Amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS), also known as 'Lou Gehrig's disease' (named after a baseball player who died from ALS in 1941) was initially described by Charcot in 1869. This neurological disease is manifested by degeneration of motor neurones located in cortex, brain stem and spinal cord. Clinically the ALS appears in the form of progressive paralysis and muscle atrophy. One of the important determinants of neuronal death in ALS is represented by deficient glutamate clearance, and as a...

Astroglia regulate synaptic transmission

Astroglia affect neuronal synaptic transmission in several ways. First, astrocytes modulate synaptic strength by controlling the concentration of neurotransmitter in the cleft via glial transporters. This is the case for most synapses that use amino acid neurotransmitters, such as glutamate, GABA, and monoamines, where astrocytes express specific transporters, depending on the synapse (see Chapter 5.7). Alternative mechanisms of affecting neurotransmitter concentration exist in central...

Human immunodeficiency virus HIV infection

Brain damage is a frequent outcome of acquired immunodeficiency syndrome (AIDS), the pathology manifesting in a form of HIV-encephalitis (HIVE). The latter progresses through cognitive impairments, psychomotor abnormalities, including ataxia, towards severe HIV-associated dementia (HAD). In addition to HAD, AIDS also produces HIV-related sensory neuropathies. The combined prevalence of HIV-associated dementia and sensory neuropathies can reach up to 50 per cent in all patients. Microglia and...

Astrocytes as cellular substrate of memory and consciousness

Glial Cells The Brain

Contemporary neuroscience regards neuronal networks, and neuronal networks only, as the substrate of memory and consciousness. More than that, current understanding, in essence, denies the existence of special cells or cellular groups which can be the residence of memory, consciousness and other high cognitive functions. At the same time, information processing in the neuronal networks relies entirely on a simple binary code, which might not necessarily offer sophistication sufficient enough to...

Nonmyelinating Schwann Cells

Amoeboid Microglia

4.1 Phylogeny of glia and evolutionary specificity of glial cells in human brain Glia appear early in phylogeny even primitive nervous systems of invertebrates such as annelids and leeches, crustacea and insects, and molluscs and cephalopods contain clearly identifiable glial cells, and their study has provided a significant contribution to our understanding of glial cell physiology. Most strikingly, however, the evolution of the CNS is associated with a remarkable increase in the number and...

Gliomas

Schwann Cells

Gliomas are tumours of the nervous system, which develop from glial cells in fact they account for the majority of primary brain neoplasias. Clinically, gliomas are classified according to their malignancy (the WHO classification) into four grades grade I covers benign tumours (e.g. pilocytic astrocytoma), groups II to IV are malignant neoplasias which differ in their aggressiveness the most violent is glioblastoma, which belongs to group IV. Histopathologically, the gliomas are divided into...

Astrocytes may exacerbate brain damage upon ischaemia

Schwann Cell

Astrocytes, however, may act not only as protectors of the brain in certain conditions (especially upon severe insults) astroglial cells may exacerbate the cell damage, contributing to several vicious circles triggered by the stroke. First of all, the astroglial involvement in controlling brain glutamate concentration is double edged. The ability of astrocytes to remove glutamate from the extracellular space leads to glutamate accumulation in their cytosol in very high concentrations (up to 10...

Schwann Cells Electrically Excitable

Glial Cells The Brain

There are two major classes of cells in the brain - neurones and glia (Figure 1.1). The fundamental difference between these lies in their electrical excitability -neurones are electrically excitable cells whereas glia represent nonexcitable neural cells. Neurones are able to respond to external stimulation by generation of a plasmalemmal 'all-or-none' action potential, capable of propagating through the neuronal network, although not all neurones generate action potentials. Glia are unable to...

Neuronalglial synapses

Direct synaptic contacts between neuronal terminals and both NG2-glia and astrocytes have been identified in hippocampus and cerebellum Figure 6.3 . Two types of neuronal-glial synapses, the excitatory glutamatergic synapses and the inhibitory GABAergic, formed by the terminals of pyramidal neurones and interneurones respectively, were recently detected in the hippocampus. These synapses have a typical morphology, revealed by electron microscopy the latter shows axon terminals, filled with...

General Pathophysiology of Glia

The focus of this book is the normal biology of glia. However, glial cells are involved in almost every type of brain pathology. This is particularly true for microglia, which function primarily in pathology. In this final section of the book, therefore, we introduce some of the important aspects of the role of glia in pathology. Insults to the nervous system trigger specific reactions of glial cells, generally known as a reactive gliosis, which include the reaction of astroglia reactive...

