Disturbed Red Blood Cell Structure and Function: An Exploration of the Role of Red Blood Cells in Neurodegeneration

Abstract

The structure of red blood cells is affected by many inborn and acquired factors, but in most cases this does not seem to affect their function or survival in physiological conditions. Often, functional deficits become apparent only when they are subjected to biochemical or mechanical stress in vitro, or to pathological conditions in vivo. Our data on the misshapen red blood cells of patients with neuroacanthocytosis illustrate this general mechanism: an abnormal morphology is associated with an increase in the susceptibility of red blood cells to osmotic and mechanical stress, and alters their rheological properties. The underlying mutations may not only affect red cell function, but also render neurons in specific brain areas more susceptible to a concomitant reduction in oxygen supply. Through this mechanism, an increased susceptibility of already compromised red blood cells to physiological stress conditions may constitute an additional risk factor in vulnerable individuals. Also, susceptibility may be induced or enhanced by systemic pathological conditions such as inflammation. An exploration of the literature suggests that disturbed red blood cell function may play a role in the pathophysiology of various neurodegenerative diseases. Therefore, interventions that reduce the susceptibility of red blood cells to physiological and pathological stress may reduce the extent or progress of neurodegeneration.

Assessment of transient changes in oxygen diffusion of single red blood cells using a microfluidic analytical platform

“…Apart from the assessment of stored blood, we envision our proposed D50 metric to be used clinically to complement the existing measure of P50 in disease diagnosis, monitoring, or even intervention 1 . This may be especially pertinent in diseases associated with altered hemoglobin (such as sickle cell anemia 68 and beta thalassemia 69 ) or impaired perfusion (such as diabetic microangiopathies 70 and neurodegeneration 71 ). It is of note that our proposed D50 metric, similar to the conventional P50, does not consider the effects of RBC perfusion on the overarching tissue oxygenation efficacy.…”

The Mystery of Red Blood Cells Extracellular Vesicles in Sleep Apnea with Metabolic Dysfunction

“…Erythrocytes are involved in the regulation of the cardiovascular system via mechanisms that include their interaction with the endothelium, and these mechanisms which include the export of NO-like bioactivity, and ATP exert important cardiovascular effects [ 54 , 55 ]. The gas transportation capacity of RBCs is not only determined by the characteristics of hemoglobin but also by the capacity to regulate intracellular pH, ATP production, redox status, resistance to osmotic and mechanical stress, and recognition and removal by the immune system [ 56 ].…”

The impact of circulation in a heart–lung machine on function and survival characteristics of red blood cells

“…Maintenance of oxygen supply by extracorporeal circulation (EC) creates various nonphysiological conditions that contribute to postoperative complications such as thrombosis, intravascular hemolysis, and inflammation 1‐3 . These complications affect oxygen delivery, 4 induce anemia, 3,5 and may contribute to short‐term as well as long‐term defects in hemostasis 3,4 and to various neurological problems 5,6 . Changes in red blood cell (RBC) function and homeostasis are likely to contribute to these symptoms.…”

“…to various neurological problems. 5,6 Changes in red blood cell (RBC) function and homeostasis are likely to contribute to these symptoms. During EC, the RBCs experience mechanical stress induced by the tubing material, the pump and the oxygenator, which may lead to changes in deformability, membrane composition, and organization that affect tissue oxygenation and promote inflammation and coagulation.…”