INTRODUCTION: [corrected] Hypoxia-ischemia (HI) injury in term infants develops with a delay during the recovery phase, opening up a therapeutic window after the insult. Hypothermia is currently an established neuroprotective treatment in newborns with neonatal encephalopathy (NE), saving one in nine infants from developing neurological deficits. Caspase-2 is an initiator caspase, a key enzyme in the route to destruction and, therefore, theoretically a potential target for a pharmaceutical strategy to prevent HI brain damage. METHODS: The aim of this study was to explore the neuroprotective efficacy of hypothermia in combination with caspase-2 gene deficiency using the neonatal Rice-Vannucci model of HI injury in mice. RESULTS: HI brain injury was moderately reduced in caspase-2(-/-) mice as compared with wild-type (WT) mice. Five hours of hypothermia (33 °C ) vs. normothermia (36 °C) directly after HI provided additive protection overall (temperature P = 0.0004, caspase-2 genotype P = 0.0029), in the hippocampus and thalamus, but not in other gray matter regions or white matter. Delayed hypothermia initiated 2 h after HI in combination with caspase-2 gene deficiency reduced injury in the hippocampus, but not in other brain areas. DISCUSSION: In conclusion, caspase-2 gene deficiency combined with hypothermia provided enhanced neuroprotection as compared with hypothermia alone.
INTRODUCTION: [corrected] Hypoxia-ischemia (HI) injury in term infants develops with a delay during the recovery phase, opening up a therapeutic window after the insult. Hypothermia is currently an established neuroprotective treatment in newborns with neonatal encephalopathy (NE), saving one in nine infants from developing neurological deficits. Caspase-2 is an initiator caspase, a key enzyme in the route to destruction and, therefore, theoretically a potential target for a pharmaceutical strategy to prevent HI brain damage. METHODS: The aim of this study was to explore the neuroprotective efficacy of hypothermia in combination with caspase-2 gene deficiency using the neonatal Rice-Vannucci model of HI injury in mice. RESULTS:HI brain injury was moderately reduced in caspase-2(-/-) mice as compared with wild-type (WT) mice. Five hours of hypothermia (33 °C ) vs. normothermia (36 °C) directly after HI provided additive protection overall (temperature P = 0.0004, caspase-2 genotype P = 0.0029), in the hippocampus and thalamus, but not in other gray matter regions or white matter. Delayed hypothermia initiated 2 h after HI in combination with caspase-2gene deficiency reduced injury in the hippocampus, but not in other brain areas. DISCUSSION: In conclusion, caspase-2 gene deficiency combined with hypothermia provided enhanced neuroprotection as compared with hypothermia alone.
Authors: Burak Ozaydin; Ela Bicki; Onur E Taparli; Temour Z Sheikh; Danielle K Schmidt; Sefer Yapici; Margarett B Hackett; Nida Karahan-Keles; Jens C Eickhoff; Karson Corcoran; Claudia Lagoa-Miguel; Jose Guerrero Gonzalez; Douglas C Dean Iii; Andre M M Sousa; Peter A Ferrazzano; Jon E Levine; Pelin Cengiz Journal: Dev Neurosci Date: 2022-05-25 Impact factor: 3.421
Authors: Jia Liu; R Ann Sheldon; Mark R Segal; Mark J S Kelly; Jeffrey G Pelton; Donna M Ferriero; Thomas L James; Lawrence Litt Journal: Pediatr Res Date: 2013-05-24 Impact factor: 3.756