Oxygen resuscitation does not ameliorate neonatal hypoxia/ischemia-induced cerebral edema.
Neonatal hypoxia/ischemia (HI) is a common cause of cognitive and behavioral deficits in children with hyperoxia treatment (HHI) being the current therapy for newborn resuscitation. HI induces cerebral edema that is associated with poor neurological outcomes. Our objective was to characterize cerebral edema after HI and determine the consequences of HHI (40% or 100% O(2)). Dry weight analyses showed cerebral edema 1 to 21 days after HI in the ipsilateral cortex; and 3 to 21 days after HI in the contralateral cortex. Furthermore, HI increased blood-brain barrier (BBB) permeability 1 to 7 days after HI, leading to bilateral cortical vasogenic edema. HHI failed to prevent HI-induced increase in BBB permeability and edema development. At the molecular level, HI increased ipsilateral, but not contralateral, AQP4 cortical levels at 3 and up to 21 days after HI. HHI treatment did not further affect HI-induced changes in AQP4. In addition, we observed developmental increases of AQP4 accompanied by significant reduction in water content and increase permeability of the BBB. Our results suggest that the ipsilateral HI-induced increase in AQP4 may be beneficial and that its absence in the contralateral cortex may account for edema formation after HI. Finally, we showed that HI induced impaired motor coordination 21 days after the insult and HHI did not ameliorate this behavioral outcome. We conclude that HHI treatment is effective as a resuscitating therapy, but does not ameliorate HI-induced cerebral edema and impaired motor coordination.
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, TX 77555-1072, USA.
Diana Carolina
DC
Ferrari
Olivera B
OB
Nesic
J Regino
JR
Perez-Polo
D000818:Animals; D000831:Animals, Newborn; D051401:Aquaporin 4 / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism; D001834:Body Water; D001921:Brain / Q000378:metabolism; D001929:Brain Edema / Q000209:etiology* / Q000378:metabolism / Q000628:therapy*; D002199:Capillary Permeability; D004195:Disease Models, Animal; D020820:Dyskinesias / Q000150:complications / Q000378:metabolism / Q000628:therapy; D007839:Functional Laterality; D020925:Hypoxia-Ischemia, Brain / Q000150:complications* / Q000378:metabolism / Q000628:therapy*; D010102:Oxygen Inhalation Therapy / Q000379:methods*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012151:Resuscitation / Q000379:methods*; D013997:Time Factors
C496032:Aqp4 protein, rat; D051401:Aquaporin 4