Mechanisms of spreading depolarization in vertebrate and insect central nervous systems

Abstract

Spreading depolarization (SD) is generated in the central nervous systems of both vertebrates and invertebrates. SD manifests as a propagating wave of electrical depression caused by a massive redistribution of ions. Mammalian SD underlies a continuum of human pathologies from migraine to stroke damage, whereas insect SD is associated with environmental stress-induced neural shutdown. The general cellular mechanisms underlying SD seem to be evolutionarily conserved throughout the animal kingdom. In particular, SD in the central nervous system of Locusta migratoria and Drosophila melanogaster has all the hallmarks of mammalian SD. Locust SD is easily induced and monitored within the metathoracic ganglion (MTG) and can be modulated both pharmacologically and by preconditioning treatments. The finding that the fly brain supports repetitive waves of SD is relatively recent but noteworthy, since it provides a genetically tractable model system. Due to the human suffering caused by SD manifestations, elucidating control mechanisms that could ultimately attenuate brain susceptibility is essential. Here we review mechanisms of SD focusing on the similarities between mammalian and insect systems. Additionally we discuss advantages of using invertebrate model systems and propose insect SD as a valuable model for providing new insights to mammalian SD.

Spreading depolarization and repolarization during cardiac arrest as an ultra-early marker of neurological recovery in a preclinical model

“…70,71 Indeed, multiple studies have shown beneficial properties of SD, including preconditioning, upregulation of growth factors, and neurogenesisis. [72][73][74][75][76][77] In addition, previous studies in insects [78][79][80][81] and rodents 72,73,82,83 suggest that SD may play a neuroprotective role during ischemia. 1,84 It is possible that this protection is enabled by a "neuronal silencing" mechanism associated with SD 85 wherein metabolism is quickly shut down, possibly to conserve residual energy and minimize production of reactive oxygen species, potentially leading to an improved survival and outcome in reversible processes.…”

A new direction for spreading depolarization: Investigation in the fly brain

“…The weight of evidence, described in an accompanying review, 6 supports a conclusion that the neural mechanisms underlying SD in flies and mammals have a common molecular basis as a result of evolutionary conservation. For example, ouabain also induces SD in the mammalian brain.…”

A Kirchhoff-Nernst-Planck framework for modeling large scale extracellular electrodiffusion surrounding morphologically detailed neurons

“…Clearly, this is would not 494 apply to most biological scenarios, which means that the results obtained with the 3-D implementation 495 are generally more reliable. In contrast to the 1-D model, the 3-D model predicts how ion concentrations 496 vary in the direction laterally from the neuronal sources, and can therefore be applied to new biological 497 problems such as spreading depression, which is associated with massive redistribution of ions that 498 spreads laterally in the cortex [3,7,54]. 499 The diffusion potentials addressed by the KNP-scheme are those that arise due to ECS concentration 500 gradients on relatively large spatial scales.…”