10 results on '"Kurtcuoglu, Vartan"'
Search Results
2. Large-scale morphometry of the subarachnoid space of the optic nerve
- Author
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Rossinelli, Diego, Killer, Hanspeter Esriel, Meyer, Peter, Knott, Graham, Fourestey, Gilles, Kurtcuoglu, Vartan, Kohler, Corina, Gruber, Philipp, Remonda, Luca, Neutzner, Albert, and Berberat, Jatta
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- 2023
- Full Text
- View/download PDF
3. Are standing osmotic gradients the main driver of cerebrospinal fluid production? A computational analysis
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Razzaghi Khamesi, Pooya, Charitatos, Vasileios, Heerfordt, Eva K., MacAulay, Nanna, and Kurtcuoglu, Vartan
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- 2023
- Full Text
- View/download PDF
4. Membrane transporters control cerebrospinal fluid formation independently of conventional osmosis to modulate intracranial pressure
- Author
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Oernbo, Eva K., Steffensen, Annette B., Razzaghi Khamesi, Pooya, Toft-Bertelsen, Trine L., Barbuskaite, Dagne, Vilhardt, Frederik, Gerkau, Niklas J., Tritsaris, Katerina, Simonsen, Anja H., Lolansen, Sara D., Andreassen, Søren N., Hasselbalch, Steen G., Zeuthen, Thomas, Rose, Christine R., Kurtcuoglu, Vartan, and MacAulay, Nanna
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- 2022
- Full Text
- View/download PDF
5. Characterising spinal cerebrospinal fluid flow in the pig with phase-contrast magnetic resonance imaging
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Bessen, Madeleine Amy; https://orcid.org/0000-0003-0369-6448, Gayen, Christine Diana; https://orcid.org/0000-0002-1877-275X, Quarrington, Ryan David; https://orcid.org/0000-0002-0633-2482, Walls, Angela Catherine; https://orcid.org/0000-0001-9489-2991, Leonard, Anna Victoria; https://orcid.org/0000-0002-9430-3314, Kurtcuoglu, Vartan; https://orcid.org/0000-0003-2665-0995, Jones, Claire Frances; https://orcid.org/0000-0002-0995-1182, Bessen, Madeleine Amy; https://orcid.org/0000-0003-0369-6448, Gayen, Christine Diana; https://orcid.org/0000-0002-1877-275X, Quarrington, Ryan David; https://orcid.org/0000-0002-0633-2482, Walls, Angela Catherine; https://orcid.org/0000-0001-9489-2991, Leonard, Anna Victoria; https://orcid.org/0000-0002-9430-3314, Kurtcuoglu, Vartan; https://orcid.org/0000-0003-2665-0995, and Jones, Claire Frances; https://orcid.org/0000-0002-0995-1182
- Abstract
Background: Detecting changes in pulsatile cerebrospinal fluid (CSF) flow may assist clinical management decisions, but spinal CSF flow is relatively understudied. Traumatic spinal cord injuries (SCI) often cause spinal cord swelling and subarachnoid space (SAS) obstruction, potentially causing pulsatile CSF flow changes. Pigs are emerging as a favoured large animal SCI model; therefore, the aim of this study was to characterise CSF flow along the healthy pig spine. Methods: Phase-contrast magnetic resonance images (PC-MRI), retrospectively cardiac gated, were acquired for fourteen laterally recumbent, anaesthetised and ventilated, female domestic pigs (22–29 kg). Axial images were obtained at C2/C3, T8/T9, T11/T12 and L1/L2. Dorsal and ventral SAS regions of interest (ROI) were manually segmented. CSF flow and velocity were determined throughout a cardiac cycle. Linear mixed-effects models, with post-hoc comparisons, were used to identify differences in peak systolic/diastolic flow, and maximum velocity (cranial/caudal), across spinal levels and dorsal/ventral SAS. Velocity wave speed from C2/C3 to L1/L2 was calculated. Results: PC-MRI data were obtained for 11/14 animals. Pulsatile