**4. Cardiopulmonary regulation of the CSF flow**

The primary CSF delivery mechanism, from the subarachnoid space into the paravascular system and along the paravascular space, appears to be arterial pulsatility [6, 13], coupled with brain compliance [2] (**Figure 7**). Arterial pulsatility, coupled with a perivascular compliance, generates successive physical brain compression and expansion, allowing the brain to act like a sponge by virtue of the cycle-dependent systolic-diastolic circulatory movement of blood through

**211**

**and cooling**

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

the brain [14]. This reciprocal movement influences the flow of fluids in the brain parenchyma to initiate a "pumping" effect of CSF around the vessels. These movements are driven by physiological oscillations of arterial and venous blood during craniospinal blood circulation, which are influenced by respiration, body activity,

*Graphical representation of pulsations in the artery and veins being the driving force to the CSF in the* 

Loss of arterial elasticity may lead to an impairment of this "pumping" effect in the paravascular system. This is classically seen in small vessel disease or as a consequence of low craniospinal compliance that impedes the expansion of the arteries, as can be seen in normal pressure hydrocephalus, gliosis [15], or post-traumatic hypertension. This would result in a decrease of CSF turnover that hinders the clearance of metabolites [16] and generates excess metabolic heat, thereby contrib-

Aging is a phenomenon that leads to a decline in the exchange efficiency between CSF in the paravascular spaces, and ISF occurs. This can be related to a reduction in the vessel wall pulsatility of intracortical arterioles and the widespread loss of perivascular AQP4 channels [17]. This "hardening" of vessel walls, as a consequence of aging, decreases the drainage of amyloid peptides, which may deposit in the paravascular pathways as cerebral amyloid angiopathy (CAA). These deposits further impede the drainage of ISF along the paravascular spaces, resulting in loss of homeostasis of the neuronal environment that may contribute to neuronal malfunction [15, 18]. The concurrent loss of localized thermal regulation by the paravascular pathway may add to the cascade of damage by modification of proteinaceous components, which are very sensitive to subtle changes in temperature. These structural changes in molecular geometries might disturb solubility and thus

the drainage of this metabolic waste, giving rise to a vicious circle.

**5. Alterations in the glymphatic system: impaired brain cleaning** 

lying condition of the aging human brain [19], which has also been related to various CNS disorders, such as neurodegenerative disorders that are brought on by the accumulation of misfolded, prion-like proteins (e.g., Alzheimer's or amyloid angiopathy) [17, 20, 21], normal pressure hydrocephalus [19, 22, 23], post-traumatic encephalopathy [24, 25], or neuroinflammatory disorders, such as multiple sclerosis. Furthermore, the presence of the paravascular system would explain the

The functional impairment of the paravascular system appears to be an under-

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

uting to the pathogenesis of neurological diseases.

and posture [7].

*paravascular pathway.*

**Figure 7.**

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

**Figure 7.**

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

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

*Schematic representation of the Virchow Robin spaces traveling around the blood vessels from the cisterns into* 

The arteriovenous pressure difference described above can lead to the potential role of breathing on the dynamics of CSF flow within the extensive paravascular system. The close relationship of the paranasal sinuses with the basal cisterns provides an excellent radiation chamber that can help in buffering the thermal environment of the brain through continuous evaporation of the mucosa-lined sinus surfaces in contact with the external atmosphere, hence the hypothesis of breathing playing an important role in the cooling of the brain and possibly the clearance of

Attributed to the expression and function of the AQP-4 channels, the brain cleaning mechanism is predominant during sleep. Sleep increases the expansion of the extracellular spaces by up to 60% which allows for a maximal exchange of substances to and fro the CSF and the ISF compartments [11]. This phenomenon is particularly observed in the lateral position [12]. Therefore, the restorative properties of sleep may be linked to increased glymphatic clearance of the metabolic waste products that are generated by neural activity in the awake brain. This might underpin the beneficial effects of sleep, in clearance of metabolic byproducts, the

The primary CSF delivery mechanism, from the subarachnoid space into the paravascular system and along the paravascular space, appears to be arterial pulsatility [6, 13], coupled with brain compliance [2] (**Figure 7**). Arterial pulsatility, coupled with a perivascular compliance, generates successive physical brain compression and expansion, allowing the brain to act like a sponge by virtue of the cycle-dependent systolic-diastolic circulatory movement of blood through

large enough for a red blood corpuscle to squeeze through (**Figure 6**).

**3.3 Role of breathing in brain cooling**

*the brain. Courtesy: Cherian and Beltran [1].*

**Figure 6.**

molecules within the paravascular system.

**3.4 Sleep and aquaporin-4 in brain cleaning**

phenomenon of jetlag, and the problems with lack of sleep.

**4. Cardiopulmonary regulation of the CSF flow**

**210**

*Graphical representation of pulsations in the artery and veins being the driving force to the CSF in the paravascular pathway.*

the brain [14]. This reciprocal movement influences the flow of fluids in the brain parenchyma to initiate a "pumping" effect of CSF around the vessels. These movements are driven by physiological oscillations of arterial and venous blood during craniospinal blood circulation, which are influenced by respiration, body activity, and posture [7].

Loss of arterial elasticity may lead to an impairment of this "pumping" effect in the paravascular system. This is classically seen in small vessel disease or as a consequence of low craniospinal compliance that impedes the expansion of the arteries, as can be seen in normal pressure hydrocephalus, gliosis [15], or post-traumatic hypertension. This would result in a decrease of CSF turnover that hinders the clearance of metabolites [16] and generates excess metabolic heat, thereby contributing to the pathogenesis of neurological diseases.

Aging is a phenomenon that leads to a decline in the exchange efficiency between CSF in the paravascular spaces, and ISF occurs. This can be related to a reduction in the vessel wall pulsatility of intracortical arterioles and the widespread loss of perivascular AQP4 channels [17]. This "hardening" of vessel walls, as a consequence of aging, decreases the drainage of amyloid peptides, which may deposit in the paravascular pathways as cerebral amyloid angiopathy (CAA). These deposits further impede the drainage of ISF along the paravascular spaces, resulting in loss of homeostasis of the neuronal environment that may contribute to neuronal malfunction [15, 18]. The concurrent loss of localized thermal regulation by the paravascular pathway may add to the cascade of damage by modification of proteinaceous components, which are very sensitive to subtle changes in temperature. These structural changes in molecular geometries might disturb solubility and thus the drainage of this metabolic waste, giving rise to a vicious circle.
