Effect of antioxidants on functional recovery after in vitro-induced ischemia and long-term potentiation recorded in the pyramidal layer of the CA1 area of rat hippocampus.
Ischemic stroke is one of the leading causes of cognitive impairment. Antioxidants may be beneficial in brain diseases in which oxidative stress can be assumed. The effect of two antioxidants, stobadine and its new derivative coded SMe1EC2, was studied on post-ischemic functional recovery in the hippocampus of young and 18-month-old rats. The synaptic transmission was apparently absent after 6-min hypoxia/hypoglycemia in both age groups. Re-oxygenation resulted in negligible functional recovery in untreated slices, yet the presence of pyridoindoles tested elicited improved recovery upon re-oxygenation. SMe1EC2 was found more effective in post-ischemic functional recovery and was further tested in the hippocampus of 15-month-old rats in long-term potentiation (LTP) experiments, a synaptic model of learning and memory mechanisms. In slices of aged rats, 3.5-min hypoxia/hypoglycemia resulted in depression of the LTP induction phase (immediately after high frequency stimulation) and this was prevented in the presence of SMe1EC2 (3 µmol/l). Upon "normoxia", marked amelioration of LTP was recorded in the presence of the antioxidant in about 1.5 order lower concentration. These results suggest a possible application of the pyridoindole in the management of brain ischemia and cognitive impairment.
Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Bratislava, Slovak Republic. zdenka.gasparova@savba.sk.
Zdenka
Z
Gasparova
Veronika
V
Stara
Svorad
S
Stolc
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism*; D002545:Brain Ischemia / Q000188:drug therapy / Q000473:pathology; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D002243:Carbolines / Q000737:chemistry; D003071:Cognition / Q000187:drug effects; D004594:Electrophysiology / Q000379:methods; D007003:Hypoglycemia / Q000378:metabolism; D000860:Hypoxia; D007511:Ischemia / Q000473:pathology*; D017774:Long-Term Potentiation; D008297:Male; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D017966:Pyramidal Cells / Q000166:cytology*; D051381:Rats; D013997:Time Factors
D000975:Antioxidants; D002243:Carbolines; D010100:Oxygen; C100106:dicarbine