Postischemic PKC activation rescues retrograde and anterograde long-term memory.

نویسندگان

  • Miao-Kun Sun
  • Jarin Hongpaisan
  • Daniel L Alkon
چکیده

Therapeutics for cerebral ischemia/hypoxia, which often results in ischemic stroke in humans, are a global unmet medical need. Here, we report that bryostatin-1, a highly potent protein kinase C (PKC) activator, interrupts pathophysiological molecular cascades and apoptosis triggered by cerebral ischemia/hypoxia, enhances neurotrophic activity, and induces synaptogenesis in rats. This postischemic therapeutic approach is further shown to preserve learning and memory capacity even 4 months later as well as long-term memory induced before the ischemic event. Our results of electromicroscopic and immunohistochemical analyses of neuronal and synaptic ultra-structure are consistent with a PKC-mediated synaptic remodeling and repair process that confers long-lasting preservation of spatial learning and memory before and after the cerebral ischemic/hypoxic event, suggesting a previously undescribed therapeutic modality for cerebral ischemia/hypoxia and ischemic stroke.

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عنوان ژورنال:
  • Proceedings of the National Academy of Sciences of the United States of America

دوره 106 34  شماره 

صفحات  -

تاریخ انتشار 2009