S100β as an early biomarker of excitotoxic damage in spinal cord organotypic cultures

Abstract

S100b is a cytoplasmic calcium-binding protein mainly expressed by glia and considered to be a useful biomarker for brain or spinal cord injury. Indeed, clinical studies suggest that the S100b concentration in serum or cerebrospinal fluid may predict lesion outcome and prognosis. The relation of S100b levels to damage severity and its timecourse remains, however, unclear. This study used a validated in vitro model of spinal cord injury induced by kainate-mediated excitotoxicity to investigate these issues. After 22 days in vitro, rat organotypic spinal cord slices were subjected to one transient application (1 h) of 1 or 100 lM kainate followed by washout. While the lower kainate concentration did not evoke neuronal loss or S100b increase, the larger concentration elicited 40% neuronal death, no change in glial number and a delayed, significant rise in extracellular S100b that peaked at 24 h. This increase was associated with a stronger expression of the S100b protein as indicated by western blotting and immunohistochemistry. Application of the microtubule disrupting agent colchicine did not change the rise in S100b induced by kainate, an effect blocked by the glutamate receptor antagonists CNQX and APV. Our data suggest that excitotoxicity was followed by release of S100b perhaps from a readily releasable pool through a mechanism independent of microtubule assembly. The raised extracellular level of S100b appeared to reflect glial reactivity to the kainate-evoked lesion in accordance with the view that this protein may be involved in tissue protection and repair after acute injury.

Zinc Binding to S100B Affords Regulation of Trace Metal Homeostasis and Excitotoxicity in the Brain

“…This crosstalk potentially affects multiple downstream synaptic processes but also patho-physiological events such as excitotoxicity. Intriguingly, S100B concentrations have been reported high under conditions facilitating excitotoxicity (Mazzone and Nistri, 2014 ).…”

“…Thus, neural S100 proteins are increased during processes activating NF-κB, such as inflammatory processes (Donato et al, 2013 ) and other insults to the brain. In particular, release of S100B was reported in response to excitotoxicity (Mazzone and Nistri, 2014 ).…”

Water-soluble C60 fullerene ameliorates astroglial reactivity and TNFa production in retina of diabetic rats

“…Besides, overexpression of GFAP in the brain of animals with experimentally induced diabetes was demonstrated in various brain areas (Nedzvetsky et al, 2012). Various types of brain injury provoke release of S100 family proteins into cerebrospinal fluid and blood (Rothermundt et al, 2003;Michetti et al, 2012), which allows this glial marker to be used as a diagnostic tool to determine CNS damage (Gerlach et al, 2006;Ellis et al, 2007;Mazzone & Nistri, 2014). Several in vitro results have demonstrated that S100β efflux, which was stimulated with oxygen-glucose deprivation and metabolic stress, is independent of the synthesis S100β protein de novo (Davey et al, 2001;Gerlach et al, 2006;Ellis et al, 2007).…”

The Effect of Mechanical Ventilation on TASK-1 Expression in the Brain in a Rat Model

“…Finally, they proposed a hypothesis whereby TASK channel inhibition via persistent autocrine activation of the NO/cGMP/PKG cascade could sensitize NOS-expressing neurons to excitotoxic damage in brain neurodegenerative processes via a sustained increase in their excitability. Moreover, Mazzone and Nistri [39] used a validated in vitro model of spinal cord injury induced by kainate-mediated excitotoxicity to explore relation of S100B levels and damage severity and found that S100B represents a useful biomarker of lesion progression as its level is related to the occurrence and severity of neuronal loss due to excitotoxicity. Therefore, MV might cause neuronal damage directly in the brain or cause apoptosis by reducing the protective factor-TASK-1 channel expression.…”