Application of fluorescent dextrans to the brain surface under constant pressure reveals AQP4-independent solute uptake
| العنوان: | Application of fluorescent dextrans to the brain surface under constant pressure reveals AQP4-independent solute uptake |
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| المؤلفون: | Alan S. Verkman, Alex J. Smith, Dan Song, Gökhan Akdemir, Meetu Wadhwa |
| المصدر: | The Journal of general physiology, vol 153, iss 8 The Journal of General Physiology |
| بيانات النشر: | eScholarship, University of California, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Physiology, 1.1 Normal biological development and functioning, Medical Physiology, Article, 03 medical and health sciences, Mice, 0302 clinical medicine, Cerebrospinal fluid, Interstitial space, Interstitial fluid, Underpinning research, medicine, Extracellular, Animals, Compartment (pharmacokinetics), Intracranial pressure, Aquaporin 4, Chemistry, Neurosciences, Brain, Extracellular Fluid, Dextrans, Biological Transport, Brain Disorders, 030104 developmental biology, medicine.anatomical_structure, Neurological, Biophysics, Glymphatic system, Cellular Physiology, Systems Physiology, Subarachnoid space, 030217 neurology & neurosurgery |
| الوصف: | Smith et al. use a novel technique for direct measurement of solute transport from cerebrospinal fluid to brain interstitial fluid. Contrary to previous suggestions, they find no evidence for a role of aquaporin-4 in this process of extracellular transport in the central nervous system. Extracellular solutes in the central nervous system are exchanged between the interstitial fluid, the perivascular compartment, and the cerebrospinal fluid (CSF). The “glymphatic” mechanism proposes that the astrocyte water channel aquaporin-4 (AQP4) is a major determinant of solute transport between the CSF and the interstitial space; however, this is controversial in part because of wide variance in experimental data on interstitial uptake of cisternally injected solutes. Here, we investigated the determinants of solute uptake in brain parenchyma following cisternal injection and reexamined the role of AQP4 using a novel constant-pressure method. In mice, increased cisternal injection rate, which modestly increased intracranial pressure, remarkably increased solute dispersion in the subarachnoid space and uptake in the cortical perivascular compartment. To investigate the role of AQP4 in the absence of confounding variations in pressure and CSF solute concentration over time and space, solutes were applied directly onto the brain surface after durotomy under constant external pressure. Pressure elevation increased solute penetration into the perivascular compartment but had little effect on parenchymal solute uptake. Solute penetration and uptake did not differ significantly between wild-type and AQP4 knockout mice. Our results offer an explanation for the variability in cisternal injection studies and indicate AQP4-independent solute transfer from the CSF to the interstitial space in mouse brain. |
| وصف الملف: | application/pdf |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::105ce1e07d609d45fae1d9d8dd3c4cdf https://escholarship.org/uc/item/1nv274s3 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....105ce1e07d609d45fae1d9d8dd3c4cdf |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |