The time-course of DNA fragmentation in the choroid plexus and the CA1 region following transient global ischemia in the rat brain. The effect of intra-ischemic hypothermia.
The time-course of DNA fragmentation in the CA1 region of the hippocampus and the choroid plexus was studied following induction of transient forebrain ischemia under lethal normothermic (37 degrees C), or sublethal hypothermic (33 degrees C) conditions. Oligonucleosomal- and high-molecular-weight DNA fragmentation were analysed by conventional agarose gel electrophoresis and pulsed-field gel electrophoresis, respectively. DNA breaks were visualized by the terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridinetriphosphate nick-end labeling method. At 48 h of recovery following normothermic ischemia, in situ labeling of DNA breaks were widespread in medial CA1 and high-molecular-weight DNA cleavage was seen. In contrast, at the same time-point in lateral CA1, many pyknotic but few cells displaying in situ labeling of DNA breaks were observed. Major oligonucleosomal DNA fragmentation was not seen until 72 h of recovery. Following hypothermic ischemia, DNA fragmentation was absent in CA1. DNA fragmentation was seen in the choroid plexus at 24 h of recovery following normothermic ischemia, which was diminished by 48 h of recovery. In conclusion, oligonucleosomal and high-molecular-weight DNA fragmentation at 10-50 kilobase pairs, occur in CA1 after morphological signs, and acidophilia signifying neurodegeneration appear. DNA fragmentation and cell death in the choroid plexus precede neuronal death in CA1 and may play a causative role.
Ferrand-Drake
M
M
Wallenberg Neuroscience Center, Laboratory for Experimental Brain Research, University Hospital, Lund, Sweden.
Wieloch
T
T
D000818:Animals; D001345:Autoradiography; D001923:Brain Chemistry / Q000502:physiology*; D002831:Choroid Plexus / Q000378:metabolism* / Q000503:physiopathology; D004396:Coloring Agents; D053938:DNA Fragmentation / Q000502:physiology*; D004587:Electrophoresis, Agar Gel; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D007035:Hypothermia / Q000378:metabolism* / Q000503:physiopathology; D020287:In Situ Nick-End Labeling; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000503:physiopathology; D007700:Kinetics; D008297:Male; D008970:Molecular Weight; D009707:Nucleosomes / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D004396:Coloring Agents; D009707:Nucleosomes