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Glibenclamide enhances neurogenesis and improves long-term functional recovery after transient focal cerebral ischemia

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Glibenclamide is neuroprotective against cerebral ischemia in rats. We studied whether glibenclamide enhances long-term brain repair and improves behavioral recovery after stroke. Adult male Wistar rats were subjected to transient middle cerebral artery occlusion (MCAO) for 90 minutes. A low dose of glibenclamide (total 0.6mg) was administered intravenously 6, 12, and 24 hours after reperfusion. We assessed behavioral outcome during a 30-day follow-up and animals were perfused for histological evaluation. In vitro speciﬁc binding of glibenclamide to microglia increased after pro-inﬂammatory stimuli. In vivo glibenclamide was associated with increased migration of doublecortin-positive cells in the striatum toward the ischemic lesion 72 hours after MCAO, and reactive microglia expressed sulfonylurea receptor 1 (SUR1) and Kir6.2 in the medial striatum. One month after MCAO, glibenclamide was also associated with increased number of NeuN-positive and 5-bromo-2-deoxyuridine-positive neurons in the cortex and hippocampus, and enhanced angiogenesis in the hippocampus. Consequently, glibenclamide-treated MCAO rats showed improved performance in the limb-placing test on postoperative days 22 to 29, and in the cylinder and water-maze test on postoperative day 29. Therefore, acute blockade of SUR1 by glibenclamide enhanced long-term brain repair in MCAO rats, which was associated with improved behavioral outcome.

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International Society for Cerebral Blood Flow and Metabolism

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Journal of Cerebral Blood Flow and Metabolism, 2013, vol. 33, num. 3, p. 356-364

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(c) Ortega González, Fco. Javier et al., 2013

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Articles publicats en revistes (Ciències Fisiològiques)

# metadata.dc.title[].value
Glibenclamide enhances neurogenesis and improves long-term functional recovery after transient focal cerebral ischemia