需要严格的稳态控制。神经元微环境受到脉络丛和 BBB 其余部分的良好保护，不受血液的影响，因此必须选择性地将必需的微量营养素，例如非常少量所需的维生素和微量元素输送到大脑中。其中一些微量营养素主要通过脉络丛运输到大脑中，而另一些主要通过血管的内皮细胞运输。相比之下，大脑不断代谢相对大量的“宏量营养素”，例如葡萄糖和一些氨基酸。CSF 分两个连续阶段形成。首先，血浆超滤穿过有孔毛细血管壁（见第 462 页）进入脉络膜上皮细胞基底外侧膜下的 ECF。其次，脉络膜上皮细胞将液体分泌到心室中。CSF 的产生是通过 NaCl 和 NaHCO3 的净转移发生的，该转移驱动水的同向运动（参见图 11-4，右插图，标记为“跨上皮通量”的白色大箭头）。肾近端小管（见第 761 页）和小肠（见第 903 页）也进行近等渗运输，但方向是吸收而不是分泌。此外，脉络丛通过吸收 K+（见图 11-4，右插图，标记为“跨上皮通量”的黑色细箭头）和某些其他物质（例如，5-羟基吲哚乙酸，5-羟色胺的代谢物）来调节 CSF。
The upper portion of the right inset of Figure 11-4 summarizes the ion transport processes that mediate CSF secretion. The net secretion of Na+ from plasma to CSF is a two-step process. The Na-K pump in the choroid plexus, unlike that in other epithelia (see pp. 137–138), is unusual in being located on the apical membrane, where it moves Na+ out of the cell into the CSF—the first step. This active movement of Na+ out of the cell generates an inward Na+ gradient across the basolateral membrane, energizing basolateral Na+ entry—the second step—through Na-H exchange and Na+- coupled HCO3− transport. In the case of Na-H exchange, the limiting factor is the availability of intracellular H+, which carbonic anhydrase generates, along with HCO3− , from CO2 and H2O. Thus, blocking of the Na-K pump with ouabain halts CSF formation, whereas blocking of carbonic anhydrase with acetazolamide slows CSF formation.
图 11-4 右插图的上半部分总结了介导 CSF 分泌的离子传输过程。Na+ 从血浆到 CSF 的净分泌是一个两步过程。与其他上皮细胞不同（参见第 137-138 页），脉络丛中的 Na-K 泵不寻常，它位于顶膜上，它将 Na+ 从细胞中移出进入 CSF——第一步。Na+ 的这种主动运动出细胞，在基底外侧膜上产生向内的 Na + 梯度，通过 Na-H 交换和 Na + 偶联的 HCO3 − 转运，为基底外侧 Na + 进入提供动力，这是第二步。在 Na-H 交换的情况下，限制因素是细胞内 H+ 的可用性，碳酸酐酶与 HCO3− 一起从 CO2 和 H2O 中产生。因此，用哇巴因阻断 Na-K 泵会阻止 CSF 形成，而用乙酰唑胺阻断碳酸酐酶会减慢 CSF 的形成。
The net secretion of Cl−, like that of Na+, is a two-step process. The first step is the intracellular accumulation of Cl− by the basolateral Cl-HCO3 exchanger. Note that the net effect of parallel Cl-HCO3 exchange and Na-H exchange is NaCl uptake. The second step is efflux of Cl− across the apical border into the CSF through either a Cl− channel or a K/Cl cotransporter.
Cl− 的净分泌与 Na+ 一样，是一个两步过程。第一步是基底外侧 Cl-HCO3 交换剂在细胞内积累 Cl−。请注意，平行 Cl-HCO3 交换和 Na-H 交换的净效应是 NaCl 摄取。第二步是 Cl− 通过 Cl− 通道或 K/Cl 协同转运蛋白穿过顶端边界流入 CSF。
HCO3− secretion into CSF is important for neutralizing acid produced by CNS cells. At the basolateral membrane, the epithelial cell probably takes up HCO3− directly from the plasma filtrate through electroneutral Na/HCO3 cotransporters (see Fig. 5-11F) and the Na+-driven Cl-HCO3 exchanger (see Fig. 5-13C). As noted before, HCO3− can also accumulate inside the cell after CO2 entry. The apical step, movement of intracellular HCO3− into the CSF, probably occurs by an electrogenic Na/HCO3 cotransporter (see Fig. 5-11D) and Cl− channels (which may be permeable to HCO3−).
HCO3− 分泌到 CSF 中对于中和 CNS 细胞产生的酸很重要。在基底外侧膜，上皮细胞可能通过电中性 Na/HCO3 协同转运蛋白（见图 5-11F）和 Na+ 驱动的 Cl-HCO3 交换蛋白（见图 5-13C）直接从血浆滤液中吸收 HCO3−。如前所述，HCO3− 在 CO2 进入后也会在细胞内积累。顶端步骤，即细胞内 HCO3− 向 CSF 的运动，可能是由电生 Na/HCO3 协同转运蛋白（见图 5-11D）和 Cl− 通道（可能对 HCO3− 具有渗透性）发生的。
The lower portion of the right inset of Figure 11-4 summarizes K+ absorption from the CSF. The epithelial cell takes up K+ by the Na-K pump and the Na/K/Cl cotransporter at the apical membrane (see Fig. 5-11G). Most of the K+ recycles back to the CSF, but a small amount exits across the basolateral membrane and enters the blood. The concentration of K+ in freshly secreted CSF is ~3.3 mM. Even with very large changes in plasma [K+], the [K+] in CSF changes very little. The value of [K+] in CSF is significantly lower in the subarachnoid space than in choroid secretions, which suggests that brain capillary endothelial cells remove extracellular K+ from the brain.
图 11-4 右侧插图的下半部分总结了 CSF 的 K+ 吸收。上皮细胞被 Na-K 泵和顶膜上的 Na/K/Cl 协同转运蛋白吸收 K+（见图 5-11G）。大部分 K+ 循环回到 CSF，但有一小部分穿过基底外侧膜流出并进入血液。新鲜分泌的 CSF 中 K+ 的浓度为 ~3.3 mM。即使血浆 [K+] 的变化非常大，CSF 中的 [K+] 变化也很小。蛛网膜下腔 CSF 中 [K+] 的值明显低于脉络膜分泌物，这表明脑毛细血管内皮细胞从大脑中去除细胞外 K+。
Water transport across the choroid epithelium is driven by a small osmotic gradient favoring CSF formation. This water movement is facilitated by the water channel aquaporin 1 (AQP1; see p. 110) on both the apical and basal membranes as in the renal proximal tubule (see pp. 761–762).
水通过脉络膜上皮的运输是由有利于 CSF 形成的小渗透压梯度驱动的。与肾近端小管一样，顶端和基底膜上的水通道水通道蛋白 1（AQP1;见第 110 页）促进了这种水的运动（见第 761-762 页）。
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
The average width of the space between brain cells is ~20 nm, which is about three orders of magnitude smaller than the diameter of either a neuron or a glial cell body (Fig. 11-5). However, because the surface membranes of neurons and glial cells are highly folded (i.e., have a large surface-to- volume ratio), the BECF in toto has a sizable volume fraction, ~20%, of total brain volume. The fraction of the brain occupied by BECF varies somewhat in different areas of the CNS and increases during sleep. Moreover, because brain cells can increase volume rapidly during intense neural activity, the BECF fraction can reversibly decrease within seconds from ~20% to ~17% of brain volume.
