Effects 3-aminobenzamide on ultrastructure of hippocampal CA1 layer after global ischemia in gerbils.
Poly(ADP-ribose) polymerase (PARP EC 2.4.2.30) is a key enzyme in the DNA repair machinery, but its excessive stimulation during reperfusion after ischemia could play a critical role in cell death. Our previous study indicated that the PARP inhibitor 3-aminobenzamide (3-AB) significantly protected neuronal cells against death after a short ischemic insult. In this study we investigated the effect of 3-AB on the ischemia-evoked alterations in intracellular organelles. Gerbils were submitted to 3 min of transient forebrain ischemia followed by reinstitution of recirculation for 1-7 days. Electron microscopy showed only the signs of necrotic cell death after ischemia-reperfusion. The examination of specimens revealed a pronounced protective effect of 3-AB on the swelling of astrocytes and neurons 1 day after the ischemic insult. 3-AB also decreased the swelling of pericytes, but it had no effect on the accumulation of osmiophilic inclusions and fibril formation in astrocytes. 3-AB decreased the ischemia-induced swelling of mitochondria. The protective effects of 3-AB on cellular ultrastructure were also observed 7 days after reperfusion. These findings indicate that the inhibition of PARP may have a protective effect on cell swelling and on the state of intracellular organelles after a short-term ischemic episode.
Strosznajder
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RP
Department of Respiratory Research, Medical Research Center, Polish Academy of Sciences, Warsa, Poland. roberts@cmdik.pan.pl
Walski
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D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D002545:Brain Ischemia / Q000201:enzymology / Q000473:pathology*; D005849:Gerbillinae; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects* / Q000648:ultrastructure*; D009457:Neuroglia / Q000187:drug effects / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure; D011064:Poly Adenosine Diphosphate Ribose / Q000037:antagonists & inhibitors; D016548:Prosencephalon / Q000098:blood supply*
D001549:Benzamides; D011064:Poly Adenosine Diphosphate Ribose; C025160:3-aminobenzamide