During ischemia adenosine increases in the extracellular milieu. Adenosine A2A receptor expression increases on neurons and microglial cells of striatum and cortex after focal ischemia induced by medial cerebral artery occlusion (MCAo). In this model in the rat, the selective A2A antagonist, 7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazole-[4,3-e]-1,2,4-triazolo[1,5-c] pyrimidine (SCH58261) (administered 0.01 mg/Kg i.p. 5 min after ischemia) reduces glutamate outflow in the first hrs after ischemia. SCH58261 (subchronically administered after ischemia) protects from neurological deficit, cortical and striatal damage and from myelin disorganization assessed by MAG staining 24 hrs after ischemia. 24 hrs after MCAo, microglia is reactive and oligodendrocytes are clearly stained by OLIG2 antibodies. The A2A antagonist significantly reduces activation of p38 mitogen-activated protein kinase (MAPK) in microglial cells and reduces activation of JNK MAPK in oligodendrocytes (Melani et al. Brain 132:1480-95, 2009. In the acute ischemia model of oxygen and glucose deprivation (OGD) in hippocampal slices, the selective adenosine A2A receptor antagonist 4-2-[7-amino-2- (2-furyl)[1,2,4]triazolo-[2,3-a][1,3,5]triazin-5-yl-amino]ethyl phenol (ZM 241385, 100–500 nM, n=32) significantly prevents or delays anoxic depolarization (AD) appearance and protects against the loss of fEPSP induced by seven min OGD. Moreover it significantly reduces CA1 pyramidal neuronal damage as assessed by cell staining with propidium iodide (5 μg/ml) 3 hrs after the end of OGD. Results indicate that reduced excitoxity in the first hrs after ischemia, delay of AD propagation in the penumbral areas, reduced activation of p38 and JNK MAPK underlie protection by A2A antagonism.

Adenosine A2A antagonists are protective in in vivo and in vitro models of brain ischemia / Pedata F.; Melani A.; Cipriani S.; Pugliese A.M.; Traini C.; Corti F.; Giovannini MG.. - In: PURINERGIC SIGNALLING. - ISSN 1573-9538. - ELETTRONICO. - 6 (Suppl. 1):(2010), pp. S20-S21. (Intervento presentato al convegno Purines 2010 tenutosi a Tarragona- Barcelona (Spain) nel May 30th-June 2nd) [10.1007/s11302-010-9187-6].

Adenosine A2A antagonists are protective in in vivo and in vitro models of brain ischemia.

PEDATA, FELICITA;MELANI, ALESSIA;PUGLIESE, ANNA MARIA;TRAINI, CHIARA;CORTI, FRANCESCA;GIOVANNINI, MARIA GRAZIA
2010

Abstract

During ischemia adenosine increases in the extracellular milieu. Adenosine A2A receptor expression increases on neurons and microglial cells of striatum and cortex after focal ischemia induced by medial cerebral artery occlusion (MCAo). In this model in the rat, the selective A2A antagonist, 7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazole-[4,3-e]-1,2,4-triazolo[1,5-c] pyrimidine (SCH58261) (administered 0.01 mg/Kg i.p. 5 min after ischemia) reduces glutamate outflow in the first hrs after ischemia. SCH58261 (subchronically administered after ischemia) protects from neurological deficit, cortical and striatal damage and from myelin disorganization assessed by MAG staining 24 hrs after ischemia. 24 hrs after MCAo, microglia is reactive and oligodendrocytes are clearly stained by OLIG2 antibodies. The A2A antagonist significantly reduces activation of p38 mitogen-activated protein kinase (MAPK) in microglial cells and reduces activation of JNK MAPK in oligodendrocytes (Melani et al. Brain 132:1480-95, 2009. In the acute ischemia model of oxygen and glucose deprivation (OGD) in hippocampal slices, the selective adenosine A2A receptor antagonist 4-2-[7-amino-2- (2-furyl)[1,2,4]triazolo-[2,3-a][1,3,5]triazin-5-yl-amino]ethyl phenol (ZM 241385, 100–500 nM, n=32) significantly prevents or delays anoxic depolarization (AD) appearance and protects against the loss of fEPSP induced by seven min OGD. Moreover it significantly reduces CA1 pyramidal neuronal damage as assessed by cell staining with propidium iodide (5 μg/ml) 3 hrs after the end of OGD. Results indicate that reduced excitoxity in the first hrs after ischemia, delay of AD propagation in the penumbral areas, reduced activation of p38 and JNK MAPK underlie protection by A2A antagonism.
2010
Pedata F.; Melani A.; Cipriani S.; Pugliese A.M.; Traini C.; Corti F.; Giovannini MG.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/653823
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? 0
social impact