**3. Brain as a water-cooled and water-cleaned system**

#### **3.1 The subarachnoid cisterns and paranasal sinuses: anatomical relationships**

The brain can be assumed as a water-cooled system with the CSF as a medium of heat removal and the paranasal sinuses as cooling surfaces. The close contact of the PNS with the suprasellar cisterns helps create a radiation system, and the mechanical process of breathing allows the sinuses to deliver the acquired heat from the brain parenchyma which is dumped by the CSF residing in the cisterns. Evaporation at the sinus surface causes cooling effect that is transmitted to the cisterns, dissipating the heat from the CSF which is acquired from the brain parenchyma [1] (**Figure 5**).

This cooling unit can be hypothesized to be a fundamental thermostat, and any hindrance in CSF flow might explain the cascade of protein misfolding secondary to heat accumulation as seen in neurodegeneration. While brain cooling is a passive process that occurs throughout the day, brain cleaning is more pronounced nocturnally. It is believed that brain cleaning is regulated by AQP4 and exchanges between interstitial fluid and CSF have been demonstrated to be more

**209**

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

active during sleep due to an expansion of the extracellular space, being increased by 60% during sleep [11], particularly in the lateral position [12]. The increased glymphatic clearance of the metabolic waste products generated by neural activity in the awake brain occurs during sleep, explaining the need to sleep for restoring

*Close communication of the paranasal sinuses with the cisterns creating a brain cooling unit. Courtesy: Cherian* 

**3.2 Hypothesis of the CSF-driven brain cooling and cleaning mechanism**

CSF is permanently produced and absorbed in the whole CSF system as a consequence of filtration and reabsorption of water volume through the capillary walls into the surrounding brain tissue. The three- to fourfold turnover rate in CSF production allows for a rigorous cerebral buffering at physiological states which helps maintain brain function. The brain generates tremendous amount of heat throughout the day which needs to be removed essentially to prevent protein misfolding and generation of free radicals. This warrants a system to allow for heat removal in the form of cooling as well as cleaning of metabolic wastes to prevent

At a physiological state, the difference in arterial and venous hydrostatic and osmotic pressures allows a unidirectional flow of water and other molecules (soluble waste), with water leaving from the arterial end and molecules entering at the venous end. This simultaneous exchange of water and waste at two different ends

A deeper insight to this simultaneous exchange of water and waste in the blood vessels reveals the orientation of the brain vasculature, which, unlike other organs, runs in an opposite fashion, with the primary arteries lying ventral and more medially, whereas the principal veins run in a dorsal and lateral manner. Additionally, the disposition of white matter tracts creates an anisotropic field that facilitates the direction of fluid and molecules toward the main veins, which is further directed by

The paravascular system therefore maintains a very intricate and evolved system

through extensive branching of vessels in the brain along with its paravascular

can thus be regarded as a means of cleaning for the brain [5].

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

alertness and activity.

**Figure 5.**

*and Beltran [1].*

accumulation of toxic metabolites.

changes in arteriovenous pressure gradients.

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

#### **Figure 5.**

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

**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

*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* 

**3.1 The subarachnoid cisterns and paranasal sinuses: anatomical relationships**

The brain can be assumed as a water-cooled system with the CSF as a medium of heat removal and the paranasal sinuses as cooling surfaces. The close contact of the PNS with the suprasellar cisterns helps create a radiation system, and the mechanical process of breathing allows the sinuses to deliver the acquired heat from the brain parenchyma which is dumped by the CSF residing in the cisterns. Evaporation at the sinus surface causes cooling effect that is transmitted to the cisterns, dissipating the heat from the CSF which is acquired from the brain parenchyma [1] (**Figure 5**). This cooling unit can be hypothesized to be a fundamental thermostat, and any hindrance in CSF flow might explain the cascade of protein misfolding secondary to heat accumulation as seen in neurodegeneration. While brain cooling is a passive process that occurs throughout the day, brain cleaning is more pronounced nocturnally. It is believed that brain cleaning is regulated by AQP4 and exchanges between interstitial fluid and CSF have been demonstrated to be more

and the SAS prevent the exchange of large molecules [10] (**Figure 4**).

**3. Brain as a water-cooled and water-cleaned system**

**208**

**Figure 4.**

*brain edema.*

*Close communication of the paranasal sinuses with the cisterns creating a brain cooling unit. Courtesy: Cherian and Beltran [1].*

active during sleep due to an expansion of the extracellular space, being increased by 60% during sleep [11], particularly in the lateral position [12]. The increased glymphatic clearance of the metabolic waste products generated by neural activity in the awake brain occurs during sleep, explaining the need to sleep for restoring alertness and activity.

#### **3.2 Hypothesis of the CSF-driven brain cooling and cleaning mechanism**

CSF is permanently produced and absorbed in the whole CSF system as a consequence of filtration and reabsorption of water volume through the capillary walls into the surrounding brain tissue. The three- to fourfold turnover rate in CSF production allows for a rigorous cerebral buffering at physiological states which helps maintain brain function. The brain generates tremendous amount of heat throughout the day which needs to be removed essentially to prevent protein misfolding and generation of free radicals. This warrants a system to allow for heat removal in the form of cooling as well as cleaning of metabolic wastes to prevent accumulation of toxic metabolites.

At a physiological state, the difference in arterial and venous hydrostatic and osmotic pressures allows a unidirectional flow of water and other molecules (soluble waste), with water leaving from the arterial end and molecules entering at the venous end. This simultaneous exchange of water and waste at two different ends can thus be regarded as a means of cleaning for the brain [5].

A deeper insight to this simultaneous exchange of water and waste in the blood vessels reveals the orientation of the brain vasculature, which, unlike other organs, runs in an opposite fashion, with the primary arteries lying ventral and more medially, whereas the principal veins run in a dorsal and lateral manner. Additionally, the disposition of white matter tracts creates an anisotropic field that facilitates the direction of fluid and molecules toward the main veins, which is further directed by changes in arteriovenous pressure gradients.

The paravascular system therefore maintains a very intricate and evolved system through extensive branching of vessels in the brain along with its paravascular

**Figure 6.**

*Schematic representation of the Virchow Robin spaces traveling around the blood vessels from the cisterns into the brain. Courtesy: Cherian and Beltran [1].*

system, thus following the vascular cast of the brain. This intricate system is limited by the selectively permeable capillary walls which is only large enough for a red blood cell to permeate through and may indeed be even more intricate than the vessels, since the limiting dimension of the capillaries is 3 in diameter, which is just large enough for a red blood corpuscle to squeeze through (**Figure 6**).
