The effects of the superoxide dismutase mimetic, MnTMPyP, post hypoxia and oxygen glucose deprivation in isolated rat hippocampal slices.

The contributions of hypoxia, oxygen glucose deprivation (OGD) and oxidative stress, to the pathophysiology of acute ischemic stroke (AIS) are well established and can lead to disruptions in synaptic signaling. Antioxidant compounds have previously been shown to have a preconditioning and neuroprotective effect against an ischemic insult. Therefore, in this study we explored the effects of the reactive oxygen species (ROS) scavenger, MnTMPyP, on synaptic transmission in two models, hypoxia and oxygen glucose deprivation (OGD), in isolated rat hippocampal slices using electrophysiological techniques and organotypic hippocampal slice cultures. We report a novel modulatory effect of MnTMPyP on synaptic transmission post hypoxia and OGD, an effect specific to the CA1 region of the hippocampus. This reduction of the fEPSP by MnTMPyP post hypoxia in the CA1 was attenuated through the co-application of the adenosine A1 receptor antagonist, DPCPX (200 nM), and the NMDA receptor antagonists, AP-5 (10 µM) and DCKA (5 µM). These effects were not observed in the OGD model. Our organotypic data demonstrated a protective role for MnTMPyP, where slices had significantly less cell death in the CA1 region post hypoxia and OGD, compared to controls. Taken together, our results suggest a complex role for MnTMPyP on both synaptic signaling in an hypoxic environment and cell viability. Whether this SOD mimetic will play an important role in ischemia still remains to be determined.