Brain ischemic preconditioning is abolished by antioxidant drugs but does not up-regulate superoxide dismutase and glutathion peroxidase.
The present work examined the hypothesis that brain ischemic tolerance induced by ischemic preconditioning (IPC) is triggered by an initial oxidative stress and is associated with an increase in antioxidant enzyme activities as one end-effector of the neuroprotection. Wistar rats were preconditioned by a single 3-min occlusion of the middle cerebral artery. After a various duration of reperfusion (30 min, 24, 72 or 168 h), rats were subjected to a 60-min focal ischemia and sacrificed 24 h later. Cerebral infarcts were significantly reduced when performed during the 24- to 72-h time window after IPC. The pretreatment with the protein synthesis inhibitor, cycloheximide (1 mg/kg, i.p., 30 min prior to IPC), completely suppressed the neuroprotection. The free radical scavenger, dimethylthiourea (DMTU; 300 mg/kg, i.p., 30 min prior to IPC) and the antioxidant ebselen (10 mg/kg, oral cramming, 2 h before and 12 h after IPC) also abolished the IPC-induced protection of the brain. Nevertheless, IPC did not induce any delayed changes in antioxidant enzyme (superoxide dismutase, glutathion peroxidase) activities nor in the neuronal expression of Mn and Cu/Zn superoxide dismutase. These results indicate that an initial oxidative stress could be involved as a trigger of IPC, while antioxidant enzymes do not play a key role as end-effectors in such a neuroprotection.
Puisieux
François
F
EA 1046, Laboratoire de Pharmacologie, Faculté de Médecine, 59045 Lille cedex, France.
Deplanque
Dominique
D
Bulckaen
Hélène
H
Maboudou
Patrice
P
Gelé
Patrick
P
Lhermitte
Michel
M
Lebuffe
Gilles
G
Bordet
Régis
R
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001923:Brain Chemistry / Q000187:drug effects; D020520:Brain Infarction / Q000517:prevention & control; D002545:Brain Ischemia / Q000201:enzymology / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D003513:Cycloheximide / Q000627:therapeutic use; D004195:Disease Models, Animal; D004347:Drug Interactions; D005979:Glutathione Peroxidase / Q000378:metabolism*; D019194:Ischemic Preconditioning; D008297:Male; D011500:Protein Synthesis Inhibitors / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion / Q000379:methods; D013482:Superoxide Dismutase / Q000378:metabolism*; D013997:Time Factors
D000975:Antioxidants; D011500:Protein Synthesis Inhibitors; D003513:Cycloheximide; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase