Intracranial pressure influences the level of sympathetic tone

Abstract

Sympathetic overdrive is associated with many diseases, but its origin remains an enigma. An emerging hypothesis in the development of cardiovascular disease is that the brain puts the utmost priority on maintaining its own blood supply; even if this comes at the "cost" of high blood pressure to the rest of the body. A critical step in making a causative link between reduced brain blood flow and cardiovascular disease is how changes in cerebral perfusion affect the sympathetic nervous system. A direct link between decreases in cerebral perfusion pressure and sympathetic tone generation in a conscious large animal has not been shown. We hypothesized that there is a novel control pathway between physiological levels of intracranial pressure (ICP) and blood pressure via the sympathetic nervous system. Intracerebroventricular infusion of saline produced a ramped increase in ICP of up to 20 mmHg over a 30-minute infusion period (baseline 4.0±1.1 mmHg). The ICP increase was matched by an increase mean arterial pressure such that cerebral perfusion pressure remained constant. Direct recordings of renal sympathetic nerve activity indicated that sympathetic drive increased with increasing ICP. Ganglionic blockade, by hexamethonium, preventing sympathetic transmission, abolished the increase in arterial pressure in response to increased ICP and was associated with a significant decrease in cerebral perfusion pressure. This is the first study to show that physiological elevations in intracranial pressure regulate renal sympathetic activity in conscious animals. We have demonstrated a novel physiological mechanism linking ICP levels with sympathetic discharge via a possible novel intracranial baroreflex.

Astrocytes monitor cerebral perfusion and control systemic circulation to maintain brain blood flow

“…1e, f). These data are in agreement with the recently reported results of the experiments performed in anaesthetized mice 11 , conscious sheep 12 , and humans 11 .…”

Anatomical basis and physiological role of cerebrospinal fluid transport through the murine cribriform plate

“…CSF production is not a passive process, but rather one under active neural control (Lindvall et al, 1978; Edvinsson and Lindvall, 1978; Tuor et al, 1990). As ICP needs to be maintained within a healthy range, there are likely homeostatic processes that sense ICP, and cause compensatory increases or decreases in CSF production, similar to other mechanosensory processes in other organs of the body (Umans and Liberles, 2018; Guild et al, 2018). A potential mechanism mediating this feedback is mechanically sensitive ASIC3 channels, which are expressed in the ventricles (Jalalvand et al, 2018), and are sensitive to changes in pressure that are physiologically relevant to ICP regulation.…”

Anatomical basis and physiological role of cerebrospinal fluid transport through the murine cribriform plate

“…CSF production is not a passive process, but rather one under active neural control [80][81][82] . As ICP needs to be maintained within a healthy range, there are likely homeostatic processes that sense ICP, and cause compensatory increases or decreases in CSF production, similar to other mechanosensory processes in other organs of the body 83,84 . A potential mechanism mediating this feedback is mechanically-sensitive ASIC3 channels, which are expressed in the ventricles 85 , and are sensitive to changes in pressure that are physiologically relevant to ICP regulation.…”