**2.1 The glymphatic pathway and the Virchow Robin (paravascular) spaces**

The amount of CSF within the CSF compartments is a consequence of the net filtration and absorption of water through the selectively permeable capillary walls traversing through the brain tissue. This net effect is governed by the physiological

**207**

**Figure 3.**

**Figure 2.**

*Brain Cooling and Cleaning: A New Perspective in Cerebrospinal Fluid (CSF) Dynamics*

or pathological conditions prevailing within these compartments. The glymphatic system branches along the course of the arteries, arterioles, capillaries, and venules, forming a paravascular cast. This CSF interacts with the end feet of glia and indirectly with neurons to establish an exchange with the brain ISF (**Figure 2**).

The AQP4 channels mediate the bidirectional transport of water in response to passive osmotic and hydraulic pressure gradients [2, 3], resulting in the CSF-ISF exchange [4]. This makes the glymphatic system extremely pressure dependent. Any increase of pressure in the glymphatic system would produce the passage of fluid toward the interstitial space until the pressure in both compartments is equalized. This exchange drives the removal of exogenous molecules from the interstitial

*Artistic representation that depicts the persistence of the paravascular system through the arteries, arterioles, capillaries, venules, and veins. This indicates that just as there is a vascular cast of the brain, there is a* 

*The anatomy of the Virchow Robin spaces forming an extensive network of communication within the* 

*paravascular system cast as well. Courtesy: Cherian and Beltran [1].*

*glymphatic pathway. Courtesy: Orešković and Klarica [7].*

*DOI: http://dx.doi.org/10.5772/intechopen.90484*

spaces of the brain [5, 6] (**Figure 3**).

### *Brain Cooling and Cleaning: A New Perspective in Cerebrospinal Fluid (CSF) Dynamics DOI: http://dx.doi.org/10.5772/intechopen.90484*

or pathological conditions prevailing within these compartments. The glymphatic system branches along the course of the arteries, arterioles, capillaries, and venules, forming a paravascular cast. This CSF interacts with the end feet of glia and indirectly with neurons to establish an exchange with the brain ISF (**Figure 2**).

The AQP4 channels mediate the bidirectional transport of water in response to passive osmotic and hydraulic pressure gradients [2, 3], resulting in the CSF-ISF exchange [4]. This makes the glymphatic system extremely pressure dependent. Any increase of pressure in the glymphatic system would produce the passage of fluid toward the interstitial space until the pressure in both compartments is equalized. This exchange drives the removal of exogenous molecules from the interstitial spaces of the brain [5, 6] (**Figure 3**).

#### **Figure 2.**

*New Insight into Cerebrovascular Diseases - An Updated Comprehensive Review*

**2. Cerebrospinal fluid: dynamics and function**

*The anatomy of the fluid compartments of the brain: ventricular and cisternal systems.*

function of the CSF in a unique perspective.

cal buffer for brain functioning.

Adult CSF volume is estimated to be 150 ml with a distribution of 125 ml within

the subarachnoid spaces and 25 ml within the ventricles. This difference in the volume of CSF between the two compartments is important to understand the

The CSF secretion varies between individuals, usually ranging between 400 and 600 ml per day in an adult. The constant secretion of CSF contributes to a four to five times turnover per 24-h period. This turnover is of immense importance in exploring the functions of the CSF which have not yet been understood quite well. While the CSF has been considered as a source of nutrition and waste removal and a mechanically buoyant substance, cushioning the brain, the newer insights of the glymphatic pathways have demonstrated a critical role of CSF flow as a physiologi-

With a closely regulated composition, the CSF is valuable in analyzing cerebral pathologies. Alterations in the regulation of localized temperatures, malformation of proteins, and impeding clearance of pathologic proteins are the pathophysiological mechanisms for onset and progress of most neurodegenerative disorders as well as secondary brain damage in the setting of trauma. It is, however, interesting to analyze how the impairment of CSF inflow or outflow through the glymphatic system might lead to the cascade of these degenerative and traumatic pathologies.

**2.1 The glymphatic pathway and the Virchow Robin (paravascular) spaces**

The amount of CSF within the CSF compartments is a consequence of the net filtration and absorption of water through the selectively permeable capillary walls traversing through the brain tissue. This net effect is governed by the physiological

**206**

**Figure 1.**

*Artistic representation that depicts the persistence of the paravascular system through the arteries, arterioles, capillaries, venules, and veins. This indicates that just as there is a vascular cast of the brain, there is a paravascular system cast as well. Courtesy: Cherian and Beltran [1].*

#### **Figure 3.**

*The anatomy of the Virchow Robin spaces forming an extensive network of communication within the glymphatic pathway. Courtesy: Orešković and Klarica [7].*

#### **Figure 4.**

*Schematic representation of the mechanism of CSF-shift edema following traumatic brain injury. The AQP-4 channels on the lining of VRS allow the shift of CSF from the cisterns into the brain parenchyma leading to brain edema.*

### **2.2 Introducing the concept of "CSF-shift" edema**

The dependence of AQP4 to pressure gradients in both senses might be the underlying mechanism leading to the recently described "shift edema" following trauma [8] and also would explain the advantages of cisternostomy over craniectomy for the treatment in the short- and long-term follow-up of the patients [9]. Subsequent to subarachnoid hemorrhage, red blood cells are confined to the subarachnoid space and do not enter the VRS as pial membranes between the PVS and the SAS prevent the exchange of large molecules [10] (**Figure 4**).