Parkinsons disease

Parkinson's disease PD leads to activation of microglia and reactive astrogliosis in the brain areas affected by the disease. In particular, a rather prominent gliosis is observed in the substantia nigra SN , which contains the cell bodies of neurones forming the nigrostriatal pathway. Importantly, the SN neurones are particularly vulnerable to attack by activated microglia this observation initiated the hypothesis of microglia-mediated neurodegeneration and cell death as instrumental for PD...

Recommended literature

Kettenmann H, Ransom BR 1985 Neuroglia. Oxford University Press, 1st edition. Kettenmann H, Ransom BR 2005 Neuroglia. Oxford University Press 2nd edition. First definition of glia as an integrative part of brain parenchyma Virchow R 1846 ber das granulierte Ansehen der Wandungen der Gehirnventrikel. Allg Z Psychiatrie 3, 242-250. Virchow R 1858 Die Cellularpathologie in ihrer Begr ndung auf physiologische and pathologische Gewebelehre. Verlag von August Hirschfeld, Berlin. Andriezen L 1893 The...

Info

List Ligand Gated Ion Receptor

General Overview of Signalling in the Nervous System 2.1 Intercellular signalling Wiring and volume modes of transmission The fundamental question in understanding brain function is 'How do cells in the nervous system communicate ' At the very dawn of experimental neuroscience two fundamentally different concepts were developed. The 'reticular' theory of Camillo Golgi postulated that the internal continuity of the brain cellular network works as a single global entity, while the...

Diabetic neuropathies

Diabetic neuropathies are the most frequent complications of diabetes mellitus, which affect 50 per cent of all patients. Clinically, the sensory neuropathies dominate motor weakness develops rather rarely. The primary cause of nerve damage is associated with blood glucose levels aggressive glycaemic control substantially reduces the prevalence of neuropathies. The primary target of the impaired glucose homeostasis is, however, debatable. Traditionally, the leading aetiological factor was...

Signalling between Schwann cells and peripheral nerves and nerve endings

The perisynaptic Schwann cells are intimately integrated into the majority of vertebrate neuromuscular junctions. The processes of perisynaptic Schwann cells are closely associated with nerve terminals and send finger-like extensions directly into the synaptic cleft where they terminate very closely to the active zones. Similar to astrocytes, perisynaptic Schwann cells utilize intracellular Ca2 as the substrate of their excitation. High-frequency stimulation of nerve terminals triggers Ca2 i...

Alzheimers disease

Stages Alzheimer Disease

Alzheimer's disease AD , together with multi-infarct dementia, is the main cause of senile dementia. AD, named after Alois Alzheimer, who was the first to describe this pathology in 1907, is characterized by profound neuronal loss throughout the brain which rapidly compromises memory and results in severe impairment of cognitive functions. Histological hallmarks of AD are represented by the formation of deposits of -amyloid protein A in the walls of blood vessels, accumulation of A plaques in...

Morphological plasticity of astroglial synaptic compartment

Regions Schwann Cell

Astrocytes are able to directly influence synaptic transmission in certain brain regions by changing their morphology and thus remodelling the structure of the Figure 7.13 Example of modulation of synaptic transmission by glia. Stimulation of astrocytes in astroglial neuronal co-cultures significantly reduces the amplitudes of glutamatergic excitatory postsynaptic potentials EPSPs in neighbouring neurones. Modified from Araque A, Parpura V, Sanzgiri RP Haydon PG 1998 Glutamate-dependent...

Composition of myelin

The main constituents of myelin are the lipids 70 per cent of its dry weight , the remainder being proteins 30 per cent of its dry weight , which are largely specific to myelin, with subtle differences between PNS and CNS Figure 8.7 . The lipids provide myelin with its insulating properties, whereas the proteins serve to fuse and stabilize myelin lamellae and to mediate membrane-membrane interactions between the myelin lamellae, and between the axon and myelin sheath. Our understanding of their...

Vanishing white matter disease

Vanishing white matter disease VWM is one of the most prevalent inherited childhood white-matter disorders. It was described in 1962 by Eicke. VWM is caused by mutations in any of the five genes encoding the subunits of eukaryotic translation initiation factor eIF2B, and is manifested by chronic progressive neurological deterioration with cerebellar ataxia and mild mental decline. The disease is usually revealed at an early age of two to six years, and most of the patients die within several...

