Extracellular space parameters in the rat neocortex and subcortical white matter during postnatal development determined by diffusion analysis

Lehmenkühler, A.; Syková, Eva; Svoboda, J.; Zilles, Karl; Nicholson, Charles

doi:10.1016/0306-4522(93)90503-8

Cited by 273 publications

(236 citation statements)

References 46 publications

Supporting

Mentioning

212

Contrasting

Order By: Relevance

“…Notably, the extracellular volume fraction is highest in the newborn and diminishes with age (20). The developmental analysis clearly showed that water resorption was delayed in the conditional animals compared with WT controls.…”

Section: Discussionmentioning

confidence: 94%

“…The developmental analysis clearly showed that water resorption was delayed in the conditional animals compared with WT controls. Interestingly, brain AQP4 expression becomes evident in the second postnatal week (21), at the time when there is a dramatic reduction in extracellular volume fraction (20). The differences in baseline water contents between glial-conditional knockout animals and controls were reproduced in specimens consisting of isolated hemispheres or caudal brainstem.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Glial-conditional deletion of aquaporin-4 ( Aqp4 ) reduces blood–brain water uptake and confers barrier function on perivascular astrocyte endfeet

Haj-Yasein

Vindedal

Eilert-Olsen

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

287

264

View full text Add to dashboard Cite

Tissue-and cell-specific deletion of the Aqp4 gene is required to differentiate between the numerous pools of aquaporin-4 (AQP4) water channels. A glial-conditional Aqp4 knockout mouse line was generated to resolve whether astroglial AQP4 controls water exchange across the blood-brain interface. The conditional knockout was driven by the glial fibrillary acidic protein promoter. Brains from conditional Aqp4 knockouts were devoid of AQP4 as assessed by Western blots, ruling out the presence of a significant endothelial pool of AQP4. In agreement, immunofluorescence analysis of cryostate sections and quantitative immunogold analysis of ultrathin sections revealed no AQP4 signals in capillary endothelia. Compared with litter controls, glial-conditional Aqp4 knockout mice showed a 31% reduction in brain water uptake after systemic hypoosmotic stress and a delayed postnatal resorption of brain water. Deletion of astroglial Aqp4 did not affect the barrier function to macromolecules. Our data suggest that the blood-brain barrier (BBB) is more complex than anticipated. Notably, under certain conditions, the astrocyte covering of brain microvessels is rate limiting to water movement. edema | electron microscopy | homeostasis | membrane | swelling M ore than 100 y have elapsed since it was first shown that some solutes present in blood are retained by brain capillaries, pointing to the existence of a barrier function at the bloodbrain interface. This early finding naturally inspired a discussion as to what could constitute the morphological substrate of this barrier (1). With the advent of the electron microscope it became clear that the blood-brain interface is composed of endothelia and pericytes, surrounded by a basal lamina and perivascular endfeet of astrocytes. After decades of intense debate, a concept emerged that the functional barrier resides at the level of the endothelial cells (2). This was consistent with morphological data, which clearly showed that endothelia were continuous and coupled by tight junctions (3). The perivascular endfeet, on the other hand, were not coupled by tight junctions and were portrayed as a discontinuous layer with spacious clefts separating the individual processes.Discussions on the morphological substrate of barrier function have been focused on solutes (4), and the field has not yet matured to provide a consistent view regarding what cellular structures, if any, restrict water movement between blood and brain. Following the discovery of water channels, it became clear that the major brain water channel AQP4 is implicated in water transport at the blood-brain interface. Thus, global Aqp4 knockout significantly limited the development of brain edema, attesting to the importance of AQP4 water channels (4). As AQP4 is strongly expressed in the perivascular endfeet (5), the interest in these processes was rekindled also in the context of their possible barrier function.Specifically, it was proposed that the endfeet could restrict water flow, most significantly in pathophysiological se...

show abstract

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Glial-conditional deletion of aquaporin-4 ( Aqp4 ) reduces blood–brain water uptake and confers barrier function on perivascular astrocyte endfeet

Haj-Yasein

Vindedal

Eilert-Olsen

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

287

264

View full text Add to dashboard Cite

show abstract

“…Each of the parameters ex, �, and k' within the dorsal hom gray matter remained the same in various layers (see also Svoboda and Sykova, 1991). The ex values were, however, significantly different in various cortical layers (Lehmenkiihler et al, 1993); e.g., in layers II and III, the mean ex values were 0.19 and 0.20, re spectively, while in layers V and VI, the mean ex values were 0.22 and 0.23. In striatal slices ex was 0.21 (range 0.18-0.24) (Rice and Nicholson, 1991).…”

Section: Diffusion Parameters During Normoxiamentioning

confidence: 87%

Extracellular Volume Fraction and Diffusion Characteristics during Progressive Ischemia and Terminal Anoxia in the Spinal Cord of the Rat

