Establishment of a Neonatal Rat Model of Hypoxic-Ischemic Brain Damage

Objective To establish an animal model mimicking neurobehavioral characteristics and pathological changes in term human neonates with hypoxic-ischemic brain damage(HIBD),and thus to study the pathophysiological mechanisms and therapies in term neonates with HIBD.Methods Postnatal day 10 SD rats underwent hypoxic-ischemic(experimental group) or sham(control) treatment.For both groups,each rat was anesthetized with ethylether.In the experimental group,the right common carotid artery of rats was ligated and exposed to hypoxia in a chamber filling with 8% oxygen(balanced with nitrogen) for 2.5 h.For the sham control,the right common carotid artery was surgically exposed,but not ligated or exposed to hypoxia.Longa score was used to assess the neuropathology.Rat brains were collected at 4 h,8 h and 24 h after treatment.HE staining was used to detect neuronal pathological changes.The apoptotic marker,cleaved caspase-3(CC3) protein,was detected with immunohistochemistry.TUNEL method was used to detect apoptosis.Results Cell swelling,necrosis,and rarefaction were observed in the experimental group but not in the sham control group by HE staining.The expression of CC3 protein as well as the TUNEL positive cells were expressed at 4 h and peaked at 24 h after hypoxia-ischemia in the experimental rats,which was significantly higher compared to that in the sham control group(P0.01).There were different degrees of neurological impairment in the experimental group.The Longa Score was significantly higher compared to that in the sham control group(P0.01).Conclusion The neurobehavioral characteristics and pathological changes in this rat model are consistent with the changes in term human neonatal HIBD.Therefore,this model can be used to study pathophysiological mechanisms and therapies for term human neonatal HIBD.