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Vogel, P; Putten, H; Popp, E; Krumnikl, JJ; Teschendorf, P; Galmbacher, R; Kisielow, M; Wiessner, C; Schmitz, A; Tomaselli, KJ; Schmitz, B; Martin, E; Böttiger, BW.
Improved resuscitation after cardiac arrest in rats expressing the baculovirus caspase inhibitor protein p35 in central neurons.
Anesthesiology. 2003; 99(1): 112-121. Doi: 10.1097/00000542-200307000-00020 [OPEN ACCESS]
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Krumnikl Jakub
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Abstract:
BACKGROUND: Global cerebral ischemia is associated with delayed neuronal death. Given the role of caspases in apoptosis, caspase inhibitors may provide neuronal protection after cardiac arrest. To this end, the authors generated a transgenic rat line expressing baculovirus p35, a broad-spectrum caspase inhibitor, in central neurons. Its effects were evaluated on neuronal cell death and outcome after global cerebral ischemia. METHODS: Global cerebral ischemia was induced by cardiocirculatory arrest. After 6 min, animals were resuscitated by controlled ventilation, extrathoracic cardiac massage, epinephrine, and electrical countershocks. Neuronal death was assessed after 7 days by histologic evaluation of the hippocampal cornu ammonis 1 sector. Postischemic outcome was assessed by determination of overall survival and according to neurologic deficit scores 24 h, 3 days, and 7 days after resuscitation. RESULTS: The rate of 7-day survival after cardiac arrest for the transgenic rats (85%) was significantly higher than that for the nontransgenic controls (52%; P < 0.05). However, no differences were observed either in the number of terminal deoxynucleotidyltransferase-mediated d-uracil triphosphate-biotin nick end-labeling-positive cells or viable neurons in the cornu ammonis 1 sector or in the neurologic deficit score when comparing surviving transgenic and nontransgenic rats. These findings suggest that neuronal apoptosis after cardiac arrest is not primarily initiated by activation of caspases. CONCLUSION: Expression of baculovirus p35 can improve survival after cardiac arrest in rats, but the mode and site of action remain to be elucidated.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Animals, Genetically Modified -
Baculoviridae - metabolism
Blotting, Northern - metabolism
Blotting, Southern - metabolism
Blotting, Western - metabolism
Brain Chemistry - genetics
Brain Ischemia - pathology
Cardiopulmonary Resuscitation - pathology
Caspases - antagonists and inhibitors
Cell Death - physiology
Electroshock - physiology
Enzyme Inhibitors - metabolism
Heart Arrest - physiopathology
Hippocampus - pathology
In Situ Hybridization - pathology
In Situ Nick-End Labeling - pathology
Inhibitor of Apoptosis Proteins - pathology
Microinjections - pathology
Nervous System Diseases - etiology
Neurons - pathology
Rats - pathology
Rats, Wistar - pathology
Survival - pathology
Viral Proteins - biosynthesis

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