Syková

Svoboda

Polák

et al. 1994

J Cereb Blood Flow Metab

166

121

View full text Add to dashboard Cite

Summary: Extracellular space (ECS) volume fraction(IX), ECS tortuosity (A), and nonspecific uptake (k'), three parameters affecting the diffusion of substances in ner vous tissue, were studied during ischemia and anoxia in the rat spinal cord gray matter in vivo. Progressive isch emia evoked by exsanguination, as well as anoxia evoked by respiratory or cardiac arrest, produced prominent ex tracellular K + and pH changes closely related to a de crease in blood pressure and amplitude of field potentials. With use of ion-selective microelectrodes, the changes in the diffusion parameters were measured by quantitative analysis of concentration-time profiles of tetramethylam monium (TMA +) applied by iontophoresis concomitantly with ionic shifts. Under normoxic conditions (in rats with blood pressure of 80-110 mm Hg) diffusion parameters in the dorsal hom gray matter at depth 500-900 fLm were as follows: IX = 0.20 ± 0.019, A = 1.62 ± 0.12, k' = 4.6 ± 2.5 x 10-3 s -1 (mean ± SD, n = 39). Extracellular K +, pH, and diffusion properties gradually changed during progressive ischemia. As the blood pressure fell to 50-60 mm Hg and field potential amplitude to 20-60%, K + rose to 6-12 mM, pHe fell by -0.05-0.1 pH unit, and volume fraction of the ECS significantly decreased, to IX = 0.16 ± 0.019 (n = 22). Even though the tortuosity remained vir tually constant, the nonspecific uptake significantly de creased to k' = 3.4 ± 1.8 x 10-3 S-I. As the blood pressure fell to 20-30 mm Hg and field potential ampli tude to 0-6%, K + rose to 60-70 mM, pHe fell by -0.6-0.8 pH unit, and all three diffusion parameters significantly 301changed. The ECS volume fraction decreased to a = 0.05 ± 0.021, tortuosity increased to A = 2.00 ± 0.24, and TMA + uptake decreased to k' = 1.5 ± 1.6 x 10 -3 S -1 (n = 12). No further increase in extracellular K + or changes in the IX were found during and up to 120 min after the death of the animal. However, there was a further signif icant increase in A = 2.20 ± 0.14 and decrease in k' = 0.4 ± 0.3 x 10-3 s -1 (n = 24). The acid shift reached its maximum level at -5-10 min after respiratory arrest and then the pHe gradually increased by -0.2 unit. Full re covery to "normoxic" diffusion parameters was achieved after reinjection of the blood or after an injection of nor adrenaline during severe ischemia, if this resulted in a rise in blood pressure above 80 mm Hg and a decrease in extracellular K + below 12 mM. At -10 and 30 min after this recovery, the ECS volume fraction significantly in creased above "normoxic" values, to IX = 0.25 ± 0.016 (n = 7) and IX = 0.30 ± 0.021 (n = 6), respectively. The A and k' were not significantly different from the values found under normoxic conditions. Our data represent the first detailed in vivo measurements of diffusion parame ters IX, A, and k' during and after progressive ischemia and anoxia. The observed substantial changes in the diffusion parameters could affect the diffusion and aggravate the accumulation of ions, neurotransmitters, metabolic sub stances, and drugs ...

show abstract

“…Diffusion curves were digitized and recorded with a personal computer, where they were converted to concentration using the ISM calibration and analyzed with the programs Wanda and Walter (Hrabětová and Nicholson, 2007). The electrode array was aligned along a transverse axis at a depth of 400 m in the somatosensory neocortex; because the neocortex is isotropic (Lehmenkühler et al, 1993), measurement along a single axis suffices to determine ␣, , and kЈ.…”

Section: Methodsmentioning

confidence: 99%

“…These observations might be explained if ECS volume fraction ␣ (defined as the ratio of ECS volume to that of whole tissue) were increased by AQP4 deletion , delaying the accumulation and clearance of neuroactive substances in the ECS. After birth, ␣ is ϳ0.4 in rodent neocortex (Lehmenkühler et al, 1993) and shrinks to ϳ0.2 in the adult with a time course that matches glial proliferation and AQP4 expression (Wen et al, 1999). Consequently, it might be hypothesized that, in the absence of AQP4, this contraction of the ECS does not occur.…”

Section: Introductionmentioning

confidence: 99%

Aquaporin-4-Deficient Mice Have Increased Extracellular Space without Tortuosity Change

Yao¹,

Hrabětová²,

Nicholson³

et al. 2008

J. Neurosci.

Self Cite

136

113

View full text Add to dashboard Cite

Aquaporin-4 (AQP4) isϪ/Ϫ mice, and no differences in and k between the two genotypes. This is the first direct comparison of ECS properties in adult mice lacking AQP4 water channels with wild-type animals and demonstrates a significant enlargement of the volume fraction but no difference in hindrance to TMA ϩ diffusion, expressed as tortuosity. These findings provide direct evidence for involvement of AQP4 in modulation of the ECS volume fraction and provide a basis for future modeling of water and ion transport in the CNS.

show abstract

Extracellular space parameters in the rat neocortex and subcortical white matter during postnatal development determined by diffusion analysis

Cited by 273 publications

References 46 publications

Glial-conditional deletion of aquaporin-4 ( Aqp4 ) reduces blood–brain water uptake and confers barrier function on perivascular astrocyte endfeet

Glial-conditional deletion of aquaporin-4 ( Aqp4 ) reduces blood–brain water uptake and confers barrier function on perivascular astrocyte endfeet

Extracellular Volume Fraction and Diffusion Characteristics during Progressive Ischemia and Terminal Anoxia in the Spinal Cord of the Rat

Aquaporin-4-Deficient Mice Have Increased Extracellular Space without Tortuosity Change

Contact Info

Product

Resources

About