CSF flow was observed at all spinal levels. Peak systolic flow was greater at C2/C3 (dorsal: − 0.32 ± 0.14 mL/s, ventral: − 0.15 ± 0.13 mL/s) than T8/T9 dorsally (− 0.04 ± 0.03 mL/s; p < 0.001), but not different ventrally (− 0.08 ± 0.08 mL/s; p = 0.275), and no difference between thoracolumbar levels (p > 0.05). Peak diastolic flow was greater at C2/C3 (0.29 ± 0.08 mL/s) compared to T8/T9 (0.03 ± 0.03 mL/s, p < 0.001) dorsally, but not different ventrally (p = 1.000). Cranial and caudal maximum velocity at C2/C3 were greater than thoracolumbar levels dorsally (p < 0.001), and T8/T9 and L1/L2 ventrally (p = 0.022). Diastolic velocity wave speed was 1.41 ± 0.39 m/s dorsally and 1.22 ± 0.21 m/s ventrally, and systolic velocity wave speed was 1.02 ± 0.25 m/s dorsally and 0.91 ± 0.22 m/s ve
- Published
- 2023
6. Membrane transporters control cerebrospinal fluid formation independently of conventional osmosis to modulate intracranial pressure
- Author
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Oernbo, Eva K, Steffensen, Annette B, Razzaghi Khamesi, Pooya, Toft-Bertelsen, Trine L, Barbuskaite, Dagne, Vilhardt, Frederik, Gerkau, Niklas J, Tritsaris, Katerina, Simonsen, Anja H, Lolansen, Sara D, Andreassen, Søren N, Hasselbalch, Steen G, Zeuthen, Thomas, Rose, Christine R, Kurtcuoglu, Vartan; https://orcid.org/0000-0003-2665-0995, MacAulay, Nanna; https://orcid.org/0000-0002-7800-6600, Oernbo, Eva K, Steffensen, Annette B, Razzaghi Khamesi, Pooya, Toft-Bertelsen, Trine L, Barbuskaite, Dagne, Vilhardt, Frederik, Gerkau, Niklas J, Tritsaris, Katerina, Simonsen, Anja H, Lolansen, Sara D, Andreassen, Søren N, Hasselbalch, Steen G, Zeuthen, Thomas, Rose, Christine R, Kurtcuoglu, Vartan; https://orcid.org/0000-0003-2665-0995, and MacAulay, Nanna; https://orcid.org/0000-0002-7800-6600
- Abstract
Background: Disturbances in the brain fluid balance can lead to life-threatening elevation in the intracranial pressure (ICP), which represents a vast clinical challenge. Nevertheless, the details underlying the molecular mechanisms governing cerebrospinal fluid (CSF) secretion are largely unresolved, thus preventing targeted and efficient pharmaceutical therapy of cerebral pathologies involving elevated ICP. Methods: Experimental rats were employed for in vivo determinations of CSF secretion rates, ICP, blood pressure and ex vivo excised choroid plexus for morphological analysis and quantification of expression and activity of various transport proteins. CSF and blood extractions from rats, pigs, and humans were employed for osmolality determinations and a mathematical model employed to determine a contribution from potential local gradients at the surface of choroid plexus. Results: We demonstrate that CSF secretion can occur independently of conventional osmosis and that local osmotic gradients do not suffice to support CSF secretion. Instead, the CSF secretion across the luminal membrane of choroid plexus relies approximately equally on the Na$^{+}$/K$^{+}$/2Cl$^{−}$ cotransporter NKCC1, the Na$^{+}$/HCO$_{3}$$^{−}$ cotransporter NBCe2, and the Na$^{+}$/K$^{+}$-ATPase, but not on the Na$^{+}$/H$^{+}$ exchanger NHE1. We demonstrate that pharmacological modulation of CSF secretion directly affects the ICP. Conclusions: CSF secretion appears to not rely on conventional osmosis, but rather occur by a concerted effort of different choroidal transporters, possibly via a molecular mode of water transport inherent in the proteins themselves. Therapeutic modulation of the rate of CSF secretion may be employed as a strategy to modulate ICP. These insights identify new promising therapeutic targets against brain pathologies associated with elevated ICP.
