Inhibition of SDF-1 alpha further impairs diabetic wound healing. (J Vase Surg 2011;53:774-84.)”
“Kainate-mediated excitotoxicity of organotypic spinal cord cultures is an in vitro model advantageous to

investigate basic mechanisms Hippo pathway inhibitor of acute spinal injury and its pharmacological neuroprotection. Using such cultures, the putative neuroprotective agent riluzole applied at 5 mu M (plasma therapeutic concentration) was studied for its ability to prevent neurotoxicity evoked by 1 h administration of kainate. We monitored real-time release of glutamate, release of lactate dehydrogenase (LDH) (cell damage marker), occurrence of cell pyknosis, the number of surviving neurons and motoneurons, and cell culture

selleck chemicals llc metabolic activity. Co-applied riluzole strongly blocked the kainate-evoked early rise in extracellular glutamate (via calcium dependent or independent processes) and suppressed LDH release (limited to <20% of total). Although there were no significant cell losses within the first h after kainate washout, pyknosis, fewer neurons and motoneurons were observed 24 h later. MTT assay demonstrated that surviving cells were metabolically competent. Co-application of kainate and tetrodotoxin also failed to protect spinal cord slices 24 h later. When riluzole application begun at kainate washout and continued for 24 h, significant neuroprotection was observed for neurons in the central and dorsal regions, while ventral horn cells (including motoneurons) were not protected. Our data suggest that riluzole neuroprotection against excitotoxicity was feasible, although it paradoxically required delayed drug administration, and was not extended to the ventral horn. We propose that riluzole was acting on yet-unidentified processes downstream of glutamate release and receptor

activation. Deciphering their identity and role in cell death mechanisms may be an important goal to develop neuroprotection. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Background: Recent evidence suggests that hydrogen sulfide is capable of mitigating the degree PF477736 in vitro of cellular damage associated with ischemia-reperfusion injury (IRI).

Methods: This study evaluated the potential utility of hydrogen sulfide in preventing IRI in skeletal muscle by using in vitro (cultured myotubes subjected to sequential hypoxia and normoxia) and in vivo (mouse hind limb ischemia, followed by reperfusion) models to determine whether intravenous hydrogen sulfide delivered after the ischemic event had occurred (pharmacologic postconditioning) conferred protection against IRI. Injury score and apoptotic index were determined by analysis of specimens stained with hematoxylin and eosin and terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick-end labeling, respectively.