RT Journal Article
T1 Chondroitin sulfate reduces cell death of rat hippocampal slices subjected to oxygen and glucose deprivation by inhibiting p38, NFκB and iNOS
A1 Martín De Saavedra Álvarez De Uribarri, María Dolores
A1 Barrio, Laura del
A1 Cañas, Noelia
A1 Egea, Javier
A1 Lorrio, Silvia
A1 Montell, Eulàlia
A1 Vergés, Josep
A1 García, Antonio
A1 López, Manuela
AB The glycosaminoglycan chondroitin sulfate (CS) is a major constituent of the extracellular matrix of the central nervous system where it can constitute part of the perineuronal nets. Constituents of the perineuronal nets are gaining interest because they have modulatory actions on their neighbouring neurons. In this study we have investigated if CS could afford protection in an acute in vitro ischemia/reoxygenation model by using isolated hippocampal slices subjected to 60 min oxygen and glucose deprivation (OGD) followed by 120 min reoxygenation (OGD/Reox). In this toxicity model, CS afforded protection of rat hippocampal slices measured as a reduction of lactate dehydrogenase (LDH) release; maximum protection (70% reduction of LDH) was obtained at the concentration of 3 mM. To evaluate the intracellular signaling pathways implicated in the protective effect of CS, we first analysed the participation of the mitogen-activated protein kinases (MAPKs) p38 and ERK1/2 by western blot. OGD/Reox induced the phosphorylation of p38 and dephosphorylation of ERK1/2; however, CS only inhibited p38 but had no effect on ERK1/2. Furthermore, OGD/Reox-induced translocation of p65 to the nucleus was prevented in CS treated hippocampal slices. Finally, CS inhibited iNOS induction caused by OGD/Reox and thereby nitric oxide (NO) production measured as a reduction in DAF-2 DA fluorescence. In conclusion, the protective effect of CS in hippocampal slices subjected to OGD/Reox can be related to a modulatory action of the local immune response by a mechanism that implies inhibition of p38, NFκB, iNOS and the production of NO.
PB Elsevier
SN 0197-0186
YR 2011
FD 2011
LK https://hdl.handle.net/20.500.14352/93461
UL https://hdl.handle.net/20.500.14352/93461
LA eng
NO Martín-de-Saavedra MD, Del Barrio L, Cañas N, Egea J, Lorrio S, Montell E, et al. Chondroitin sulfate reduces cell death of rat hippocampal slices subjected to oxygen and glucose deprivation by inhibiting p38, NFκB and iNOS. Neurochemistry International 2011;58:676–83. https://doi.org/10.1016/j.neuint.2011.02.006.
NO Universidad Autónoma de Madrid
NO Minsterio de Ciencia, Innovación y Universidades (España)
NO Ministerio de Sanidad (España)
NO Comunidad  de Madrid
NO Instituto de Salud Carlos III
NO Agencia Laín Entralgo
DS Docta Complutense
RD 6 abr 2025