Acquired inflammatory neuropathies

Acquired peripheral neuropathies are broadly classified into acute and chronic inflammatory demyelinating neuropathies AIDP and CIDP, respectively . Clinical forms of these neuropathies are many, and all of them proceed with sensory abnormalities or motor weaknesses, or a combination of both. Pathogenetically inflammatory neuropathies belong to autoimmune diseases the actual neuropathy usually follows viral infection the latter triggers an immune response, which turns into an autoimmune...

Psychiatric diseases 10101 Epilepsy

Pathogenesis Epilepsy Seizure

Epilepsy results from abnormal synchrony in the neuronal networks, when many nerve cells start to fire simultaneously. These discharges can be visualized on the EEG, which reveals cortical spikes and sharp waves. The cellular substrate of epilepsy is a slow depolarization of neurones, which occurs without any apparent provocation and develops synchronously in virtually all nerve cells within the epileptic foci. This slow neuronal depolarization is known as paroxysmal depolarization shift, PDS....

Neurogenesis in the adult brain

In many vertebrates, neurogenesis persists throughout adulthood throughout the CNS. For example, new neurones are continuously born in all brain regions in birds, whilst lizards can very effectively regenerate the retina and spinal cord. In primates, including humans, neurogenesis in the adult is restricted to the hippocampus and subventricular zone. In both locations, the stem elements that produce neurones are astroglia. These 'stem' astrocytes have the morphology, physiology and biochem-ical...

Myelin structure

Schwann Cells Longtudinal

The myelin sheath is wrapped around the axon to form concentric layers or lamellae, which are best seen in transverse section Figure 8.2 . Longitudinally along axons, consecutive myelin sheaths are separated by nodes of Ranvier, the highly specialized areas of naked axonal membrane where action potentials are propagated see Chapter 8.4 . The myelin sheath between nodes is therefore called Figure 8.2 The myelin sheath in transverse section. The myelin sheath is seen to be formed by multiple...

Astrocyte GABA transporters

The role of astroglial cells in GABA uptake is not very prominent, as the majority of GABA released during neurotransmission is accumulated by both pre- and postsynaptic neurones. Nonetheless, astrocytes do express GABA transporters, and their activity contributes to overall GABA uptake. All three types of GABA transporters, classified as GAT-1 to GAT-3, have been detected in astrocytes the expression of GAT-3 dominates in cortical and hippocampal astrocytes, whereas cerebellar Bergmann glial...

Oligodendrocytes Schwann Cells and Myelination

Schwann Cell

The function of oligodendrocytes is to produce the myelin sheaths that insulate axons in the CNS. Myelinating Schwann cells serve the same function in the PNS, but there are also significant populations of nonmyelinating and perisynaptic terminal Schwann cells Figure 8.1 . Myelinating and nonmyelinating Schwann cells are equally numerous. These multiple Schwann cell types perform many of the diverse functions performed by astrocytes in the CNS - such as structure, metabolism, regulation of the...

Oligodendrocytes and microglia in stroke

Death of oligodendrocytes leads to axonal disintegration as mentioned above oligodendroglia are particularly vulnerable to focal ischaemia. Strokes located in the white matter may therefore trigger particularly dangerous disruptions of nerve fibres and lead to severe functional disabilities such as focal insults in the internal capsule . Microglial cells are also activated during brain ischaemia their activation is associated with the release of numerous immunocompetent molecules, which can...

Astrocyte glycine transporters

Astroglial cells are heavily involved in transportation of glycine, which acts as a neurotransmitter inhibitory as well as excitatory in several regions of the nervous system, particularly in the spinal cord. In addition, glycine is an important neuromodulator acting on NMDA receptors throughout the brain. Glycine transporters present in neurones and astrocytes are functionally and structurally different. Astrocytes predominantly express Glycine transporter 1 GlyTl , while neurones express...

Nonvesicular release of neurotransmitter from astrocytes

Passage Neurotransmitter

Several types of neurotransmitters, including glutamate, ATP and aspartate, can be released from astrocytes through plasmalemmal routes, namely via reversed activity of neurotransmitter transporters or via plasmalemmal channels Figure 5.14 . Reversed activity of transporters can result in glutamate release from astrocytes and maybe also from oligodendrocytes this can happen in conditions of increased intracellular concentrations of Na or glutamate, combined with cell depolarization caused by an...

