Apoptosis is not an invariable component of in vitro models of cortical cerebral ischaemia

Apoptosis is not an invariable component of in vitro models of cortical cerebral ischaemia

Paul Alexander JONES;Gillian Ruth MAY;Joyce Ann MCLUCKIE;Akinori IWASHITA;John SHARKEY

【期刊名称】《细胞研究（英文版）》 【年(卷),期】2004(014)003

【摘要】Characterising the mechanisms of cell death following focal cerebral ischaemia has been hampered by a lack of an in vitro assay emulating both the apoptotic and necrotic features observed in vivo. The present study systematically characterised oxygen-glucose-deprivation (OGD) in primary rat cortical neurones to establish a reproducible model with components of both cell-death endpoints. OGD induced a time-dependent reduction in cell viability, with 80% cell death occurring 24 h after 3 h exposure to 0% O2 and 0.5 mM glucose. Indicative of a necrotic component to OGDinduced cell death, N-methyl-D-aspartate

(NMDA)

receptor

inhibition

with

MK-801

attenuated neuronal loss by 60%.The lack of protection by the caspase inhibitors DEVD-CHO and z-VAD-fmk suggested that under these conditions neurones did not die by an apoptotic mechanism. Moderating the severity of the insult by decreasing OGD exposure to 60 min did not reduce the amount of necrosis, but did induce a small degree of apoptosis (a slight reduction in cell death was observed in the