Molecular pathophysiology of cerebral edema

Abstract

Advancements in molecular biology have led to a greater understanding of the individual proteins responsible for generating cerebral edema. In large part, the study of cerebral edema is the study of maladaptive ion transport. Following acute CNS injury, cells of the neurovascular unit, particularly brain endothelial cells and astrocytes, undergo a program of pre- and post-transcriptional changes in the activity of ion channels and transporters. These changes can result in maladaptive ion transport and the generation of abnormal osmotic forces that, ultimately, manifest as cerebral edema. This review discusses past models and current knowledge regarding the molecular and cellular pathophysiology of cerebral edema.

A Biophysical Model for Cytotoxic Cell Swelling

“…The formation of cerebral cytotoxic edema is often recognized as an important pathophysiological mechanism leading to initial neuronal damage or secondary deterioration in patients with cerebral ischemia (Stokum et al, 2016). In this population, interindividual differences with regard to the speed and degree of cytotoxic edema formation are large and not well understood (Hofmeijer et al, 2009).…”

Recent Research Trend for Ménièreʼs Disease

“…In the specimens from Meniere's disease in the present study, the tight junctions appeared to be normal, even at high magnification microscopy and also even in severely edematous BLB cytoarchitecture. In contrast, BBB in vasogenic edema appears to be associated with altered tight junction proteins, and separation noted at tight junctions; however, it is noted that these changes occur late in the course of brain injury 32 . It is possible that there is altered expression of tight junction proteins in the VEC of Meniere's disease, without structural changes that can be visualized.…”

“…The increased vesicle formation and caveolae-like formations in the VEC, with polarization to the abluminal side, which would lead one to conclude that there is increased transcytosis, possibly vesicles being used to traffic cargo across the VECs. During BBB breakdown, there is also an increase in trans-endothelial channels in VECs 32 . In the specimens from Meniere's disease in the present study, the tight junctions appeared to be normal, even at high magnification microscopy and also even in severely edematous BLB cytoarchitecture.…”

Blood–Brain Barrier Disruption, Vascular Impairment, and Ischemia/Reperfusion Damage in Diabetic Stroke

“…Vasogenic edema formation is driven by hydrostatic pressure gradient, which is influenced by intracranial pressure, systemic blood pressure, capillary occlusion, and vasospasm 19. In vasogenic edema, following TJ and BBB rupture, transendothelial permeability increases, facilitating the entry of water and plasma proteins such as albumin and immunoglobulin G into the brain interstitial space 21. The osmotic pressure gradient mediated by osmotically active molecules such as Na + and proteins also mediates water influx in vasogenic edema 19.…”

“…The interaction between the astrocytes, Aquaporin‐4, and endothelial cells regulates brain water content as well as poststroke edema resolution (ie, transport of water via bulk flow from the brain parenchyma to the vascular, intraventricular, and subarachnoid compartments) 49, 56. Aquaporin‐4 has been implicated in water uptake into the brain tissue during the evolution of cytotoxic edema, as well as in water clearance after vasogenic edema 21, 49, 57. Using astroglial conditional Aquaporin‐4 knockout mice, it has been shown that deletion of Aquaporin‐4 decreases about 30% of brain water uptake after systemic hypo‐osmotic stress without affecting BBB impermeability to macromolecules 49.…”