Astroglia protect the brain against ischaemia

Ascorbate Glutathione Cycle

Notwithstanding the detrimental effects of profound ischaemia on astroglial cells, the latter still remain the most resistant elements of neural circuits, which protect the brain against injury Figure 10.4 . First and foremost, astrocytes form the main barrier against glutamate excito-toxicity. Astroglial cells, by virtue of numerous transporters see Chapters 5.7 and 7.8 expressed in their membrane, act as the main sink for the glutamate in the CNS. Furthermore, the astroglial ability to...

Glial syncytium gap junctions

Structure Schwann Cell

Macroglial cells in the brain are physically connected, forming a functional cellular syncytium. This represents a fundamental difference between neuronal and glial networking. For the vast majority of neurones, networking is provided by synaptic contacts. The latter preclude physical continuity of the neuronal network, while providing for functional inter-neuronal signal propagation. In contrast, glial networks are supported by direct intercellular contacts, generally known as gap junctions....

Wallerian degeneration

Degeneration Peripheral Nerve

The severance of axon from the nerve body initiates a series of coordinated events, which produce the disintegration of distal axonal segments, removal of myelin and remodelling of myelinating cells, and finally nerve fibre regeneration, by axonal growth from the nerve slump proximal to the site of insult. This process of nerve degeneration was discovered by Augustus Waller in 1850 and is generally known as 'Wallerian degeneration'. The term Wallerian degeneration is currently used to describe...

Glutamate receptors

Glutamate Receptor Types

Glutamate is the main excitatory amino acid neurotransmitter in the brain, and glial cells, like neurones, express a wide variety of ionotropic and metabotropic glutamate receptors Figure 5.3 . Figure 5.3 Types of glutamate receptors two fundamentally different classes of glutamate receptors are represented by ionotropic receptors iGluR and seven-transmembrane-domain G-protein coupled metabotropic receptors mGluR . The iGluR are divided into three distinct subtypes, following the discovery of...

Activation of microglia

Microglial Activation

Microglia are the immunocompetent cells specifically equipped to monitor the CNS environment. They represent the endogenous brain defence and immune system, which is responsible for CNS protection against all types of pathogenic factors. Microglial cells are not neural cells by their origin see Chapter 3.5 , nonetheless after invading and setting down in the CNS, they acquired a very specific phenotype, which clearly distinguish them from their ancestors, the blood-derived macrophages. The most...

Regulation of brain microcirculation

Brain Microcirculation

Increase in brain activity is tightly linked to the circulation, and local stimulation of neurones triggers a rapid increase in local blood flow. This phenomenon, known as functional hyperaemia, was discovered by Sherrington in 1890. Functional hyperaemia is a local phenomenon as vasodilatation occurs in small vessels within 200-250 m from the site of increased neuronal activity. Mechanisms of functional hyperaemia remained enigmatic for a long time several hypotheses highlighted the role of...

Cytotoxic brain oedema

Swelling The Brain

Homeostatic regulation of brain volume and water content is of paramount importance for its function. Brain size is limited by the skull, and therefore even minute increases in brain volume lead to an increase in intracranial pressure and compression damage of neural tissue. Water redistribution between brain compartments compromises the extracellular space with similarly grave consequences. Brain oedema is in essence a collapse of brain volume water regulation, which exists in two forms -...

Electrical activity and myelination

Neural electrical activity has opposing effects on the development of oligoden-drocytes and Schwann cells. In the PNS, electrical activity inhibits myelination, by down-regulation of L1 and by the release of ATP to act on P2Y receptors on Schwann cells and inhibit their proliferation, differentiation and myelination. Electrical activity has the opposite effect in the CNS. Blocking tetrodotoxin or increasing alpha-scorpion toxin neuronal electrical activity respectively inhibit and promote...

Glial cell death during ischaemia

Glial Cells Location

The cells located within the infarction core region rapidly undergo an anoxic depolarization as a result neurones cease to be electrically excitable and lose their ability to maintain transmembrane ion gradients. This results in a considerable Na and Ca2 influx into the cells accompanied by a substantial K efflux, so that very Figure 10.1 Histology of focal ischaemic damage of the brain. The focal ischaemic damage or stroke comprises the central zone of the infarction core, where all the cells...

