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

Abstract:

: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.

authors

Sun MK,Hongpaisan J,Alkon DL

doi

10.1073/pnas.0907842106

subject

Has Abstract

pub_date

2009-08-25 00:00:00

pages

14676-80

issue

34

eissn

0027-8424

issn

1091-6490

pii

0907842106

journal_volume

106

pub_type

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