脑细胞之间空间的平均宽度为 ~20 nm，比神经元或神经胶质细胞体的直径小约三个数量级（图 11-5）。然而，由于神经元和神经胶质细胞的表面膜高度折叠（即具有较大的表面积与体积比），因此 toto 中的 BECF 具有相当大的体积分数，占总脑体积的 ~20%。BECF 占据的大脑部分在 CNS 的不同区域略有不同，并在睡眠期间增加。此外，由于脑细胞可以在强烈的神经活动期间迅速增加体积，因此 BECF 分数可以在几秒钟内从脑体积的 ~20% 可逆地降低到 ~17%。
Even though the space between brain cells is extremely small, diffusion of ions and other solutes within this thin BECF space is reasonably high. However, a particle that diffuses through the BECF from one side of a neuron to the other must take a circuitous route that is described by a parameter called tortuosity. For a normal width of the cell-to-cell spacing, this tortuosity reduces the rate of diffusion by ~60% compared with movement in free solution. Decreases in cell-to-cell spacing can further slow diffusion. For example, brain cells, especially glial cells, swell under certain pathological conditions and sometimes with intense neural activity. Cell swelling is associated with a reduction in BECF because water moves from the BECF into cells. The intense cell swelling associated with acute anoxia, for example, can reduce BECF volume from ~20% to ~5% of total brain volume. By definition, this reduced extracellular volume translates to reduced cell-to-cell spacing, which further slows the extracellular movement of solutes between the blood and brain cells (Box 11-3).
尽管脑细胞之间的空间非常小，但离子和其他溶质在这个薄的 BECF 空间内的扩散相当高。然而，通过 BECF 从神经元的一侧扩散到另一侧的粒子必须采用由称为迂曲度的参数描述的迂回路线。对于细胞间间距的正常宽度，与自由溶液中的移动相比，这种弯曲使扩散速率降低了 ~60%。细胞间间距的减小会进一步减慢扩散。例如，脑细胞，尤其是神经胶质细胞，在某些病理条件下会肿胀，有时还会伴有强烈的神经活动。细胞肿胀与 BECF 的减少有关，因为水从 BECF 进入细胞。例如，与急性缺氧相关的强烈细胞肿胀可以将 BECF 体积从总脑体积的 ~20% 降低到 ~5%。根据定义，这种细胞外体积的减少转化为细胞间间距的减小，这进一步减慢了溶质在血液和脑细胞之间的细胞外运动（框 11-3）。
The BECF is the route by which important molecules such as oxygen, glucose, and amino acids reach brain cells and by which the products of metabolism, including CO2 and catabolized neurotransmitters, leave the brain. The BECF also permits molecules that are released by brain cells to diffuse to adjacent cells. Neurotransmitter molecules released at synaptic sites, for example, can spill over from the synaptic cleft and contact nearby glial cells and neurons, in addition to their target postsynaptic cell. Glial cells express neurotransmitter receptors, and neurons have extrajunctional receptors; therefore, these cells are capable of receiving “messages” sent through the BECF. Numerous trophic molecules (see p. 292) secreted by brain cells diffuse in the BECF to their targets. Intercellular communication by way of the BECF is especially well suited for the transmission of tonic signals that are ideal for longer-term modulation of the behavior of aggregates of neurons and glial cells. The chronic presence of variable amounts of neurotransmitters in the BECF supports this idea.
BECF 是氧、葡萄糖和氨基酸等重要分子到达脑细胞的途径，以及包括 CO2 和分解代谢的神经递质在内的新陈代谢产物离开大脑的途径。BECF 还允许脑细胞释放的分子扩散到邻近细胞。例如，在突触部位释放的神经递质分子可以从突触间隙溢出，除了接触目标突触后细胞外，还可以接触附近的神经胶质细胞和神经元。神经胶质细胞表达神经递质受体，神经元具有连接外受体;因此，这些信元能够接收通过 BECF 发送的 “消息”。脑细胞分泌的许多营养分子（见第 292 页）在 BECF 中扩散到其目标。通过 BECF 进行的细胞间通讯特别适合于强直信号的传输，这些信号非常适合长期调节神经元和神经胶质细胞聚集体的行为。BECF 中长期存在不同数量的神经递质支持了这一想法。
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
CSF in the ventricles and the subarachnoid space can exchange freely with BECF across two borders, the pia mater and ependymal cells. The pial-glial membrane (see Fig. 11-2, upper inset) has paracellular gaps through which substances can equilibrate between the subarachnoid space and BECF. Ependymal cells (see Fig. 11-2, lower inset) are special glial cells that line the walls of the ventricles and form the cellular boundary between the CSF and the BECF. These cells form gap junctions (see p. 45) between themselves that mediate intercellular communication, but they do not create a tight epithelium (see p. 137). Thus, macromolecules and ions can also easily pass through this cellular layer through paracellular openings (some notable exceptions to this rule are considered below) and equilibrate between the CSF in the ventricle and the BECF.
