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Virchow-Robin space and aquaporin-4: new insights on an old friend.

Nakada T - Croat. Med. J. (2014)

Bottom Line: Autoregulation of brain blood flow serves to maintain a constant inner capillary fluid pressure, allowing fluid pressure of the Virchow Robin space to regulate regional cerebral blood flow (rCBF) based on AQP-4 gating.Excess heat produced by neural activities is effectively removed from the area of activation by increased rCBF by closing AQP-4 channels.This neural flow coupling (NFC) is likely mediated by heat generated proton channels.

View Article: PubMed Central - PubMed

Affiliation: Tsutomu Nakada, Center for Integrated Human Brain Science, Brain Research Institute, University of Niigata, 1-757 Asahimachi, Niigata, 951-8585, Japan, tnakada@bri.niigata-u.ac.jp.

ABSTRACT
Recent studies have strongly indicated that the classic circulation model of cerebrospinal fluid (CSF) is no longer valid. The production of CSF is not only dependent on the choroid plexus but also on water flux in the peri-capillary (Virchow Robin) space. Historically, CSF flow through the Virchow Robin space is known as interstitial flow, the physiological significance of which is now fully understood. This article briefly reviews the modern concept of CSF physiology and the Virchow-Robin space, in particular its functionalities critical for central nervous system neural activities. Water influx into the Virchow Robin space and, hence, interstitial flow is regulated by aquaporin-4 (AQP-4) localized in the endfeet of astrocytes, connecting the intracellular cytosolic fluid space of astrocytes and the Virchow Robin space. Interstitial flow has a functionality equivalent to systemic lymphatics, on which clearance of β-amyloid is strongly dependent. Autoregulation of brain blood flow serves to maintain a constant inner capillary fluid pressure, allowing fluid pressure of the Virchow Robin space to regulate regional cerebral blood flow (rCBF) based on AQP-4 gating. Excess heat produced by neural activities is effectively removed from the area of activation by increased rCBF by closing AQP-4 channels. This neural flow coupling (NFC) is likely mediated by heat generated proton channels.

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Related in: MedlinePlus

Water influx study in transgenic mice. H2O17 JJ vicinal coupling proton exchange (JJVCPE) imaging dynamic study showed that only senile plaque bearing transgenic mice (5xFamilial Alzheimer Disease [FAD]) showed a decline in water influx into the cerebrospinal fluid (CSF) system similar to aquaporin-4 (AQP-4) knockout mice. β-amyloid overproducing transgenic mice without senile plaque formation (C2a-5FAD) showed a virtually identical influx with control mice (C57/BL6). The study indicates that disturbance in β-amyloid clearance through the interstitial flow play a critical, if not sole, role in the pathogenesis of Alzheimer disease.
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Figure 3: Water influx study in transgenic mice. H2O17 JJ vicinal coupling proton exchange (JJVCPE) imaging dynamic study showed that only senile plaque bearing transgenic mice (5xFamilial Alzheimer Disease [FAD]) showed a decline in water influx into the cerebrospinal fluid (CSF) system similar to aquaporin-4 (AQP-4) knockout mice. β-amyloid overproducing transgenic mice without senile plaque formation (C2a-5FAD) showed a virtually identical influx with control mice (C57/BL6). The study indicates that disturbance in β-amyloid clearance through the interstitial flow play a critical, if not sole, role in the pathogenesis of Alzheimer disease.

Mentions: The basic function of lymphatic is drainage of cellular debris subjected to molecular scrutiny before returning to venous circulation. Water influx into the CSF system through the Virchow Robin space is likely to play an essential role in clearing toxic proteins from the brain parenchyma. One of the most intriguing examples is β-amyloid. Interstitial flow is shown to be responsible for β-amyloid clearance (8,9,14). Senile plaque bearing transgenic mice showed significant decline in water influx into the CSF system to the extent similar to AQP-4 knockout mice (19). In contrast, transgenic mice with enhanced production of β-amyloid, but without senile plaque formation, showed normal influx into the CSF through the Virchow Robin space (Figure 3).


