Abstract 2040 Neurology Platform, Sunday, 5/2

Perinatal insults such as iron deficiency (ID) and hypoxia-ischemia (HI) are common in infants of diabetic mothers and intrauterine growth retarded infants. These may affect the long-term, hippocampus based, cognitive impairments described in these infants. We have demonstrated loss of hippocampal cytochrome oxidase (CytOx) activity in vitro, with or without a superimposed HI insult, in ID 7d rats. The aim of the study was to evaluate the feasibility of 1H MRS with a 9.4 T magnet in assessing hippocampal metabolism in vivo following perinatal insults. After anatomic localization, 1H MRS was obtained from a volume of 3×2×4 voxels within the hippocampus (32 scans/animal) in 3 experimental conditions: 1) two ID (mean brain iron concentration: 55% of normal) and 1 iron sufficient (IS) rats were studied on d7. MRS was obtained 1h after unilateral HI injury (immature Levine model) in the IS rat and in 1 ID rat (ID+HI). The other ID rat was not subjected to HI injury (ID w/o HI). The MRS of the ID w/o HI rat and the IS rat were similar. The MRS from the ID+HI rat demonstrated elevated lactate (peak at 1.33ppm) ipsilaterally. Thus, only combined perinatal brain ID and HI injury appears to result in immediate hippocampal metabolic alterations. 2) In an 18d IS rat, MRS obtained 2h post HI injury did not demonstrate any metabolic change on the ligated side. However on d28, stroke lesions were present in the MR image and the MRS demonstrated abnormal peaks at ppm 0.87 and 1.272 (frequencies correspond to free fatty acids and lipids) ipsilaterally. Subsequent histochemistry confirmed cortical necrosis, ipsilateral hippocampal CytOx activity loss and Nissl loss. 3) Comparison of MRS in rats of different ages demonstrated increasing N-acetyl-L-aspartate (NAA) peak with advancing age in developing rats (28d>10d>7d). Since NAA is specific to neurons and is probably involved in myelination and neurotransmission, the adverse effect of perinatal ID on these aspects of neurodevelopment could thus be assessed by MRS. Hence 1H MRS with a 9.4 T magnet appears to be a sensitive in vivo method for evaluating brain metabolism in developing rats over time. Because of its high resolution power, minute metabolic changes in very small volumes of interest, such as within the hippocampus, which is preferentially vulnerable to common perinatal insults, could be evaluated. Sequential MRS could be used to obtain longitudinal developmental data in the same animal.

(Supported by NICHD)