Studies on Cerebrospinal Circulation by a New Method

Sachs, Ernest; Wilkins, H.C.; Sams, Crawford F.

doi:10.1001/archneurpsyc.1930.02220070133007

Cited by 19 publications

(6 citation statements)

References 15 publications

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“…Early experiments with direct observation of the movement of dye administered to the CSF of laminectomized dogs resulted in the conclusion that there is no directional CSF flow 62 . In the same publication, the authors conclude that the substances in the CSF spread by diffusion and that there is no evidence that pulse and respiration play a role in the movement of CSF (we must note that the method was not precise enough to adequately support the latter conclusions).…”

Section: The “Flow” Of Csfmentioning

confidence: 99%

Physiology of the Intrathecal Bolus: The Leptomeningeal Route for Macromolecule and Particle Delivery to CNS

2013

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Presently, there are no effective treatments for several diseases involving the CNS, which is protected by the blood-brain, blood-CSF and blood-arachnoid barriers. Traversing any of these barriers is difficult, especially for macromolecular drugs and particulates. However, there is significant experimental evidence that large molecules can be delivered to the CNS through the cerebro-spinal fluid (CSF). The flux of the interstitial fluid in the CNS parenchyma, as well as the macro flux of CSF in the leptomeningeal space, are believed to be generally opposite to the desirable direction of CNS-targeted drug delivery. On the other hand, the available data suggest that the layer of pia mater lining the CNS surface is not continuous, and the continuity of the leptomeningeal space (LMS) with the perivascular spaces penetrating into the parenchyma provides an unexplored avenue for drug transport deep into the brain via CSF. The published data generally do not support the view that macromolecule transport from the LMS to CNS is hindered by the interstitial and CSF fluxes. The data strongly suggest that leptomeningeal transport depends on the location and volume of the administered bolus and consists of four processes: (i) pulsation-assisted convectional transport of the solutes with CSF, (ii) active “pumping” of CSF into the periarterial spaces, (iii) solute transport from the latter to and within the parenchyma, and (iv) neuronal uptake and axonal transport. The final outcome will depend on the drug molecule behavior in each of these processes, which have not been studied systematically. The data available to date suggest that many macromolecules and nanoparticles can be delivered to CNS in biologically significant amounts (>1% of the administered dose); mechanistic investigation of macromolecule and particle behavior in CSF may result in a significantly more efficient leptomeningeal drug delivery than previously thought.

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Section: The “Flow” Of Csfmentioning

confidence: 99%

Physiology of the Intrathecal Bolus: The Leptomeningeal Route for Macromolecule and Particle Delivery to CNS

2013

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“…The strands of the arachnoid meshwork are probably the main factor producing the resistance to diffusion in the spinal subarachnoid space of the cat during life although a contribution may be made by anatomical straits in the system. Sachs et al (1930) conclude that in anaesthetized dogs 'the idea that there is a true circulation in cerebrospinal fluid is incorrect. Substances in the cerebrospinal fluid spread by diffusion, but this diffusion is influenced to a great extent by gravity.'…”

Section: Discussionmentioning

confidence: 94%

Circulation of cerebrospinal fluid in the spinal region of the cat

Grundy¹

1962

The Journal of Physiology

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If formation and absorption of the cerebrospinal fluid (c.s.f.) occur at different sites an intervening circulation of the fluid is obligatory, and such a circulation may appreciably modify the spread of drugs introduced into the c.s.f. Nevertheless, few controlled observations have been made on this subject. The problems involved, with particular reference to spinal anaesthesia in man, were described by Maxson (1938), who also studied the movements under various conditions of red ink in an artificial spinal fluid contained in a glass model. Sachs, Wilkins & Sams (1930) compared by direct observation the movements of a marker dye introduced at various sites into the spinal subarachnoid space of anaesthetized dogs with those occurring in a glass model.The general aim of the present investigations is to study the effects of bodily activity upon the c.s.f. circulation. In this paper the movements of a marker dye in the spinal subarachnoid space of the prone horizontal anaesthetized cat have been compared with those occurring in a glass model. The effects of tilting or shaking the animal have been studied and also the effect of picrotoxin convulsions. METHODSCats were anaesthetized by intraperitoneal injection of sodium pentobarbitone (Abbott Laboratories, 30-40 mg/kg). In each experiment a cannula of known length and volume was inserted into the dorsal spinal subarachnoid space at one of three sites. When the cannula was to be inserted at the sacral site the laminae of the three sacral vertebrae were resected and the underlying extradural fat removed. A nylon cannula (No. 1 'Portex', Portland Plastics) with two oppositely-placed holes close to its sealed tip, filled with Ringer-Locke solution and stoppered, was introduced and tied in place with its tip pointing cranially at the first sacral vertebral level. In experiments in which the cannula was to be inserted at the cervical site, after laminectomy the right eighth cervical dorsal nerve root was exposed for about 5 mm from the cord. A cannula, as before, was introduced via the nerve-root sheath and tied so that it lay transversely across the subarachnoid space. For insertion at the thoracic site, after laminectomy the cannula (No. 00 'Portex') was introduced via the right twelfth thoracic nerve-root sheath and fixed with its tip cranially directed at the eleventh thoracic vertebral level.

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“…In the human brain, Pascal’s principle predicts that the ventricular size will remain unchanged throughout life, explaining why the CSF pressure is uniform in the ventricular system and subarachnoid spaces (there is no flow, only diffusion) ( 9 , 10 ). Physiological or pathological conditions that alter CSF absorption may result in slight changes in the mean CSF intra-ventricular volume and pressure.…”

Section: Discussionmentioning

confidence: 99%

Progressive Cognitive Impairment Evolving to Dementia Parallels Parieto-Occipital and Temporal Enlargement in Idiopathic Chronic Hydrocephalus: A Retrospective Cohort Study

Missori

Currà

2015

Front. Neurol.

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Little is known regarding progressive enlargement of the ventricular system in symptomatic patients or asymptomatic subjects. Before eventual surgical treatment, we evaluated the clinical and radiological features of an extremely rare group of patients with idiopathic chronic hydrocephalus (ICH) and cognitive impairment evolving to dementia (n = 11), and an extremely rare group of asymptomatic or minimally symptomatic adults (AMSA) with ventricular enlargement (n = 10). We quantified changes over time in the ventricular frontal, occipital, and temporal horns by measuring the Evans’ index plus a parieto-occipital ratio and a temporal ratio, and their percentage of progression. Cerebral ventricles expanded over very long term in both demented patients with ICH and in AMSA. In AMSA, frontal enlargement predominated, whereas demented patients showed predominant parieto-occipital (p = 0.00) and temporal (p = 0.00) enlargement that progressed faster than in AMSA (p = 0.00). In ICH, progression of cognitive impairment parallels ventricular parieto-occipital and temporal horn enlargement. Limitations of this study are the retrospective nature, the non-uniform use of neuropsychological tests, the reduced sample size due to the extremely stringent enrollment criteria, the inability to determine the precise rate of progression.

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Studies on Cerebrospinal Circulation by a New Method

Cited by 19 publications

References 15 publications

Physiology of the Intrathecal Bolus: The Leptomeningeal Route for Macromolecule and Particle Delivery to CNS

Physiology of the Intrathecal Bolus: The Leptomeningeal Route for Macromolecule and Particle Delivery to CNS

Circulation of cerebrospinal fluid in the spinal region of the cat

Progressive Cognitive Impairment Evolving to Dementia Parallels Parieto-Occipital and Temporal Enlargement in Idiopathic Chronic Hydrocephalus: A Retrospective Cohort Study

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