Gary K. Steinberg, MD, PhD

Publication Details

  • Lithium treatment reduces brain injury induced by focal ischemia with partial reperfusion and the protective mechanisms dispute the importance of akt activity. Aging and disease Takahashi, T., Steinberg, G. K., Zhao, H. 2012; 3 (3): 226-233

    Abstract:

    Lithium is a mood stabilizer shown to have neuroprotective effects against several chronic and acute neuronal injuries, including stroke. However, it is unknown whether lithium treatment protects against brain injury post-stroke in a rat model of permanent distal middle cerebral artery occlusion (MCAo) combined with transient bilateral common carotid artery occlusion (CCAo), a model that mimics human stroke with partial reperfusion. In addition, whether lithium treatment alters Akt activity as measured by the kinase activity assay has not been reported, although it is known to inhibit GSK3? activity. After stroke, Akt activity contributes to neuronal survival while GSK3? activity causes neuronal death. We report that a bolus of lithium injection at stroke onset robustly reduced infarct size measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining at 48 h post-stroke and inhibited cell death in the ischemic penumbra, but not in the ischemic core, as shown by TUNEL staining performed 24 h post-stroke. However, lithium treatment did not alter the reduction in Akt activity as measured by Akt kinase assay. We further showed that lithium did not alter phosphorylated GSK3? protein levels, or the degradation of ?-catenin, a substrate of GSK3?, which is consistent with previous findings that long-term treatment is required for lithium to alter GSK3? phosphorylation. In summary, we show innovative data that lithium protects against stroke in a focal ischemia model with partial reperfusion, however, our results dispute the importance of Akt activity in the protective effects of lithium.

    View details for PubMedID 22724081

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