In conclusion, the PI-3K/Akt and MAPK cascades selectively triggered by bFGF and IGF-1 can only modestly protect neurons from being killed by the early damage inflicted by the swelling–driving water and LY2090314 fluxes and other disturbances inflicted by OGD. But OA far more effectively reduced OGD’s early lethality than the growth factors despite stimulating the same two protein kinase cascades. The reason for this large difference is likely due to OA doing more than stimulating PI-3K/Akt and MAPK cascades by producing additional protective phosphoproteins via the inhibited PP2A’s portfolio of substrates. Thus, we will have to identify the full spectrum of affected factors before we can know how OA so effectively prevents the damage inflicted on cerebral neurons during the first 2–2.5 h of OGD. Then OA could serve as the model for designing potent therapeutics for both the OGD in the stroked brain and maybe even the ischemic heart.
Acknowledgments
We wish to thank Debbie Callaghan, Mellisa Hewitt and Amal Rashid for the primary cortical neuron cultures and Dominique Maisonneuve for technical assistance.
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The tooth sections were examined
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