1.Combined ampakine and BDNF treatments enhance poststroke functional recovery in aged mice via AKT-CREB signaling.
Clarkson AN1, Parker K2, Nilsson M3, Walker FR3, Gowing EK2. J Cereb Blood Flow Metab. 2015 Aug;35(8):1272-9. doi: 10.1038/jcbfm.2015.33. Epub 2015 Mar 11.
Cerebral ischemia results in damage to neuronal circuits and lasting impairment in function. We have previously reported that stimulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors with the ampakine, CX1837, increases brain-derived neurotrophic factor (BDNF) levels and affords significant motor recovery after stroke in young mice. Here, we investigated whether administration of CX1837 in aged (24 months old) mice was equally effective. In a model of focal ischemia, administration of CX1837 from 5 days after stroke resulted in a small gain of motor function by week 6 after stroke. Mice that received a local delivery of BDNF via hydrogel implanted into the stroke cavity also showed a small gain of function from 4 to 6 weeks after stroke. Combining both treatments, however, resulted in a marked improvement in motor function from 2 weeks after insult. Assessment of peri-infarct tissue 2 weeks after stroke revealed a significant increase in p-AKT and p-CREB after the combined drug treatment.
2.Gateways to clinical trials.
Tomillero A1, Moral MA. Methods Find Exp Clin Pharmacol. 2008 Jun;30(5):383-408.
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