Chemical preconditioning with 3-nitropropionic acid: lack of induction of neuronal tolerance in gerbil hippocampus subjected to transient forebrain ischemia.
Chemical preconditioning using the mitochondrial toxin, 3-nitropropionic acid (3-NP) has been reported to induce neuroprotection against subsequent global ischemia. To investigate the underlying mechanisms, Mongolian gerbils were pretreated with either vehicle or 3-NP at the dose of 3 or 10 mg/kg, intraperitoneal, 3 days prior to a 5-min bilateral carotid artery occlusion followed by either 48 h or 7 days of blood recirculation. Neuronal damage was assessed by a cresyl violet/fuchsin acid staining. Induction of heat shock protein 72 (HSP72) and manganese superoxide dismutase (MnSOD) expression was evaluated by Western blotting. Astroglial and microglial activation was detected by immunohistochemistry (glial fibrillary acid protein) and by histochemistry (isolectin B4 staining), respectively. Present data show that the hippocampal neuronal damage induced by ischemia were of similar extent between the vehicle- and 3-NP-treated gerbils, whatever the dose tested, indicating that 3-NP did not induce tolerance to transient forebrain ischemia under our experimental conditions. The lack of difference in the post-ischemic level of HSP72 and MnSOD protein expression and in the intensity of astroglial and microglial activation represents further indirect indications of the absence of 3-NP preconditioning effect. In conclusion, although chemical preconditioning with 3-NP is a well-established phenomenon at least in vitro and in models of focal ischemia, the relevance of 3-NP as a preconditioning molecule towards global brain ischemia remains an open question.
Unité de Biochimie, Pharmacologie, Toxicologie, Laboratoire de Pharmacodynamie, Dijon, France.
P
P
Garnier
N
N
Bertrand
C
C
Demougeot
A
A
Prigent-Tessier
C
C
Marie
A
A
Beley
D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D001253:Astrocytes / Q000737:chemistry; D015153:Blotting, Western; D003292:Convulsants / Q000494:pharmacology*; D005849:Gerbillinae; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000032:analysis; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology*; D002546:Ischemic Attack, Transient / Q000378:metabolism / Q000503:physiopathology*; D019194:Ischemic Preconditioning; D037102:Lectins; D008297:Male; D017628:Microglia / Q000737:chemistry; D009474:Neurons / Q000737:chemistry / Q000201:enzymology; D009574:Nitro Compounds; D011422:Propionates / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000032:analysis
D003292:Convulsants; D005904:Glial Fibrillary Acidic Protein; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D037102:Lectins; D009574:Nitro Compounds; D011422:Propionates; D013482:Superoxide Dismutase; C015392:3-nitropropionic acid