NEURONAL DAMAGE INDUCED BY PERINATAL ASPHYXIA IS ATTENUATED BY POSTINJURY GLUTAREDOXIN-2 ADMINISTRATION

ROMERO, JUAN IGNACIO; HOLUBIEC, MARIANA INÉS; TORNATORE, TAMARA LOGICA; RIVIÈRE, STÉPHANIE; HANSCHMANN, EVA-MARIA; KÖLLIKER-FRERS, RODOLFO ALBERTO; TAU, JULIA; BLANCO, EDUARDO; GALEANO, PABLO; RODRÍGUEZ DE FONSECA, FERNANDO; LILLIG, CHRISTOPHER HORST; CAPANI, FRANCISCO

OXIDATIVE MEDICINE AND CELLULAR LONGEVITY

LANDES BIOSCIENCE

Lugar: Austin, Texas; Año: 2017 vol. 2017 p. 1 - 14

1942-0900

The general disruption of redox signalingfollowing an ischemia-reperfusion episode has been proposed as a crucialcomponent in neuronal death and consequently brain damage. Thioredoxin (Trx)family proteins control redox reactions and ensure protein regulation viaspecific, oxidative posttranslational modifications as part of cellularsignaling processes. Trx proteins function in the manifestation, progression,and recovery following hypoxic/ischemic damage. Here, we analyzed theneuroprotective effects of postinjury, exogenous administration of Grx2 andTrx1 in a neonatal hypoxia/ischemia model. P7 Sprague-Dawley rats weresubjected to right common carotid ligation or sham surgery, followed by anexposure to nitrogen. 1 h later, animals were injected i.p. with salinesolution, 10 mg/kg recombinant Grx2 or Trx1, and euthanized 72 h postinjury.Results showed that Grx2 administration, and to some extent Trx1, attenuatedpart of the neuronal damage associated with a perinatal hypoxic/ischemicdamage, such as glutamate excitotoxicity, axonal integrity, and astrogliosis.Moreover, these treatments also prevented some of the consequences of theinduced neural injury, such as the delay of neurobehavioral development. To ourknowledge, this is the first study demonstrating neuroprotective effects ofrecombinant Trx proteins on the outcome of neonatal hypoxia/ischemia, implyingclinical potential as neuroprotective agents that might counteract neonatalhypoxia/ischemia injury.