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- 2022
7. Is posture-related craniospinal compliance shift caused by jugular vein collapse? A theoretical analysis
- Author
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Gehlen, Manuel, Kurtcuoglu, Vartan, Schmid Daners, Marianne, University of Zurich, and Gehlen, Manuel
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Research ,Posture ,2804 Cellular and Molecular Neuroscience ,610 Medicine & health ,Blood Pressure ,Cerebrospinal fluid dynamics ,Models, Biological ,10052 Institute of Physiology ,2806 Developmental Neuroscience ,Craniospinal ,10076 Center for Integrative Human Physiology ,2808 Neurology ,Pressure ,570 Life sciences ,biology ,Humans ,Compliance ,10064 Neuroscience Center Zurich ,Jugular Veins ,Algorithms ,Cerebrospinal Fluid - Abstract
Background: Postural changes are related to changes in cerebrospinal fluid (CSF) dynamics. While sitting up leads to a decrease in cranial CSF pressure, it also causes shifts in the craniospinal CSF volume and compliance distribution. We hypothesized that jugular vein collapse in upright posture is a major contributor to these shifts in CSF volume and compliance. Methods: To test this hypothesis, we implemented a mathematical lumped-parameter model of the CSF system and the relevant parts of the cardiovascular system. In this model, the CSF and the venous system are each divided into a cranial and a spinal part. The pressures in these cranial and spinal portions differ by the posture-dependent hydrostatic pressure columns in the connecting vessels. Jugular collapse is represented by a reduction of the hydrostatic pressure difference between cranial and spinal veins. The CSF pressure–volume relationship is implemented as a function of the local CSF to venous pressure gradient. This implies that an increase in CSF volume leads to a simultaneous displacement of blood from adjacent veins. CSF pulsations driven by the cardiovascular system are introduced through a pulsating cranial arterial volume. Results: In upright posture, the implemented CSF pressure–volume relationship shifts to lower cranial CSF pressures compared to the horizontal position, leading to a decrease in cranial CSF pressure when sitting up. Concurrently, the compliance of the spinal compartment decreases while the one of the cranial compartment increases. With this, in upright posture only 10% of the CSF system’s compliance is provided by the spinal compartment compared to 35% in horizontal posture. This reduction in spinal compliance is accompanied by a caudal shift of CSF volume. Also, the ability of the spinal CSF compartment to compensate for cerebral arterial volume pulsations reduces in upright posture, which in turn reduces the calculated craniospinal CSF flow pulsations. Conclusion: The mathematical model enabled us to isolate the effect of jugular collapse and quantify the induced shifts of compliance and CSF volume. The good concordance of the modelled changes with clinically observed values indicates that jugular collapse can be considered a major contributor to CSF dynamics in upright posture., Fluids and Barriers of the CNS, 14 (1), ISSN:2045-8118
- Published
- 2017
8. Is posture-related craniospinal compliance shift caused by jugular vein collapse? A theoretical analysis
- Author
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Gehlen, Manuel; https://orcid.org/0000-0001-6393-9136, Kurtcuoglu, Vartan, Schmid Daners, Marianne, Gehlen, Manuel; https://orcid.org/0000-0001-6393-9136, Kurtcuoglu, Vartan, and Schmid Daners, Marianne
- Abstract
BACKGROUND Postural changes are related to changes in cerebrospinal fluid (CSF) dynamics. While sitting up leads to a decrease in cranial CSF pressure, it also causes shifts in the craniospinal CSF volume and compliance distribution. We hypothesized that jugular vein collapse in upright posture is a major contributor to these shifts in CSF volume and compliance. METHODS To test this hypothesis, we implemented a mathematical lumped-parameter model of the CSF system and the relevant parts of the cardiovascular system. In this model, the CSF and the venous system are each divided into a cranial and a spinal part. The pressures in these cranial and spinal portions differ by the posture-dependent hydrostatic pressure columns in the connecting vessels. Jugular collapse is represented by a reduction of the hydrostatic pressure difference between cranial and spinal veins. The CSF pressure-volume relationship is implemented as a function of the local CSF to venous pressure gradient. This implies that an increase in CSF volume leads to a simultaneous displacement of blood from adjacent veins. CSF pulsations driven by the cardiovascular system are introduced through a pulsating cranial arterial volume. RESULTS In upright posture, the implemented CSF pressure-volume relationship shifts to lower cranial CSF pressures compared to the horizontal position, leading to a decrease in cranial CSF pressure when sitting up. Concurrently, the compliance of the spinal compartment decreases while the one of the cranial compartment increases. With this, in upright posture only 10% of the CSF system's compliance is provided by the spinal compartment compared to 35% in horizontal posture. This reduction in spinal compliance is accompanied by a caudal shift of CSF volume. Also, the ability of the spinal CSF compartment to compensate for cerebral arterial volume pulsations reduces in upright posture, which in turn reduces the calculated craniospinal CSF flow pulsations. CONCLUSION The mathematic
