Details

Autor(en) / Beteiligte

• Ortega, F.J.
• Gimeno-Bayon, J.
• Espinosa-Parrilla, J.F.
• Carrasco, J.L.
• Batlle, M.
• Pugliese, M.
• Mahy, N.
• Rodríguez, M.J.

Titel

ATP-dependent potassium channel blockade strengthens microglial neuroprotection after hypoxia–ischemia in rats

Ist Teil von

• Experimental neurology, 2012-05, Vol.235 (1), p.282-296

Ort / Verlag

Amsterdam: Elsevier Inc

Erscheinungsjahr

2012

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• Stroke causes CNS injury associated with strong fast microglial activation as part of the inflammatory response. In rat models of stroke, sulphonylurea receptor blockade with glibenclamide reduced cerebral edema and infarct volume. We postulated that glibenclamide administered during the early stages of stroke might foster neuroprotective microglial activity through ATP-sensitive potassium (KATP) channel blockade. We found in vitro that BV2 cell line showed upregulated expression of KATP channel subunits in response to pro-inflammatory signals and that glibenclamide increases the reactive morphology of microglia, phagocytic capacity and TNFα release. Moreover, glibenclamide administered to rats 6, 12 and 24h after transient Middle Cerebral Artery occlusion improved neurological outcome and preserved neurons in the lesioned core three days after reperfusion. Immunohistochemistry with specific markers to neuron, astroglia, microglia and lymphocytes showed that resident amoeboid microglia are the main cell population in that necrotic zone. These reactive microglial cells express SUR1, SUR2B and Kir6.2 proteins that assemble in functional KATP channels. These findings provide that evidence for the key role of KATP channels in the control of microglial reactivity are consistent with a microglial effect of glibenclamide into the ischemic brain and suggest a neuroprotective role of microglia in the early stages of stroke. ► Reactive microglia express KATP channels in tMCAo rat brain. ► Glibenclamide improves neurological outcome and neuroprotection in tMCAo rats. ► Microglial activation enhances KATP channel expression in vitro. ► KATP channel blockade modulates microglial reactivity and phagocytosis in vitro. ► Glibenclamide effects in stroke therapy involve microglia-mediated neuroprotection.