Intracellular transport of myelin components

The formation of the myelin sheath is a highly complex process that involves a number of steps, from mRNA transcription to protein translation and assembly into the membranes. All of the myelin products have to be transported from the cell body and targeted to the 'workface' of the myelin sheath, over hundreds and potentially thousands of microns via the connecting branches in oligodendrocytes , and along the outer cytoplasmic ridge, down the paranodal loops, into the inner cytoplasmic ridge...

Astrocyte glutamate transporters

Astrocyte Transporter

Removal of glutamate from the extracellular space is accomplished by specialized glutamate transporters expressed in both neurones and astroglial cells. Normal extracellular glutamate concentration varies between 2 and 5 M, reaching higher levels only for very brief moments at the peak of synaptic transmission. Intracellular glutamate concentration, in contrast, is much larger, being in the range of 1 to 10 mM. Therefore, removal of glutamate from the extracellular space requires transportation...

Cellular Ca2 regulation

Calcium Homeostasis Channel

The free intracellular Ca2 represents only a small 0.001 per cent fraction of total cellular calcium. Within the cells free Ca2 is very unevenly distributed between intracellular compartments. Cytosolic free Ca2 concentration Ca2 j is very low, being in the range of 50-100 nM. Calcium concentration within the ER is much higher, varying between 0.2 and 1.0 mM, and being therefore similar to extracellular Ca2 concentration, which lies around 1.5-2.0 mM Figure 5.10 . As a result of these...

Signalling from neurones to astrocytes

Schwann Cell

Stimulation of neurones or neuronal afferents triggers Ca2 signalling in astrocytes both in cell cultures and in situ in brain slices. Moreover, astroglial cells are able to distinguish the intensity of neuronal activity. Astroglial Ca2 oscillations induced by neuronal stimulation are clearly frequency encoded, the frequency increasing following an increase in synaptic activity. For example, it was found that astrocytes in hippocampus were able to follow the frequency of stimulation of neuronal...

Vesicular release of neurotransmitter from glial cells

Life Cycle Neurotransmitters

Vesicular release, also known as exocytosis, is the main pathway for regulated secretion of neurochemicals by neurones. Exocytosis underlies the very rapid Ca2 -dependent release of neurotransmitter in neuronal synapses as well as the much slower also Ca2 -dependent process of secretion of various neuro-modulators and neuro-hormones. An important feature of the exocytotic mechanism is that it is activated by local increases in intracellular Ca2 concentration the latter being produced either by...

Functional development of oligodendrocytes

During development, both oligodendrocytes and Schwann cells pass through a number of physiologically distinct stages that can be identified by the expression of stage-specific antigens and are characterized by marked changes in proliferation, migration, morphology and function. Oligodendrocyte progenitor cells OPCs develop in highly localized ventricular zones in the brain and spinal cord, by a process that depends on the transcription factors Oligl, Olig2, SOXIO and Nkx2.2, and the signalling...

Astrocytes and extracellular potassium homeostasis

Potassium Buffering

During intense but still physiological neuronal activity the extracellular potassium concentration may rise almost twice, from 2-2.5 mM to 4-4.2 mM such an increase can be observed, for example, in the cat spinal cord during rhythmic and repetitive flexion extension of the knee joint. As a rule, however, during regular physiological activity in the CNS the K o rarely increases by more than 0.2 to 0.4 mM. Nonetheless, locally, in tiny microdomains such as for instance occurring in narrow clefts...

Astrocytes and extracellular Ca2

Muller Cell

Calcium concentration in small extracellular compartments and particularly in perisynaptic compartments may fluctuate rather substantially, as Ca2 is accumulated by neurones when the invading action potential activates Ca2 channels. The actual Ca2 ocan decrease below 1 mM, which may affect generation of Ca2 signals in the terminal, and hence neurotransmission. The lowering of extracellular Ca2 concentration to 0.5 mM triggers Ca2 signalling in astrocytes, which originates from InsP3-driven...

Ion homeostasis in the extracellular space

Ion Pump Homeostasis

Maintenance of the extracellular ion composition is of paramount importance for brain function, because every shift in ion concentrations profoundly affects the membrane properties of nerve cells and hence their excitability. Brain extracellular space contains high amounts of Na Na o 130 mM and Cl- Cl- o 100 mM , whereas it is rather low in K K o 2-2.5 mM . This is reversed inside the brain cells, as the cytosol of most of neurones and glia is rich in K K - 100-140 mM and poor in Na Na - lt 10...

