A mathematical model of cellular swelling in Neuromyelitis optica
Journal
Journal of Theoretical Biology
Journal Volume
433
Pages
39-48
Date Issued
2017
Author(s)
Abstract
Neuromyelitis Optica (NMO) is a severe neuro-inflammatory disease of the central nervous system characterized by predominant damage to the optic nerve and of the spinal cord. The pathogenic antibody found in the majority of patients targets the AQP4 channels on astrocytic endfeet and causes the cells to swell. Although, the pathophysiology of the disease is broadly known, there are no specific targeted treatments for this process clinically available nor accurate prognostic markers both during attacks and for predicting long term neuronal damage. This lack is, in part, due to the rarity of the disease and its relatively recent pathogenic clarity. Hence, the ability to mathematically model the progress of the condition to test prospective therapies in silico would be a step forward. This paper combines state of the art models of cellular metabolism and cytotoxic oedema in neurons and astrocytes and augments it with a detailed characterization of water transport across the cellular membrane. In particular, we capture the process of perforation of the cell through the human complement cascade and resulting water and ionic fluxes. Simulating NMO by injecting its antibody and human complement into the extracellular space showed a 25% increase of the astrocytic volume after 12 h from onset. Most of the volume change occurred during the first 30 min of simulation with a peak volume change of 38%. The model was further adapted to simulate the therapeutic potential of CD59. It was found that there is a threshold of CD59 concentration that can prevent the swelling of astrocytes. Since the astrocyte volume changes mostly during the first hour, further experimental work should focus on this time scale to provide data for further model refinement and validation. ? 2017
Subjects
antibody
aquaporin 4
CD59 antigen
CD59 protein, human
water
metabolism
neurology
numerical model
pathogen
reaction kinetics
Article
astrocyte
cell membrane
cell metabolism
cell swelling
cell volume
complement system
computer model
controlled study
cytotoxicity
extracellular space
human
ion transport
mathematical model
myelooptic neuropathy
nerve cell
nonhuman
pathogenesis
priority journal
time factor
water transport
animal
brain edema
cell size
computer simulation
drug effect
pathology
theoretical model
Animals
Astrocytes
Brain Edema
CD59 Antigens
Cell Membrane
Cell Size
Computer Simulation
Humans
Models, Theoretical
Neuromyelitis Optica
Water
Type
journal article