摘要:

SummaryThe advances in the knowledge of the histology of the central nervous system which have been made possible by improved staining techniques have complicated and confused the anatomical conception of the perivascular and perineuronal spaces. As a first step towards the resolution of this confusion, a clear picture must be formed of the elements which intervene between the tunica media of the cerebral and spinal blood vessels and the neurons.The blood vessels in the central nervous system possess little or no adventitial coat, and this element is replaced by a reticular perivascular sheath continuous with the pia‐arachnoid envelope of the brain and spinal cord. The question as to whether this reticular sheath extends to cover the capillaries remains to some extent unanswered, though the probability is that it does not do so. No clearly defined tissue layer serves to separate the outer wall of the reticular perivascular sheath from the neuron and its processes. In fixed preparations a felted network, formed by the perivascular feet of the neuroglia, which resembles a membrane, is seen, but we do not accept the view that this structure is part of the normal anatomy of the central nervous system. There remains an element on which little stress has previously been laid: this is the ground substance of the central nervous system, a tissue which is probably a muco‐polysaccharide in constitution, and which by virtue of its physical and chemical properties may well be of considerable importance in relation to the physiology of the central nervous system.The views of the earlier authorities on the anatomy of the perivascular and perineuronal spaces are difficult to reconcile with modern knowledge of the histology of the tissues concerned, and are of interest chiefly because of the influence which they have had on descriptions of these structures which are still accepted to‐day. After the first description of the perivascular space by Pestalozzi, important landmarks in the subsequent history of the spaces were: the adoption of the term ‘Virchow‐Robin space’ for the perivascular space; the description by His of a second space external to this; the discovery by Obersteiner that the perineuronal spaces were continuous with the space of His, and the confusion by later workers of the space of His with that of Virchow‐Robin, so that the perineuronal spaces were described as communicating through a perivascular canalicular system with the subarachnoid space.The most influential figure in moulding the modern conception of the perivascular and perineuronal spaces has been Weed. It appears that he accepted the notion, prevailing at the time at which his researches were carried out, of a complete canalicular system of spaces opening into the subarachnoid space; and it was unfortunate that the limitations of his Prussian blue technique were such as to lead him to support this misconception.Schaltenbrand&Bailey and Patek did much to resolve the confusion produced by the existence of the two systems of spaces, the true perivascular space of Virchow‐Robin and the artifact space of His or Held. Schaltenbrand&Bailey regarded the combined outer wall of the reticular perivascular sheath and glial membrane (their ‘Piaglialmembran’) as separating the two systems of spaces. Patek, who used an improved version of Wee?s technique, described one true perivascular space, the Virchow‐Robin space, with which the perineuronal spaces did not communicate, and three artifact spaces, with one of which, that between the glial membrane and the brain substance, the perineuronal spaces were in communication.The consideration of the views of previous workers, taken in conjunction with our own observations, leads us to believe that there are two systems of perivascular spaces: (1) the true perivascular spaces bounded by the layers of the reticular perivascular sheath; and (2) a great system of artifact spaces produced by shrinkage in the preparation of histological material and extending from the perineuronal spaces through the artifact perivascular spaces to the epispinal spaces of His.Such a conception of the histology of the perivascular and perineuronal spaces must, if accepted, alter some modern views on certain problems in connexion with the anatomy and physiology of the central nervous system. We suggest that the perivascular spaces serve neither for the production nor the absorption of the cerebro‐spinal fluid, but, being channels in which there is no established flow in one direction, act as cushions between the expansile vessels and the nerve cells. We also believe that our investigations show that the anatomical arrangements are such that the perivascular channels can play no significant part in the metabolism of the neuron.Whilst the perivascular and perineuronal spaces have in all probability little relevance to the problems of the blood‐brain barrier and the anatomy of the synapse, it is evident that the importance of the ground substance in relation to these problems has not be

ISSN:1464-7931    

DOI:10.1111/j.1469-185X.1954.tb00597.x

出版商:Blackwell Publishing Ltd    

年代:1954

数据来源: WILEY

摘要:

Summary1. Senescence is treated as a generic term for the processes in certain organisms which lead to a decreasing power of homoeostasis with increasing age.2. The presence of these processes in a species can be inferred from life‐tables prepared and interpreted with suitable precautions. It cannot be inferred from the desultory examination of anatomical changes in species of unknown life cycle. Secondary criteria of senescence, e.g. decline of reproductive capacity are of value in judging the degree of age change in individuals of well‐studied species.3. Decreasing homoeostasis with increasing age is known to arise from different causes in different phyla. No single general or ‘inherent’ process can be invoked to explain all types of senescence.4. Senescence occurs only rarely in the wild state, and except in large or social animals regularly occurring senescence is a feature of domestication.5. Susceptibility to senescence is apparently not universal in Metazoa, and may not be so in vertebrates. Probable exceptions to its occurrence are among forms where somatic cells are continually replaced, where there is no limiting size, or where virtual attainment of a limiting size is accompanied by a persisting capacity for growth.6. The ‘senescence’ of asexually reproducing protozoan stocks is not a phenomenon directly analogous to metazoan senescence.7. The specific age of invertebrates and of mammals can be modified by factors modifying the rate of development. The evidence in mammals indicates that senescence results from the attainment of a developmental stage, or from the exhaustion of developmental ‘programme’ not from the cessation of growthper se.8. The specific age varies widely between inbred stocks. Longevity is most readily produced by heterosis, and is probably a correlate of heterozygosity.9. The role of postponed lethal genetic effects, and of the reduction of the selection value of the individual with increasing age, in the evolution of senescence is discussed.The materials for this article were collected during the tenure of a personal grant from the Nuffield Foundation for study and research on the biology of senescence. I am also very grateful to many colleagues who have furnished me with facts and criticisms, without bearing any responsibility for the uses to which I have put them, and to Miss Rosemary Birbeck, for her work in preparing