Redistribution of water following neuronal activity and regulation of the extracellular space

Astrocyte Channels

High synaptic activity is associated with a transient decrease in the extracellular space surrounding the active synapses. This is physiologically important, as local restriction of the extracellular space modulates the efficacy of synaptic transmission by 1 increasing the local concentration of neurotransmitter, and 2 limiting the spillover of the transmitter from the synaptic cleft. This local shrinkage of the extracellular space following neuronal activity is regulated by water transport...

Regulation of synaptogenesis and control of synaptic maintenance and elimination

The living brain constantly remodels and modifies its cellular networks. Throughout life, synapses continuously appear, strengthen, weaken or die. These processes underlie the adaptation of the brain to the constantly changing external environment and, in particular, represent what we know as learning and memory. For many years the process of synaptogenesis, maintenance and elimination of the synaptic contacts was considered to be solely neuronal responsibility only very recently it has become...

CNS myelin

Myelin Sheath Pns Composition

Lipids Cholesterol is a major component of myelin, together with phospholipids and glycolipids, in ratios ranging from 4 3 2 to 4 4 2. Myelin phospholipids are not unusual, but myelin lipids are rich in glycosphingolipids, in particular galactocerebrosides GalC and their sulphated derivatives, sulphatides, which are used immunohistochemically to identify myelinating oligodendrocytes. The functions of GalC have been studied in mice with an inactive gene for the enzyme that catalyzes the final...

PNS myelin

The specific galactolipids found in PNS myelin are largely the same as CNS myelin, although some glycolipids such as sulphated glucoronyl paragloboside and its derivatives are specific for PNS myelin. The major CNS myelin proteins are also found in PNS myelin, and the main ones that are special to PNS myelin are peripheral myelin protein zero P0 , peripheral myelin protein 22 PMP22 , peripheral nerve P2 protein, and periaxin. P0 is a glycoprotein and a member of the IgCAM superfamily. It...

Glial cells produce and release neuropeptides

All types of glial cells produce and release neuropeptides Table 5.4 . The production of neuropeptides is highly region specific, and in many cases developmentally regulated. In particular, astroglial cells synthesize many types of opioid peptides such as enkephalins, which are involved in the regulation of cell proliferation and dendritic growth in the CNS. Similarly, opioids proenkephalin and prodynorphin are expressed in cells of the oligodendrocyte lineage, and may be involved in regulation...

Organization of nodes of Ranvier

Saltatory Conduction Myelinated

The myelin sheath, produced by oligodendrocytes and Schwann cells, divides the axon into myelinated internodal segments, the length of which may vary between 100 m for small axons to 1 mm for large-diameter fibres. The internodal segments are separated by nonmyelinated regions, known as nodes of Ranvier Figure 8.10 . The myelin, being a perfect isolator, therefore divides the membrane Figure 8.10 The node of Ranvier. Saltatory conduction, whereby action potentials jump from node to node, is...

Axonglial interactions and the control of myelination

Shwaan Cells

The ensheathment and myelination of axons during development proceeds in a series of steps that requires complex and reciprocal interactions between axons and the myelinating cells Figure 8.8 . In the first phase, oligodendrocytes and Schwann cells have to recognize axons that require myelination. In a second phase, the processes of the premyelinating cell must adhere to the axons and begin to ensheath them. In a third phase, axons and the myelinating cells pass through a series of...

Myelin and propagation of the action potential

Creation of the myelin sheath was an extremely important evolutionary step, which dramatically boosted the velocity of nerve impulse propagation, which was critically important for increase in the animal size. The speed of conduction of a given axon is directly and strictly dependent on axon diameter, whereby larger axons conduct faster than smaller diameter axons Figure 8.9 this is a function of the relationship between the low resistance of the axoplasm and the high resistance and capacitance...

Structural function creation of the functional microarchitecture of the brain

Protoplasmic Astrocyte

Protoplasmic astrocytes in the grey matter are organized in a very particular way, with each astrocyte controlling its own three-dimensional anatomical territory Figure 7.3 . The overlap between territories of neighbouring astroglial cells is minimal and it does not exceed five per cent, i.e. astrocytes contact each other only by the most distal processes. Individual astrocytes establish contacts with blood vessels, neurones and synapses residing within their anatomical domain. Astrocytic...

