Early Prediction of Hypoxic-Ischemic Brain Damage in Newbon Rats Using Proton Magnetic Resonance Spectroscopy and Neuroprotective Effect of EGb 761

ABSTRACT

PURPOSE: This study was designed to evaluated the relationship between the morphological changes of hypoxic-ischemic injured brain and the magnetic resonance spectroscopic (MRS) findings, and the efficacy of Egb 761, a free radical scavenger, as a neuroprotective agent for hypoxic-ischemic brain injury. METHODS: Seven-day old Sprague-Dawley rat pups were used. Right common carotid artery was ligated under halothene anesthesia. After a recovery period of 3 hours, they were divided into two groups : for group 1, EGb 761 100 mg/kg (treatment group) and for group 2, normal saline (control group) were given intraperitoneally. Both groups were exposed to 8% oxygen at 37degrees C for 90 minutes. Sixty-four rat pups (30 control, 34 treatment group) were examined with localized 1H MRS on days 1 and 7 after the hypoxic insult. One day 14, the degree of brain injury was scored by morphological changes. RESULTS: The 1H MRS obtained on day 1 after the hypoxic insult showed increased Lip/NAA and Lip/Cr ratios in the right cerebral hemisphere in comparison with those in the left hemisphere (P<0.01). The degree of morphological changes of the brain injury on day 14 correlated with both Lip/NAA and Lip/Cr ratios obtained on days! and 7 after the hypoxic insult [r=0.410, 0.457 on day 1, and r=0.749, 0.720 on day 7, respectively (P< 0.01)]. The therapeutic potential of EGb 761 for the hypoxic-ischemic brain seemed insignificant, as was evident from no differences between the control group and the EGb 761 treatment group in the Lip/NAA and Lip/Cr ratios as well as in morphological changes. CONCLUSION: Early changes of Lip/NAA and Lip/Cr ratios in the 1H MRS seems to be related to the degree of morphological changes in the rat brain of hypoxic-ischemic injury. Therefore, the increased lipid content of brain observed by 1H MRS can be used as a marker to predict the degree of the hypoxic-ischemic injury. The neuroprotectiveeffect of EGb 761 in hypoxic-ischemic brain injury is insignificant.