Cytotoxic edema: mechanisms of pathological cell swelling

Abstract

<jats:p>✓Cerebral edema is caused by a variety of pathological conditions that affect the brain. It is associated with two separate pathophysiological processes with distinct molecular and physiological antecedents: those related to cytotoxic (cellular) edema of neurons and astrocytes, and those related to transcapillary flux of Na<jats:sup>+</jats:sup> and other ions, water, and serum macromolecules. In this review, the authors focus exclusively on the first of these two processes. Cytotoxic edema results from unchecked or uncompensated influx of cations, mainly Na<jats:sup>+</jats:sup>, through cation channels. The authors review the different cation channels that have been implicated in the formation of cytotoxic edema of astrocytes and neurons in different pathological states. A better understanding of these molecular mechanisms holds the promise of improved treatments of cerebral edema and of the secondary injury produced by this pathological process.</jats:p>

Fixed negative charge and the Donnan effect: a description of the driving forces associated with brain tissue swelling and oedema

“…Many studies have identified and characterized ion channels (Liang et al 2007), water channels (Marmarou 2007) and the pathological responses to injury (Mongin 2007) that may contribute to cell swelling. Those studies, however, identify facilitators of oedema formation that control the rate of swelling.…”

“…One mechanism often cited is the collapse of the transmembrane electrochemical potential owing to depletion of cellular energy stores and failure of ion pumps (Liang et al 2007). However, collapse of the gradient alone would result in equilibration of ion concentrations within the intracellular and extracellular compartments, but would not result in the net uptake of water into the tissue.…”

“…Brain oedema following TBI has traditionally been subdivided into three major categories: vasogenic (Papadopoulos et al 2005), cytotoxic (Liang et al 2007) and interstitial oedema (Kawamata et al 2007) (for reviews and a historical perspective, see Klatzo 1967;Fishman 1975;Unterberg et al 2004). Indirect measures based on diffusion-weighted imaging have suggested that following TBI without blood-brain barrier (BBB) disruption or with transient BBB disruption, cytotoxic oedema is the dominant cause of persistent brain oedema (Barzo et al 1997;Marmarou et al 2006a).…”

A Longitudinal Diffusion Tensor Imaging Study Assessing White Matter Fiber Tracts after Sports-Related Concussion

“…The investigators note that the continued expression of the positive clusters is inconsistent with cytotoxic edema, which drives ionic edema and signals a premorbid cellular process leading to necrotic cell death. 78 In discussing these findings, other researchers 68 suggest the possibility that contact sport athletes represent a distinct population because of their continued exposure to subconcussive hits leading to constant WM injury and recovery cycles and therefore might present a different recovery profile from the civilian, non-contact-sport population suffering a single mTBI episode. It must be noted that at least one study on SRC 79 showed significantly higher FA, AD, and lower MD (as compared to noncontact controls) values at two time points: *81 hours (on average) and 6 months postinjury, suggesting no significant recovery in diffusion measures during that time interval.…”

Aquaporin-4 polymorphisms and brain/body weight ratio in sudden infant death syndrome (SIDS)

“…In our study population, we made the observation that cerebral edema was reported not only for SIDS infants but also for almost all non-SIDS controls, caused by a variety of either pathological or postmortem conditions. In general, there are four types of cerebral edema (vasogenic, osmotic, interstitial, and cytotoxic edema), whereas cytotoxic edema by itself does not necessarily result in brain swelling (31).…”