Vascular function creation of glialvascular interface bloodbrain barrier and glianeuronevascular units

Brain Capillary Peripheral Capillary

The brain tissue is separated from blood by three barrier systems 1 the choroid plexus blood-CSF barrier in the ventricles of the brain, formed by tight junctions between the choroid plexus epithelial cells, which also produce the CSF 2 the arachnoid blood-CSF barrier separating the subarachnoid CSF from the blood and formed by tight junctions between the cells of the arachnoid mater surrounding the brain and 3 the blood-brain barrier between the intracerebral blood vessels and the brain...

Developmental function neuronal guidance

Glial Cell Migration

The vertebrate brain develops from the embryonic neuroectoderm that lies above the notochord and gives rise to the entire nervous system. The notochord induces neuroectodermal cells to generate neural stem cells and form the neural plate, which in turn forms the neural tube, from which the brain and spinal cord are derived. The neural precursor cells of the neural tube give rise to both neurones and glia in response to multiple inductive signals produced by the notochord, floor plate, roof...

Neuronal metabolic support

Glycolysis Lactate Astrocyte

The brain produces energy by oxidizing glucose the brain receives glucose and O2 from the blood supply. Glucose is transported across the blood-brain barrier via glucose transporter type 1 GLUT1 , which is specifically expressed in endothe-lial cells forming the capillary walls. Following transport across the blood-brain barrier, glucose is released into the extracellular space and is accumulated by neural cells via more plasmalemmal glucose transporters Figure 7.12 neurones predominantly...

Close apposition of neurones and astroglia the tripartite synapse

Tripartite Synapse

In the grey matter, astrocytes are closely associated with neuronal membranes and specifically with synaptic regions, so that in many cases astroglial membranes completely or partially enwrap presynaptic terminals as well as postsynaptic structures. In the hippocampus, for example, 60 per cent of all axon-dendritic synapses are surrounded by astroglial membranes. These astrocyte-synapse contacts show peculiar specificity astroglial membranes enwrap about 80 per cent of large perforated synapses...

Gliogenesis in adult brain

Gliogenesis

In the adult brain, in contrast to neurogenesis, gliogenesis occurs everywhere. New glial cells are born locally and the locality also mainly determines the type of glial cell produced. In the subcortical white matter most of the newly produced glial cells are oligodendrocytes, whereas in the spinal cord astrocytes and oligodendrocytes are produced roughly in the same quantities. Figure 7.1 Astrocytes as stem elements in the nervous system. In the adult CNS, 'stem' astrocytes can produce both...

Reactive astrogliosis

Astroglia Damage

All types of brain insults, regardless of aetiology, trigger a complex astroglial response, which is manifested by astrocyte hypertrophy and proliferation. This glial response is defined as reactive astrogliosis Figure 9.1 . Reactive astrogliosis is a defensive brain reaction which is aimed at a isolation of the damaged area from the rest of the CNS tissue, b reconstruction of the blood-brain barrier, and c facilitation of the remodelling of brain circuits in areas surrounding the lesioned...

Purinoreceptors

Schwann Cells And Receptors

The broad class of purinoreceptors are represented by molecules sensing various purinergic nucleotides, which are commonly present in the brain interstitium. These purinergic nucleotides, represented by adenosine triphosphate, adenosine and their metabolites, are released from both neurones and glial cells in several ways. Generally, purinoreceptors are divided into adenosine A receptors and ATP or P2 receptors of the P2X ionotropic and P2Y metabotropic subtypes Figure 5.4 . All glial cell...

Signalling from astrocytes to neurones

Astrocyte Closes Synapse

Calcium signals, which occur in astroglial cells either spontaneously or in response to activation of neighbouring neurones, are capable of triggering the release of neurotransmitters from the glial cells see Chapter 5.6 . It is now firmly established that these 'glio' transmitters can directly affect the neurones residing in the vicinity of the glial cells. This glial to neurone signalling is mediated by either ionotropic or metabotropic receptors present in the neuronal membrane. In...

Cytokine and chemokine receptors

Schwann Cells Ctokines

All types of glial cells express various combinations of cytokine and chemokine receptors, which in general control their proliferation, growth and metabolism. These receptors are involved in numerous pathological reactions of glial cells. The cytokine receptors are represented by two types, type I and type II receptors, which are activated by interferons and interleukins IL-2, 4, 6, 10, 12, 15 and 21 . The signalling pathways triggered by activation of these receptors involve the Janus kinases...