Jang-Yen Wu
Posters-Accepted Abstracts: Brain Disord Ther
Recently we have developed several novel drugs including granulocyte-colony stimulating factor (G-CSF), a stem cell
enhancer and facilitator and a neuroprotector, S-methyl-N,N-diethylthiolcarbamate sulfoxide (DETC-MeSO), a NMDA
receptor partial antagonist and sulindac, a potent catalytic anti-oxidant and anti-inflammatory agent and it was shown that
each of them is quite effective in protecting and repairing ischemia-induced neuronal injury in MCAO stroke animal model as
well as in hypoxia culture model. In addition, we found thatsimilar protection could be achieved by the multi-drug treatment
with a combination of G-CSF, DETC-MeSO, and sulindac at 1/10 of the dose of the individual drug as mentioned above. The
major findings are summarized as follows: 1. The brain infract size is reduced by 50-60% by the multi-drug treatment either
administered prior to or post MCAO surgery; 2. The anti-apoptotic protein markers such as Bcl-2 are markedly up-regulated
whereas the pro-apoptotic protein markers such as Bax, Bak, Bim, caspase 3 etc are markedly down-regulated; 3. The stress
markers for endoplasmic reticulum (ER), such as GRP78 and CHOP are greatly down-regulated. In summary, these results
indicate that the multi-drug treatment with G-CSF, DETC-MeSO and sulindac is effective in protecting and restoring the
neuronal function in MCAO stroke model and represents a new approach for clinical intervention for stroke.