Virchow-Robin space and aquaporin-4: new insights on an old friend.

Nakada T - Croat. Med. J. (2014)

Water influx study in transgenic mice. H2O17 JJ vicinal coupling proton exchange (JJVCPE) imaging dynamic study showed that only senile plaque bearing transgenic mice (5xFamilial Alzheimer Disease [FAD]) showed a decline in water influx into the cerebrospinal fluid (CSF) system similar to aquaporin-4 (AQP-4) knockout mice. β-amyloid overproducing transgenic mice without senile plaque formation (C2a-5FAD) showed a virtually identical influx with control mice (C57/BL6). The study indicates that disturbance in β-amyloid clearance through the interstitial flow play a critical, if not sole, role in the pathogenesis of Alzheimer disease.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4157385&req=5

Figure 3: Water influx study in transgenic mice. H2O17 JJ vicinal coupling proton exchange (JJVCPE) imaging dynamic study showed that only senile plaque bearing transgenic mice (5xFamilial Alzheimer Disease [FAD]) showed a decline in water influx into the cerebrospinal fluid (CSF) system similar to aquaporin-4 (AQP-4) knockout mice. β-amyloid overproducing transgenic mice without senile plaque formation (C2a-5FAD) showed a virtually identical influx with control mice (C57/BL6). The study indicates that disturbance in β-amyloid clearance through the interstitial flow play a critical, if not sole, role in the pathogenesis of Alzheimer disease.
Mentions: The basic function of lymphatic is drainage of cellular debris subjected to molecular scrutiny before returning to venous circulation. Water influx into the CSF system through the Virchow Robin space is likely to play an essential role in clearing toxic proteins from the brain parenchyma. One of the most intriguing examples is β-amyloid. Interstitial flow is shown to be responsible for β-amyloid clearance (8,9,14). Senile plaque bearing transgenic mice showed significant decline in water influx into the CSF system to the extent similar to AQP-4 knockout mice (19). In contrast, transgenic mice with enhanced production of β-amyloid, but without senile plaque formation, showed normal influx into the CSF through the Virchow Robin space (Figure 3).

Bottom Line: Autoregulation of brain blood flow serves to maintain a constant inner capillary fluid pressure, allowing fluid pressure of the Virchow Robin space to regulate regional cerebral blood flow (rCBF) based on AQP-4 gating.Excess heat produced by neural activities is effectively removed from the area of activation by increased rCBF by closing AQP-4 channels.This neural flow coupling (NFC) is likely mediated by heat generated proton channels.

View Article: PubMed Central - PubMed

Affiliation: Tsutomu Nakada, Center for Integrated Human Brain Science, Brain Research Institute, University of Niigata, 1-757 Asahimachi, Niigata, 951-8585, Japan, tnakada@bri.niigata-u.ac.jp.

ABSTRACT
Recent studies have strongly indicated that the classic circulation model of cerebrospinal fluid (CSF) is no longer valid. The production of CSF is not only dependent on the choroid plexus but also on water flux in the peri-capillary (Virchow Robin) space. Historically, CSF flow through the Virchow Robin space is known as interstitial flow, the physiological significance of which is now fully understood. This article briefly reviews the modern concept of CSF physiology and the Virchow-Robin space, in particular its functionalities critical for central nervous system neural activities. Water influx into the Virchow Robin space and, hence, interstitial flow is regulated by aquaporin-4 (AQP-4) localized in the endfeet of astrocytes, connecting the intracellular cytosolic fluid space of astrocytes and the Virchow Robin space. Interstitial flow has a functionality equivalent to systemic lymphatics, on which clearance of β-amyloid is strongly dependent. Autoregulation of brain blood flow serves to maintain a constant inner capillary fluid pressure, allowing fluid pressure of the Virchow Robin space to regulate regional cerebral blood flow (rCBF) based on AQP-4 gating. Excess heat produced by neural activities is effectively removed from the area of activation by increased rCBF by closing AQP-4 channels. This neural flow coupling (NFC) is likely mediated by heat generated proton channels.

Show MeSH
Related in: MedlinePlus