Oxygen resuscitation does not ameliorate neonatal hypoxia/ischemia-induced edema

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Title: Oxygen resuscitation does not ameliorate neonatal hypoxia/ischemia-induced edema
Author: Diana Carolina Ferrari
Abstract: Neonatal hypoxia /ischemia (HI ) is the most common cause of developmental neurological , cognitive and behavioral deficits in children . Although cerebral edema is a common outcome after HI , the mechanisms leading to the excessive fluid accumulation are poorly understood . Hyperoxia treatment after HI (HHI ) is the recommended clinical therapy for newborn resuscitation . Our objective was to evaluate edema development after HI and whether HHI treatment affected HI -induced edema . We induced HI by a permanent ligation of the left carotid artery followed by a systemic exposure to hypoxia (8 % O2 ) in P7 rats ; a cohort of these animals was immediately treated with hyperoxia (40 % or 100 % O2 ) . Dry weight analyses and T2 -MRI showed cerebral edema 1 , 3 , 7 and 21 days after HI in the ipsilateral cortex , and 3 , 7 and 21 days in the contralateral cortex . Using a blood -brain barrier (BBB ) assay we showed that HI induces BBB permeability 3 and 7 days after HI , leading to vasogenic edema in both cortices . HHI treatment failed to prevent BBB permeability and edema development . At the molecular level , we investigated the effect of HI on AQP4 , the main water channel in the brain , which has been implicated in edema development after different neuropathological conditions . Our results showed that HI significantly increased AQP4 levels 3 , 7 and 21 days after HI in the ipsilateral cortex , with no effect in the contralateral cortex . Furthermore , HHI treatment did not affect HI -induced changes in AQP4 , consistent with the lack of effect of HHI on edema development . Given that developmental increases of AQP4 in the brain are accompanied by significant reduction in water content , we believe that HI -induced increase in AQP4 in the ipsilateral cortex is aimed at protecting the brain , and that the lack of increase in AQP4 levels in the contralateral cortex leads to the development of edema . In agreement with our hypothesis , 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 .
URI: http : / /hdl .handle .net /2152 .3 /138
Date: 2009-03-20

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Oxygen resuscitation does not ameliorate neonatal hypoxia/ischemia-induced edema. Doctoral dissertation, The University of Texas Medical Branch. Available electronically from http : / /hdl .handle .net /2152 .3 /138 .

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