Glucose-induced neuroprotection through cell death mode switch
Ryousuke Fujita, Mikio Rikumaru and Hiroshi Ueda
Ischemia and/or metabolic impairment accompany traumatic brain injury in animals and humans. The ischemic area can be divided into ischemic core and so-called penumbra. In the core there is a rapid necrotic cell death, whereas in the penumbra neuronal damage develops more slowly, and followed by apoptotic cell death. Here we show the high-glucose induced neuroprotection through cell death mode switch from necrosis to apoptosis in vitro and in vivo. In cultured cortical neurons, the high-glucose treatment increased Bax expression and induces mitochondrial cytochrome c release. On the other hands, the high-glucose treatment alleviated the decrease in ATP levels through caspase-mediated poly(ADP-ribose) polymerase cleavage. Moreover, the retinal ischemia caused a marked cell death by 50% each of ganglion cell layer (GCL), inner nuclear layer (INL) and outer nuclear layer (ONL) 7 days after the ischemic treatment. The glucose (15mg/eye) injection of vitreous body completely protected the retinal cell death when it was given 30 min before or 24 h after the ischemic treatment. The action was more specific for the necrotic cell death. Thus, these results suggest that the ability to switch from necrosis to apoptosis using high-glucose treatment might make a valuable contribution to reducing cell death following traumatic or ischemic injury.