ISSN:1464-7931    

DOI:10.1111/j.1469-185X.1954.tb00598.x

出版商:Blackwell Publishing Ltd    

年代:1954

数据来源: WILEY

摘要:

Summary1. The half‐century of investigations directed towards an understanding of the mechanism of β‐oxidation of fatty acids may be divided into three periods: (a) from 1904 to 1939 when the oxidation could be studied at the level of the intact animal or isolated organ or tissue slice; (b) from 1939 to 1952 when it could be studied at the mitochondrial level; and (c) from 1952 onwards when it could be reconstructed in non‐mitochondrial and soluble enzyme systems.2. The Knoop‐Dakin theory of β‐oxidation could not be directly confirmed owing to the non‐accumulation of any intermediates. The theory was based on deductions from the nature of the end‐products of the metabolism of phenyl fatty acids.3. The study of fatty acid oxidation at the mitochondrial level led to the recognition that the fatty acids are not oxidized as such but only in the form of some derivative whose formation is tied up with oxidative phosphorylation and the production of adenosine triphosphate (ATP).4. The transition from the mitochondrial system to soluble enzymes was facilitated first by the discovery that coenzyme A (CoA) was concerned in acyl transfer reactions and later by the recognition that the active fatty acids are indeed the fatty acyl derivatives of CoA.5. There are four known enzymatic processes by which fatty acyl CoA's are formed: (a) oxidation of pyruvate to acetyl CoA; (b) conversion of fatty acids to fatty acyl CoA's by ATP; (c) replacement of the succinyl group of succinyl CoA by short‐chain fatty acids; and (d) cleavage of β‐ketoacyl CoA's by CoA with formation of a fatty acyl CoA and acetyl CoA.6. Two separate enzymes are known to catalyse the oxidation of fatty acyl CoA's to their correspondingtransα, β‐unsaturated derivatives. The first is a green dehydrogenase containing copper and flavin as prosthetic groups which is active upon acyl CoA's from C3to C8. The metal is essential for the interaction of this dehydrogenase with cytochromec. The second is a yellow flavoprotein which is active upon acyl CoA's from C4to C18.7. Unsaturated fatty acyl CoA hydrase catalyses the hydration oftransα, β‐ or β, γ‐unsaturated CoA's to their correspondingl(+)‐β‐hydroxyacyl CoA derivatives. The enzyme acts upon all unsaturated derivatives from C4to at least C12. At equilibrium (pH 9, 250) the ratio β‐hydroxyacyl CoA:total unsaturated acyl CoA is 1. 4:1.8. The β‐hydroxyacyl CoA dehydrogenase catalyses the oxidation ofl(+)‐β‐hydroxyacyl CoA by DPN+. The product of oxidation is the corresponding β‐ketoacyl CoA. The enzyme is active over the entire range of fatty acid chain length. The E0of the reaction couple at pH 7.0 and 220is – 0.224 V. The equilibrium point of the oxidation is strongly pH dependent.9. The β‐ketoacyl CoA cleavage enzyme catalyses the reversible cleavage of β‐ketoacyl CoA's by another molecule of CoA to form acetyl CoA and a new acyl CoA with two carbon atoms less than the parent β‐ketoacyl CoA.10. The new fatty acyl CoA generated in the cleavage reaction undergoes a repeat cycle of β‐oxidation while the C2unit (acetyl CoA) undergoes condensation with oxalacetate to form citrate.11. Each of the component reactions in the β‐oxidation cycle has been shown to be reversible.12. The asymmetric labelling of acetoacetate formed during oxidation of labelled fatty acids by liver homogenates or mitochondrial suspensions is a phenomenon which can readily be explained in terms of the mechanism of the β‐ketoacyl CoA cleavage enzyme.13. The factors which militate against the accumulation of intermediates during fatty acid oxidation are discussed.14. The accumulation of acetoacetate in any tissue requires a combination of two essential conditions: (a) presence of acyl CoA deacylase; and (b) absence of a β‐ketoacid activation enzyme.15. Assuming that in the diabetic the operation of the citric acid cycle is subnormal by virtue of reduced conversion of glucose to pyruvate, it is possible to explain the accumulation of ketone bodies and its abolition by insulin in terms of the known enzyme reactions of the β‐oxidation cycle.16. The predominance of C16and C18fatty acids in lipids may be due to the fact that only the acyl CoA's of these particular acids dissociate to a sufficient degree from combination with the enzymes of the fatty acid oxidizing system as to become available for ester synthesis.It is a great pleasure to acknowledge my indebtedness to Dr Helmut Beinert for his advice and assistance in the preparation of the manuscrip

ISSN:1464-7931    

DOI:10.1111/j.1469-185X.1954.tb00599.x

出版商:Blackwell Publishing Ltd    

年代:1954

数据来源: WILEY