S100β 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 S100β concentration in serum or cerebrospinal fluid may predict lesion outcome and prognosis. The relation of S100β 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 μM kainate followed by washout. While the lower kainate concentration did not evoke neuronal loss or S100β increase, the larger concentration elicited 40% neuronal death, no change in glial number and a delayed, significant rise in extracellular S100β that peaked at 24 h. This increase was associated with a stronger expression of the S100β protein as indicated by western blotting and immunohistochemistry. Application of the microtubule disrupting agent colchicine did not change the rise in S100β induced by kainate, an effect blocked by the glutamate receptor antagonists CNQX and APV. Our data suggest that excitotoxicity was followed by release of S100β perhaps from a readily releasable pool through a mechanism independent of microtubule assembly. The raised extracellular level of S100β 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. Excitotoxicity is a major mechanism responsible for neuronal death following acute spinal cord injury. The calcium-binding protein S100β is released by astrocytes into the extracellular compartment during the first 24 h after the initial insult and represents a useful biomarker of lesion progression as its level is related to the occurrence and severity of neuronal loss. Excitotoxicity is a major mechanism responsible for neuronal death following acute spinal cord injury. The calcium-binding protein S100β is released by astrocytes into the extracellular compartment during the first 24 h after the initial insult and represents a useful biomarker of lesion progression as its level is related to the occurrence and severity of neuronal loss. © 2014 International Society for Neurochemistry.
|Titolo:||S100β as an early biomarker of excitotoxic damage in spinal cord organotypic cultures|
|Autori:||Mazzone G. L.; Nistri A.|
|Rivista:||JOURNAL OF NEUROCHEMISTRY|
|Data di pubblicazione:||2014|
|Digital Object Identifier (DOI):||10.1111/jnc.12748|
|Appare nelle tipologie:||1.1 Journal article|