Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/102205
Title: Diazoxide enhances excitotoxicity-induced neurogenesis and attenuates neurodegeneration in the rat non-neurogenic hippocampus
Author: Martínez-Moreno, M.
Batlle, M.
Ortega, Francisco J.
Gimeno-Bayón, J.
Andrade, C.
Mahy Gehenne, Josette Nicole
Rodríguez Allué, Manuel José
Keywords: Micròglia
Medicaments
Regeneració del sistema nerviós
Canals de potassi
Rates
Inflamació
Microglia
Drugs
Nervous system regeneration
Potassium channels
Rats
Inflammation
Issue Date: 25-Jul-2016
Publisher: Elsevier Ltd
Abstract: Diazoxide, a well-known mitochondrial KATP channel opener with neuroprotective effects, has been proposed for the effective and safe treatment of neuroinflammation. To test whether diazoxide affects the neurogenesis associated with excitotoxicity in brain injury, we induced lesions by injecting excitotoxic N-methyl-d-aspartate (NMDA) into the rat hippocampus and analyzed the effects of a daily oral administration of diazoxide on the induced lesion. Specific glial and neuronal staining showed that NMDA elicited a strong glial reaction associated with progressive neuronal loss in the whole hippocampal formation. Doublecortin immunohistochemistry and bromo-deoxyuridine (BrdU)-NeuN double immunohistochemistry revealed that NMDA also induced cell proliferation and neurogenesis in the lesioned non-neurogenic hippocampus. Furthermore, glial fibrillary acidic protein (GFAP)-positive cells in the injured hippocampus expressed transcription factor Sp8 indicating that the excitotoxic lesion elicited the migration of progenitors from the subventricular zone and/or the reprograming of reactive astrocytes. Diazoxide treatment attenuated the NMDA-induced hippocampal injury in rats, as demonstrated by decreases in the size of the lesion, neuronal loss and microglial reaction. Diazoxide also increased the number of BrdU/NeuN double-stained cells and elevated the number of Sp8-positive cells in the lesioned hippocampus. These results indicate a role for KATP channel activation in regulating excitotoxicity-induced neurogenesis in brain injury.
Note: Versió postprint del document publicat a: http://dx.doi.org/10.1016/j.neuroscience.2016.07.032
It is part of: Neuroscience, 2016, vol. 333, p. 229-243
Related resource: http://dx.doi.org/10.1016/j.neuroscience.2016.07.032
URI: http://hdl.handle.net/2445/102205
ISSN: 0306-4522
Appears in Collections:Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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