- Published
- 2017
9. Barrier dysfunction or drainage reduction: differentiating causes of CSF protein increase.
- Author
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Asgari, Mahdi, de Zélicourt, Diane A., and Kurtcuoglu, Vartan
- Subjects
CEREBROSPINAL fluid ,PROTEINS ,CENTRAL nervous system ,BODY fluids ,NERVOUS system - Abstract
Background: Cerebrospinal fluid (CSF) protein analysis is an important element in the diagnostic chain for various central nervous system (CNS) pathologies. Among multiple existing approaches to interpreting measured protein levels, the Reiber diagram is particularly robust with respect to physiologic inter-individual variability, as it uses multiple subject-specific anchoring values. Beyond reliable identification of abnormal protein levels, the Reiber diagram has the potential to elucidate their pathophysiologic origin. In particular, both reduction of CSF drainage from the craniospinal space as well as blood--CNS barrier dysfunction have been suggested pas possible causes of increased concentration of blood-derived proteins. However, there is disagreement on which of the two is the true cause. Methods: We designed two computational models to investigate the mechanisms governing protein distribution in the spinal CSF. With a one-dimensional model, we evaluated the distribution of albumin and immunoglobulin G (IgG), accounting for protein transport rates across blood--CNS barriers, CSF dynamics (including both dispersion induced by CSF pulsations and advection by mean CSF flow) and CSF drainage. Dispersion coefficients were determined a priori by computing the axisymmetric three-dimensional CSF dynamics and solute transport in a representative segment of the spinal canal. Results: Our models reproduce the empirically determined hyperbolic relation between albumin and IgG quotients. They indicate that variation in CSF drainage would yield a linear rather than the expected hyperbolic profile. In contrast, modelled barrier dysfunction reproduces the experimentally observed relation. Conclusions: High levels of albumin identified in the Reiber diagram are more likely to originate from a barrier dysfunction than from a reduction in CSF drainage. Our in silico experiments further support the hypothesis of decreasing spinal CSF drainage in rostro-caudal direction and emphasize the physiological importance of pulsation-driven dispersion for the transport of large molecules in the CSF. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
10. Barrier dysfunction or drainage reduction: differentiating causes of CSF protein increase
- Author
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Mahdi Asgari, Vartan Kurtcuoglu, Diane de Zélicourt, University of Zurich, and Kurtcuoglu, Vartan
- Subjects
0301 basic medicine ,Pathology ,Spinal Subarachnoid Space ,2804 Cellular and Molecular Neuroscience ,lcsh:RC346-429 ,Immunoglobulin G ,10052 Institute of Physiology ,0302 clinical medicine ,Cerebrospinal fluid ,10064 Neuroscience Center Zurich ,Drainage ,CSF albumin ,Cerebrospinal Fluid Leak ,Cerebrospinal Fluid Proteins ,General Medicine ,Blood Proteins ,Protein distribution ,Transport protein ,medicine.anatomical_structure ,Neurology ,Blood-Brain Barrier ,10076 Center for Integrative Human Physiology ,Barrier Permeability ,medicine.medical_specialty ,Central nervous system ,610 Medicine & health ,Biology ,Models, Biological ,2806 Developmental Neuroscience ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Dispersion Coefficient ,Developmental Neuroscience ,Albumins ,medicine ,Humans ,Computer Simulation ,lcsh:Neurology. Diseases of the nervous system ,Research ,Albumin ,Biological Transport ,030104 developmental biology ,2808 Neurology ,biology.protein ,Biophysics ,570 Life sciences ,biology ,Albumin Quotient ,Spinal Canal ,030217 neurology & neurosurgery - Abstract
Background Cerebrospinal fluid (CSF) protein analysis is an important element in the diagnostic chain for various central nervous system (CNS) pathologies. Among multiple existing approaches to interpreting measured protein levels, the Reiber diagram is particularly robust with respect to physiologic inter-individual variability, as it uses multiple subject-specific anchoring values. Beyond reliable identification of abnormal protein levels, the Reiber diagram has the potential to elucidate their pathophysiologic origin. In particular, both reduction of CSF drainage from the cranio-spinal space as well as blood–CNS barrier dysfunction have been suggested ρas possible causes of increased concentration of blood-derived proteins. However, there is disagreement on which of the two is the true cause. Methods We designed two computational models to investigate the mechanisms governing protein distribution in the spinal CSF. With a one-dimensional model, we evaluated the distribution of albumin and immunoglobulin G (IgG), accounting for protein transport rates across blood–CNS barriers, CSF dynamics (including both dispersion induced by CSF pulsations and advection by mean CSF flow) and CSF drainage. Dispersion coefficients were determined a priori by computing the axisymmetric three-dimensional CSF dynamics and solute transport in a representative segment of the spinal canal. Results Our models reproduce the empirically determined hyperbolic relation between albumin and IgG quotients. They indicate that variation in CSF drainage would yield a linear rather than the expected hyperbolic profile. In contrast, modelled barrier dysfunction reproduces the experimentally observed relation. Conclusions High levels of albumin identified in the Reiber diagram are more likely to originate from a barrier dysfunction than from a reduction in CSF drainage. Our in silico experiments further support the hypothesis of decreasing spinal CSF drainage in rostro-caudal direction and emphasize the physiological importance of pulsation-driven dispersion for the transport of large molecules in the CSF.
- Published
- 2017
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