脑室和蛛网膜下腔的 CSF 可以跨越软脑膜和室管膜细胞两个边界与 BECF 自由交换。软脑膜-胶质膜（见图 11-2，上插图）具有细胞旁间隙，物质可以通过这些间隙在蛛网膜下腔和 BECF 之间保持平衡。室管膜细胞（见图 11-2，下插图）是特殊的神经胶质细胞，排列在脑室壁上，形成 CSF 和 BECF 之间的细胞边界。这些细胞在它们之间形成间隙连接（见第 45 页），介导细胞间通讯，但它们不会形成紧密的上皮（见第 137 页）。因此，大分子和离子也可以很容易地通过细胞旁开口穿过该细胞层（下面将考虑此规则的一些显着例外）并在心室中的 CSF 和 BECF 之间达到平衡。
Because CSF and BECF can readily exchange with one another, it is not surprising that they have a similar chemical composition. For example, [K+] is ~3.3 mM in freshly secreted CSF and ~3 mM in both the CSF of the subarachnoid space (see Table 11-1) and BECF. The [K+] of blood is ~4.5 mM. However, because of the extent and vast complexity of the extracellular space, changes in the composition of CSF are reflected slowly in the BECF and probably incompletely.
因为 CSF 和 BECF 可以很容易地相互交换，所以它们具有相似的化学成分也就不足为奇了。例如，[K+] 在新鲜分泌的 CSF 中为 ~3.3 mM，在蛛网膜下腔的 CSF 中为 ~3 mM（见表 11-1）和 BECF。血液的 [K+] 为 ~4.5 mM。然而，由于细胞外空间的范围和巨大复杂性，CSF 组成的变化在 BECF 中反映得很慢，而且可能不完全。
CSF is an efficient waste-management system because of its high rate of production, its circulation over the surface of the brain, and the free exchange between CSF and BECF. Products of metabolism and other substances released by cells, perhaps for signaling purposes, can diffuse into the chemically stable CSF and ultimately be removed on a continuous basis either by bulk resorption into the venous sinuses or by active transport across the choroid plexus into the blood. For example, the choroid plexus actively absorbs the breakdown products of the neurotransmitters serotonin (i.e., 5-hydroxyindoleacetic acid) and dopamine (i.e., homovanillic acid).
CSF 是一种高效的废物管理系统，因为它的生产率高，在大脑表面循环，以及 CSF 和 BECF 之间的自由交换。细胞释放的新陈代谢产物和其他物质，可能出于信号传输目的，可以扩散到化学稳定的 CSF 中，并最终通过大量再吸收到静脉窦中或通过脉络丛主动转运到血液中连续去除。例如，脉络丛积极吸收神经递质血清素（即 5-羟基吲哚乙酸）和多巴胺（即高香草酸）的分解产物。
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
Glial cells constitute half the volume of the brain and outnumber neurons
5.2 星形胶质细胞以乳酸的形式为神经元提供燃料
Astrocytes supply fuel to neurons in the form of lactic acid
5.3 星形胶质细胞主要可渗透 K+，也有助于调节 [K+]o
Astrocytes are predominantly permeable to K+ and also help regulate [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
Gap junctions couple astrocytes to one another, allowing diffusion of small solutes
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
Astrocytes synthesize neurotransmitters, take them up from the extracellular space, and have neurotransmitter receptors
5.6 星形胶质细胞分泌营养因子，促进神经元存活和突触生成
Astrocytes secrete trophic factors that promote neuronal survival and synaptogenesis
Astrocytes, and other glial cell types, are a source of important trophic factors and cytokines, including brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), basic fibroblast growth factor (bFGF), and ciliary neurotrophic factor (CNTF). Moreover, both neurons and glial cells express receptors for these molecules, which are crucial for neuronal survival, function, and repair. The expression of these substances and their cognate receptors can vary during development and with injury to the nervous system.
星形胶质细胞和其他神经胶质细胞类型是重要营养因子和细胞因子的来源，包括脑源性神经营养因子 （BDNF）、神经胶质细胞源性神经营养因子 （GDNF）、碱性成纤维细胞生长因子 （bFGF） 和睫状神经营养因子 （CNTF）。此外，神经元和神经胶质细胞都表达这些分子的受体，这对神经元的生存、功能和修复至关重要。这些物质及其同源受体的表达在发育过程中和神经系统损伤过程中会发生变化。
The development of fully functional excitatory synapses in the brain requires the presence of astrocytes, which act at least in part by secreting proteins called thrombospondins. Indeed, synapses in the developing CNS do not form in substantial numbers before the appearance of astrocytes. In the absence of astrocytes, only ~20% of the normal number of synapses form.
大脑中功能齐全的兴奋性突触的发育需要星形胶质细胞的存在，星形胶质细胞至少部分是通过分泌称为血小板反应蛋白的蛋白质发挥作用的。事实上，在星形胶质细胞出现之前，发育中的 CNS 中的突触并没有大量形成。在没有星形胶质细胞的情况下，仅形成正常突触数量的 ~20%。
5.7 星形胶质细胞终足调节脑血流
Astrocytic endfeet modulate cerebral blood flow
Astrocytic endfeet (see p. 286) surround not only capillaries but also small arteries. Neuronal activity can lead to astrocytic [Ca2+]i waves—as previously described on pages 291– 292 that spread to the astrocytic endfeet, or to isolated increases in endfoot [Ca2+]i. In either case, the result is a rapid increase in blood vessel diameter and thus in local blood flow. A major mechanism of this vasodilation is the stimulation of phospholipase A2 in the astrocyte, the formation of arachidonic acid, and the liberation through cyclooxygenase 1 (see Fig. 3-11) of a potent vasodilator that acts on vascular smooth muscle. This is one mechanism of neuron-vascular coupling—a local increase in neuronal activity that leads to a local increase in blood flow. Radiologists exploit this physiological principle in a form of functional magnetic resonance imaging (fMRI) called blood oxygen level–dependent (BOLD) MRI, which uses blood flow as an index of neuronal activity.
星形胶质细胞终足（见第 286 页）不仅围绕毛细血管，还围绕小动脉。神经元活动可导致星形胶质细胞 [Ca2+]i 波——如前面第 291-292 页所述，扩散到星形胶质细胞末足，或导致末足 [Ca2+]i 的孤立增加。在任何一种情况下，结果都是血管直径迅速增加，从而增加局部血流量。这种血管舒张的一个主要机制是刺激星形胶质细胞中的磷脂酶 A2，形成花生四烯酸，以及通过环氧合酶 1（见图 3-11）释放作用于血管平滑肌的强效血管扩张剂。这是神经元-血管耦合的一种机制——神经元活动的局部增加导致血流的局部增加。放射科医生以一种称为血氧水平依赖性 （BOLD） MRI 的功能性磁共振成像 （fMRI） 形式利用这一生理原理，它使用血流作为神经元活动的指标。
Astrocytic modulation of blood flow is complex, and increases in [Ca2+]i in endfeet can sometimes lead to vasoconstriction.
星形胶质细胞对血流的调节很复杂，末端足中 [Ca2+]i 的增加有时会导致血管收缩。
5.8 少突胶质细胞和雪旺细胞制造并维持髓鞘
Oligodendrocytes and Schwann cells make and sustain myelin
5.9 少突胶质细胞参与大脑中的 pH 调节和铁代谢
Oligodendrocytes are involved in pH regulation and iron metabolism in the brain
Oligodendrocytes and myelin contain most of the enzyme carbonic anhydrase within the brain. The appearance of this enzyme during development closely parallels the maturation of these cells and the formation of myelin. Carbonic anhydrase rapidly catalyzes the reversible hydration of CO2 and may thus allow the CO2 /HCO3- buffer system to be maximally effective in dissipating pH gradients in the brain. The pH regulation in the brain is important because it influences neuronal excitability. The classic example of the brain’s sensitivity to pH is the reduced seizure threshold caused by the respiratory alkalosis secondary to hyperventilation (see p. 634).
