It has been suggested that propofol has the protective effect on cerebral ischemia-reperfusion injury. The aim of this study is to evaluate the effect of propofol pretreatment on incomplete forebrain ischemia-reperfusion injury in rats. Thirty Sprague-Dawley rats were anesthetized with isoflurane in oxygen and randomly allocated into propofol group (n=13) and saline group (n=17). In propofol group, propofol was pretreated in a step-down scheme before inducing forebrain ischemia by occlusion of both common carotid arteries and arterial hypotension. After ischemia (20 min) and reperfusion (30 min), rats were decapitated. Brain was sliced to obtain coronal slices of 4-12 mm from frontal pole, which were reacted with 2% 2,3,5-triphenyl-2H-tetrazolium chloride (TTC) for 10 min to differentiate the damaged tissues from normal tissues. Median (interquartile range) values of the average percent infarct area were 0.0 (8.6)% and 20.1 (41.2)% in propofol and saline groups, respectively. There was significant difference between the groups. In conclusion, propofol may have a protective effect on incomplete forebrain ischemia-reperfusion injury.
Animal ; Brain Ischemia/prevention & control* ; Brain Ischemia/pathology ; Cerebral Infarction/prevention & control ; Cerebral Infarction/pathology ; Disease Models, Animal ; Free Radical Scavengers/pharmacology* ; Mitochondria/enzymology* ; Neuroprotective Agents/pharmacology* ; Oxidative Phosphorylation ; Propofol/pharmacology* ; Prosencephalon/metabolism ; Prosencephalon/injuries ; Prosencephalon/drug effects* ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury/prevention & control* ; Reperfusion Injury/pathology ; Tetrazolium Salts

Reactive oxygen species (ROS) contribute to the development of a number of neuronal diseases including ischemia. DJ-1, also known to PARK7, plays an important role in transcriptional regulation, acting as molecular chaperone and antioxidant. In the present study, we investigated whether DJ-1 protein shows a protective effect against oxidative stress-induced neuronal cell death in vitro and in ischemic animal models in vivo. To explore DJ-1 protein's potential role in protecting against ischemic cell death, we constructed cell permeable Tat-DJ-1 fusion proteins. Tat-DJ-1 protein efficiently transduced into neuronal cells in a dose- and time-dependent manner. Transduced Tat-DJ-1 protein increased cell survival against hydrogen peroxide (H2O2) toxicity and also reduced intracellular ROS. In addition, Tat-DJ-1 protein inhibited DNA fragmentation induced by H2O2. Furthermore, in animal models, immunohistochemical analysis revealed that Tat-DJ-1 protein prevented neuronal cell death induced by transient forebrain ischemia in the CA1 region of the hippocampus. These results demonstrate that transduced Tat-DJ-1 protein protects against cell death in vitro and in vivo, suggesting that the transduction of Tat-DJ-1 may be useful as a therapeutic agent for ischemic injuries related to oxidative stress.
Animals ; Blood-Brain Barrier/metabolism ; Brain Ischemia/*metabolism/pathology/prevention & control ; CA1 Region, Hippocampal/drug effects/metabolism/pathology ; Cell Line, Tumor ; Cell Survival/drug effects ; Gerbillinae ; Intracellular Signaling Peptides and Proteins/*administration & dosage/biosynthesis/pharmacokinetics ; Lipid Peroxidation ; Malondialdehyde/metabolism ; Mice ; Neuroprotective Agents/*administration & dosage/pharmacokinetics ; Oncogene Proteins/*administration & dosage/biosynthesis/pharmacokinetics ; *Oxidative Stress ; Prosencephalon/drug effects/metabolism/pathology ; Rats ; Recombinant Fusion Proteins/*administration & dosage/biosynthesis/pharmacokinetics ; tat Gene Products, Human Immunodeficiency Virus/*administration & dosage/biosynthesis/pharmacokinetics