Role of PTEN nuclear translocation in excitotoxic and ischemic neuronal injuries following stroke

Stroke is a leading cause of death and disability in developed countries. About 87% of stroke cases results from blood vessel(s) occlusion in the brain, leading to neuronal death and neurological impairment (Lloyd-Jones et al., 2010). The ischemic progression likely involves multiple events, and increasing evidence showed that the ischemic neuronal death is caused, at least in part, by over-activation of N-methyl-Daspartate subtype glutamate receptors (NMDARs) (Rothman, 1983, Rothman, 1984, Simon et al., 1984). A large number of pre-clinical studies showed that NMDAR antagonists have strong neuroprotective effects against ischemic insults (Park et al., 1988b, Bullock et al., 1990). However, none of the following human clinical trials have succeeded yet (Muir, 2006). Several explanations have been suggested (Gladstone et al., 2002), including the following two major reasons that may be overcome by the novel therapeutics proposed here. First, the stroke patient inclusion periods (>6 hours) used by most clinical trials are beyond the therapeutic time window (