Abstract
Cell volume changes are ubiquitous in normal and pathological activity of the brain. Nevertheless, we know little about the dynamics of cell and tissue swelling, and the differential changes in the volumes of neurons and glia during pathological states such as spreading depolarizations (SD) under ischemic and non–ischemic conditions, and epileptic seizures. By combining the Hodgkin–Huxley type spiking dynamics, dynamic ion concentrations, and simultaneous neuronal and astroglial volume changes into a comprehensive model, we elucidate why glial cells swell more than neurons in SD and the special case of anoxic depolarization (AD), and explore the relative contributions of the two cell types to tissue swelling. Our results demonstrate that anion channels, particularly Cl−, are intrinsically connected to cell swelling and blocking these currents prevents changes in cell volume. The model is based on a simple and physiologically realistic description. We introduce model extensions that are either derived purely from first physical principles of electroneutrality, osmosis, and conservation of particles, or by a phenomenological combination of these principles and known physiological facts. This work provides insights into numerous studies related to neuronal and glial volume changes in SD that otherwise seem contradictory, and is broadly applicable to swelling in other cell types and conditions.
Highlights
Spreading depolarization (SD) is an abrupt process of prolonged cellular depolarization, which spreads through brain tissue in a wave–like manner
We develop a new comprehensive model that takes into account the dynamics of glial, neuronal, and extracellular space (ECS) volumes simultaneously, and explains the quantative differences between glial and neuronal swelling during SD
Our model suggests that the involvement of Cl− channels in regulatory volume decrease (RVD) after SD is necessary, but not sufficient
Summary
Spreading depolarization (SD) is an abrupt process of prolonged cellular depolarization, which spreads through brain tissue in a wave–like manner. It is characterized by the breakdown of ion gradients, the depression of neuronal electrical activity, and an extreme shrinkage of extracellular space (ECS) resulting from the swelling of neurons and the surrounding glia cells [1, 2]. The cessation of electrical activity that goes along with SD is called spreading depression, but the terminology is ambiguous and many authors refer to the whole event as spreading depolarization instead. Astrocytic and Neuronal Swelling in Spreading Depolarization by extracellular K+ elevation. SD is believed to cause migraine [3,4,5,6,7,8], and there appears to be a correlation between brain susceptibilities to SD and epileptic seizures [2, 9,10,11,12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
