Abstract
Current study explores the feasibility of using a non-surgical method of oxygen deprivation to create Hypoxic brain damage in neonatal rats for medical studies. 7-day-old Sprague Dowley (SD) rats were kept in a container with low oxygen level (8%) for 1.5h. A second group had bilateral cephalic artery ligation before the 1.5h-low oxygen treatment, a method similar to the popular Rice method, to expose the brain to both hypoxic and ischemic situations. Short term neural functions and brain water weights were evaluated 1 day after the hypoxic treatment. Brain pathology and histology were also examined at 1 day and 3 days after the hypoxic treatment. Both groups showed impaired neural functions and increased brain water weight compared to the controls. Histology studies also revealed injuries in the subcortex, hippocampus and lateral ventricle in the brains from both groups. There is no significant difference in the degree of brain damages observed in the two groups. Our work demonstrated that oxygen deprivation alone is sufficient to cause brain damages similar to those seen in Hypoxic-ischemic brain disease (HIBD). Because this method avoids the invasive surgical procedure and therefore reduces the stress and mortality of laboratory animals during the experiment, we recommend it to be the favorable method for creating rat models for HIBD studies.
Highlights
Hypoxic-ischemic brain disease (HIBD) is the brain damage in newborn infants caused by partial or total hypoxia and decreased cerebral blood supply due to perinatal asphyxia [1]
1d after the surgery and low oxygen treatment, both the hypoxic group and the hypoxic+ischemic group recorded significantly longer reflex time for the righting reflex test and the geotactic reflex test compared to the controls while there is no significant difference between the two groups in either of the tests (Table 1)
There is no significant difference in the brain water content between the hypoxic group and the ischemic+hypoxic group but both were significantly higher than the controls (Table 3)
Summary
Hypoxic-ischemic brain disease (HIBD) is the brain damage in newborn infants caused by partial or total hypoxia and decreased cerebral blood supply due to perinatal asphyxia [1]. The procedure requires unilateral ligation of carotid artery in a 7d old rat followed by 2.5 to 3h of low oxygen concentration (8%) treatment This method does simulate the newborn HIBD. The unilateral ligation surgery is invasive and may cause partial ischemic injury in the brain during the operation It is a difficult procedure and trauma caused by the surgery and the anesthesia procedure is tremendous for neonatal rats. Congle Zhou [9] et al have successfully created porcine models for brain anoxia by oxygen deprivation alone as well as by combining bilateral carotid artery ligation and oxygen deprivation They have demonstrated that various degrees of cerebral injury can be observed 72h after anoxia and there was no significant difference in the physiological parameters, cerebral blood flow and cerebral perfusion in newborn pigs after the two procedures. This shows that oxygen deprivation alone is sufficient to simulate HIBD conditions in newborn pigs and surgical ligation of carotid arteries may not be necessary
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