Dopamine treatment during acute hypoxia is neuroprotective in the developing sheep brain.
Dopamine is often used to treat hypotension in preterm infants; these infants are at risk of developing brain injury due to impaired autoregulation and cerebral hypoperfusion. However the effects of dopamine on the immature brain under conditions of cerebral hypoxia are not known. We hypothesized that pretreatment with dopamine would protect the immature brain from injury caused by cerebral hypoxia. Preterm fetal sheep were used to determine the effects of intravenous dopamine on hypoxia-induced brain injury. In 16 pregnant sheep at 90days of gestation (0.6 of term, term=147days) catheters were implanted aseptically into the fetal carotid artery and jugular vein; an inflatable occluder was placed loosely around the umbilical cord for later induction of fetal hypoxemia. At 5days after surgery, dopamine (10μg/kg/min, n=7 fetuses) or saline (n=9 fetuses) was infused for 74h. Two hours after commencing the dopamine/saline infusion, we induced umbilical cord occlusion (UCO) for up to 25min to produce fetal asphyxia. Fetuses were allowed to recover, and brains were collected 72h later for assessment of neuropathology. Un-operated twin fetuses were used as age-matched non-UCO controls (n=8). In UCO+saline fetuses, microglial and apoptotic cell density in the subcortical and periventricular white matter, caudate nucleus and hippocampus was greater than that in age-matched controls; oxidative stress was elevated in the subcortical and periventricular white matter and caudate nucleus compared to that in age-matched controls. In UCO+dopamine fetuses microglial density and oxidative stress in the cerebral white matter and caudate nucleus were not different to that of age-matched controls. Apoptotic cell death was decreased in the cerebral white matter of UCO+dopamine brains, relative to UCO+saline brains. We conclude that pretreatment with dopamine does not exacerbate hypoxia-induced injury in the immature brain and may be neuroprotective because it led to decreased apoptosis, oxidative stress and neuroinflammation in the cerebral white matter and decreased neuroinflammation in the caudate nucleus.
['Brew|N|N|', 'Azhan|A|A|', 'den Heijer|I|I|', 'Boomgardt|M|M|', 'Davies|G I|GI|', 'Nitsos|I|I|', 'Miller|S L|SL|', 'Walker|A M|AM|', 'Walker|D W|DW|', 'Wong|F Y|FY|']
D000367:Age Factors D000818:Animals D000831:Animals, Newborn D017209:Apoptosis D001835:Body Weight D001921:Brain D001930:Brain Injuries D002135:Calcium-Binding Proteins D004195:Disease Models, Animal D004298:Dopamine D004622:Embryo, Mammalian D005260:Female D005312:Fetal Blood D005311:Fetal Hypoxia D006339:Heart Rate D002534:Hypoxia, Brain D008840:Microfilament Proteins D009419:Nerve Tissue Proteins D018696:Neuroprotective Agents D018384:Oxidative Stress D011247:Pregnancy D012756:Sheep
dopamine hypotension white matter inotrope microglia preterm brain injury