The blood—brain barrier and the extracellular space of brain

Davson, Hugh; Spaziani, Eugene

doi:10.1113/jphysiol.1959.sp006330

Cited by 156 publications

(59 citation statements)

References 13 publications

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“…This is partly the result of the very slow turnover of brain extracellular¯uid, which drains into the CSF (Cserr et al, 1981;Szentesvanyi et al, 1984), but is also related to the rate of bulk¯ow of the CSF out of the ventricles (Collins & Dedrick, 1983). Thus the CSF acts as a sink to the brain rather than the brain acting as a sink to the CSF (Davson et al, 1961).…”

Section: Discussionmentioning

confidence: 99%

“…The CSF bathes the exterior surfaces of the brain and ®lls the ventricles. Although exchange between brain and CSF is relatively unrestricted, the sink action of the CSF to the brain tissue prevents the CSF and brain interstitial uid from being in dynamic equilibrium (Davson et al, 1961;Cserr et al, 1981;Szentesvanyi et al, 1984). Overall, it would justi®ably appear that the blood-CSF barrier has the same functional goals as the BBB, with regard to protection and homeostasis, however the actual behaviour and ultrastructure of the choroid plexuses are quite di erent from that of the cerebral capillaries.…”

Section: Introductionmentioning

confidence: 99%

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The transport of the anti‐HIV drug, 2′,3′‐didehydro‐3′‐deoxythymidine (D4T), across the blood‐brain and blood‐cerebrospinal fluid barriers

Thomas

Segal

1998

British J Pharmacology

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1 The brain is a site of infection, viral replication and sanctuary for HIV-1. The treatment of HIV-1 infection therefore requires that an e ective agent be delivered to the brain. 2',3'-Didehydro-3'-deoxythymidine (D4T) is a nucleoside analogue which has been shown to have bene®cial clinical e ects in the treatment of HIV infection. However, although D4T has been detected in human CSF, the ability of this drug to cross both the blood-brain and blood-cerebrospinal¯uid (CSF) barriers and gain entrance into the brain tissue is not known. 2 This study examined the CNS entry of D4T by means of the bilateral vascular brain perfusion technique in the anaesthetized guinea-pig. 3 The results indicated that [ 3 H]-D4T had a limited ability to cross the blood-brain barrier (BBB), which was not signi®cantly greater than D-[ 14 C]-mannitol (a slowly penetrating marker molecule). Although D4T was found to cross the blood-CSF barrier, the presence of D4T in the CSF did not re¯ect levels of the drug in the brain tissue. 4 These results can be related to the measured low lipophilicity of D4T, the higher paracellular permeability characteristics of the choroid plexus (blood-CSF barrier) compared to the BBB, and the sink action nature of the CSF to the brain tissue. 5 In conclusion, these animal studies suggest that D4T may only penetrate the brain tissue to a limited extent and consideration should be given to these ®ndings in the clinical situation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The transport of the anti‐HIV drug, 2′,3′‐didehydro‐3′‐deoxythymidine (D4T), across the blood‐brain and blood‐cerebrospinal fluid barriers

Thomas

Segal

1998

British J Pharmacology

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“…the volume of effective flow each minute equals the volume of distribution of the solute. In the case of 1311-, distribution in muscle tissue has been variously reported from 20 % (Davson & Spaziani, 1959) to about 37-9 % of the total mass (Wallace & Brodie, 1937); the ratios listed in Table 2 are equivalent to distribution spaces of 26, 33, 45, and 49 %. The agreement with directly measured space is at least suggestive.…”

Section: Discussionmentioning

confidence: 99%

Evidence for the shift of blood to the nutritive circulation during reactive hyperaemia

Ballard¹,

Fielding²,

Hyman³

1964

The Journal of Physiology

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“…Equilibration of 36Cl and 22Na into brain is slow, 24 hr, compared with its equilibration into interstitial and connective tissue (25,26). The concentration of C1 and Na in CSF differ from ClE and NaE so that some active transport process must be postulated (27,28 (3,(6)(7)(8)(9)(10)(11).…”

Section: Discussionmentioning

confidence: 99%

Factors that limit brain volume changes in response to acute and sustained hyper- and hyponatremia

Holliday¹,

Kalayci²,

Harrah³

1968

J. Clin. Invest.

130

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A B S T R A C T Rats were made acutely hyper-or hyponatremic by infusion of hypertonic saline or water, respectively. Other rats were maintained in these states from 1 to 7 days to observe the effects of time. Brain tissue water, Na, Cl, and K were compared with serum Na and Cl concentration (NaE and ClE). The following observations are noted: Brain Cl content varies directly with CIE and brain Na content in the Cl space (Nae) varies directly with NaE, indicating little or no restraint on the inward or outward movement of Na or Cl from the Cl space of brain. The intracellular volume of brain fluid (Vi) derived as the difference between total water and Cl space, decreases with hypernatremia and increases with hyponatremia. The changes in V, in the acute studies are not accompanied by any change in brain K content, or calculated intracellular Na content, and are approximately 0.6 the changes predicted from osmotic behavior of cells, which apply four assumptions: (a) NaE is proportional to osmolality; (b) Experimental studies (3, 6-1 1) have documented the changes in brain fluid and electrolyte that occur with changes in osmolality that were specific for each study. The results have usually shown a change in brain Cl and Na content in the direction of the change in concentration of C1 and Na induced in plasma. Changes in K content in the brain have been noted in some experiments (6-9) but not in others (3,10,11). Except for the early study by Yannet (6), there has been little effort to generalize a quantitative relation between changes in plasma osmolality to changes in brain tissue water and electrolytes.The effects of changes in plasma osmolality upon brain fluid and electrolyte depend upon the rate with which brain water equilibrates with plasma water when a gradient in water potential develops, and the degree to which brain solute content is altered, since the latter influences the final distribution of water. Because rates of exchange for water and solute vary, time is an important element in characterizing changes in brainfluid volume. This is evident in clinical experience: hypertonic urea injections decrease brain volume, because urea diffusion into brain water is relatively slow and osmotic redistribution of water continues until urea equilibrium is reestablished; rapid reduction of plasma urea concentration in uremia by hemodialysis leads to transitory signs of brain swelling (12) for the same reason. It is also evident that those patients who develop hyponatremia slowly have fewer symptoms of central nervous system dysfunction than do those who develop it rapidly (13, 14).The studies reported here are designed to compare the effects of acute changes in plasma osmolality with those of sustained changes upon the Na and Cl content of the brain, the fluid phases of the brain, the K content, and the ratio of cation to water in brain fluid. In particular, we have compared the effects of changing osmolality upon observed cell volume with that predicted from the assumption that cell volume is a reciprocal func...

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The blood—brain barrier and the extracellular space of brain

Cited by 156 publications

References 13 publications

The transport of the anti‐HIV drug, 2′,3′‐didehydro‐3′‐deoxythymidine (D4T), across the blood‐brain and blood‐cerebrospinal fluid barriers

The transport of the anti‐HIV drug, 2′,3′‐didehydro‐3′‐deoxythymidine (D4T), across the blood‐brain and blood‐cerebrospinal fluid barriers

Evidence for the shift of blood to the nutritive circulation during reactive hyperaemia

Factors that limit brain volume changes in response to acute and sustained hyper- and hyponatremia

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