少突胶质细胞和髓鞘含有大脑内的大部分碳酸酐酶。这种酶在发育过程中的出现与这些细胞的成熟和髓鞘的形成密切相关。碳酸酐酶可快速催化 CO2 的可逆水合，因此可能使 CO2 /HCO3- 缓冲系统在消散大脑中的 pH 梯度方面发挥最大作用。大脑中的 pH 调节很重要，因为它会影响神经元的兴奋性。大脑对 pH 值敏感的典型例子是由过度换气继发的呼吸性碱中毒引起的癫痫发作阈值降低（见第 634 页）。
Oligodendrocytes are the cells in the brain most involved with iron metabolism. They contain the iron storage protein ferritin and the iron transport protein transferrin. Iron is necessary as a cofactor for certain enzymes and may catalyze the formation of free radicals (see pp. 1238–1239) under pathological circumstances, such as disruption of blood flow to the brain.
少突胶质细胞是大脑中与铁代谢最相关的细胞。它们含有铁储存蛋白铁蛋白和铁转运蛋白转铁蛋白。铁作为某些酶的辅助因子是必需的，并且在病理情况下可能会催化自由基的形成（参见第 1238-1239 页），例如破坏流向大脑的血流。
Oligodendrocytes, like astrocytes, have a wide variety of neurotransmitter receptors. Unmyelinated axons can release glutamate when they conduct action potentials, and in principle, this glutamate could signal nearby oligodendrocytes. Ischemia readily injures oligodendrocytes, in part by releasing toxic levels of glutamate. Even white matter, therefore, can suffer excitotoxicity.
少突胶质细胞和星形胶质细胞一样，具有多种神经递质受体。无髓轴突在传导动作电位时可以释放谷氨酸，原则上，这种谷氨酸可以向附近的少突胶质细胞发出信号。缺血很容易损伤少突胶质细胞，部分原因是释放有毒水平的谷氨酸。因此，即使是白质也会遭受兴奋性毒性。
5.10 小胶质细胞是中枢神经系统的巨噬细胞
Microglial cells are the macrophages of the CNS
Microglial cells are of mesodermal origin and derive from cells related to the monocyte-macrophage lineage. Microglia represent ~20% of the total glial cells within the mature CNS. These cells are rapidly activated by injury to the brain, which causes them to proliferate, to change shape, and to become phagocytic (Fig. 11-15). When activated, they are capable of releasing substances that are toxic to neurons, including free radicals and nitric oxide. It is believed that microglia are involved in most brain diseases, not as initiators but as highly reactive cells that shape the brain’s response to any insult.
小胶质细胞起源于中胚层，来源于与单核细胞-巨噬细胞谱系相关的细胞。小胶质细胞占成熟 CNS 内神经胶质细胞总数的 ~20%。这些细胞因大脑损伤而迅速激活，导致它们增殖、改变形状并成为吞噬细胞（图 11-15）。当被激活时，它们能够释放对神经元有毒的物质，包括自由基和一氧化氮。据信，小胶质细胞与大多数脑部疾病有关，不是作为引发剂，而是作为高度反应性的细胞，塑造大脑对任何损伤的反应。
Microglia are also the most effective antigen-presenting cells within the brain. Activated T lymphocytes are able to breech the BBB and enter the brain. To become mediators of tissue-specific disease or to destroy an invading infectious agent, T lymphocytes must recognize specific antigenic targets. Such recognition is accomplished through the process of antigen presentation, which is a function of the microglia.
小胶质细胞也是大脑中最有效的抗原呈递细胞。活化的 T 淋巴细胞能够破坏 BBB 并进入大脑。为了成为组织特异性疾病的介质或破坏侵袭的感染因子，T 淋巴细胞必须识别特定的抗原靶标。这种识别是通过抗原呈递过程完成的，这是小胶质细胞的一个功能。
6 Reference
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- http://www.cochlea.eu/en/cochlea
- http://www.cochlea.eu/en/cochlea/cochlear-fluids
