Hypothesis on the Role of Cryptochromes in Inflammation and Subarachnoid Hemorrhage Outcome

Abstract

We have recently found that the temperature variability (TV) in the day–night cycle may predict the mean intracranial pressure in the following 24 h (ICP24) in subarachnoid hemorrhage (SAH) patients under multimodality monitoring, sedation, and hypothermia (<35°C). Specifically, we found that ICP24 = 6 (4 − TV) mmHg. TV is the ratio between the coefficient of variation of temperature during the nocturnal and the preceding diurnal periods. This result suggests that the circadian clock reflects brain plasticity mechanisms and its malfunctioning leads to deterioration of the neurologic status. The sleep–wake cycle is absent in these patients and their circadian clock can function properly only by environment light-independent mechanisms. One mechanism involves the circadian clock proteins named cryptochromes (CRYs). CRYs are highly preserved and widespread in the evolutionary tree, are expressed in different cell types in humans [type II CRYs, in two forms: human cryptochrome 1 and 2 (hCRY1 and hCRY2)], and in certain species, respond to blue light and play role in magnetoreception. Interestingly, SAH outcome seems to correlate with inflammation, and CRYs decrease inflammatory activity. Our hypothesis derived from these observations is that CRYs modulate the circadian oscillation of temperature even during therapeutic hypothermia and improve outcome in SAH through decrease in inflammation. A strategy to test this hypothesis is to measure periodically during the acute phase of high-grade SAH the level of CRYs in cerebrospinal fluid (CSF) and circulating white blood cells, and to correlate these levels with outcome, TV, ICP24, and pro- and anti-inflammatory markers in CSF and blood. If this hypothesis is true, the development of therapies targeting inflammation in SAH could take advantage of cryptochrome properties. It has been shown that blue light phototherapy increases the expression of CRYs in blood mononuclear cells in jaundiced neonates. Likewise, visual stimulus with flashing light improves Alzheimer’s disease features in experimental model and there is a prominent expression of CRYs in the retina. Remarkably, recent evidence showed that hCRY2 responds to electromagnetic fields, which could be one elusive mechanism of action of transcranial magnetic stimulation and a reason for its use in SAH.

Daily Meteorological Parameters Influence the Risk of Intracerebral Hemorrhage in a Subtropical Monsoon Basin Climate

“…This magnetic field can act on human cryptochrome, a molecule involved in circadian rhythms and inflammation. 32 It has been found in clinical research that two days after geomagnetic storms, the risk of myocardial infarction with ST-elevation was over 1.5 times increased in some patients. 33 …”

Quantum microRNA Assessment of COVID-19 RNA Vaccine: Hidden Potency of BNT162b2 SASR-CoV-2 Spike RNA as MicroRNA Vaccine

“…Translocator Like (ARNTL, BMAL1), Period Circadian Regulators (PERs), Cryptochrome Circadian Regulators (CRYs). Disturbance of these clock genes lead to pathophysiology for cardiovascular system, whereas the stabilization is protective [47]. Although On the contrary, CovS-miR-21 from BNT162b2 would limit innate immunity via decreasing of ARNTL in circadian-rhythm [54,55].…”

“…Subsequently, since CoVS-miR-21 was a viral pathogenic factor, adenovirus-or vaccinia virus-based DNA vaccines should consider additional side-effects of SARS-CoV-2 S-derived miRNAs as circadian rhythm disturber because SARS-CoV-2 S DNA in adenovirus vector may be integrated into the host chromosome as a character of viral vectors [6,58,59]. For example, as the relationship of subarachnoid hemorrhage to circadian oscillation via CRYs and PER2 has been widely studied [47,60,61] spontaneous brain injury may be induced by SARS-CoV-2 S-derived miRNA.…”

Healthy Aging Guided by Circadian Rhythm Monitoring Using a Smartwatch-Like Device

“…in monitors of intensive care unit (12,13). Similarly, the ratio between the mean skin temperature during sleep and the preceding wake period correlated with the probability of occurrence of seizure in the following day in epileptic children (10,11).…”

“…We previously showed that the adult human hypothalamus may participate in brain plasticity through the expression of markers related to the formation of new neurons (7)(8)(9). Next, we showed that the possible role of the hypothalamus in brain plasticity could be quantified (10)(11)(12)(13). Accordingly, the mean intracranial pressure may be predicted with 24 hours of antecedence in stroke cases by the analysis of the variability of body temperature registered Copyright © 2021, Author(s).…”