We examined the effects of forebrain ischemia on white matter changes in ovine fetuses using the method of Williams et al. (Ped Res, 1990). 126 day gestation fetuses were exposed to 48 or 72 hrs of reperfusion (Rep) after a 30 min carotid occlusion or sham treatment. Groups (grps) were: sham (n=5), and 48 (n=7) or 72 (n=3) hrs of Rep. Whole brain coronal sections stained with Luxol fast blue-H&E were scored for white matter, hippocampal and cortical lesions. All areas received histologic scores 0-4 where 0=0%, 1=1-25%, 2=26-50%, 3=51-75% and 4= 75%- 100 of the area damaged. Dual label immunofluorescence using antibodies against glial fibrillary acidic protein(GFAP) and myelin basic protein (MBP) were used to characterize white matter lesions in 48 hr Rep (n=4) paired with similar neuroanatomic areas from sham brains (n=2). Computerized color analysis quantified% MBP and GFAP within lesions. Histologic scoring showed (median, range): White matter scores of 48 hr Rep (3, 1-4) and 72 hour Rep (4, 4) differed (p < 0.05) from the sham(0, 0-2) grp. White matter scores for 48 hr (3, 1-4) and 72 hr Rep (4, 4-4) were similar. Cortical scores in the 72 hour Rep grp (4, 3-4) differed from the sham (1, 0-2) grp. Other group differences were not seen in the cortex or hippocampus. White matter lesions were characterized by reactive astrocytes and a loss of oligodendroglial MBP. In ischemic lesions vs sham areas, MBP was 22±2 (M±SEM) vs 76-87% and GFAP was 10±2 vs 2.8-3.7%. We speculate that the observed injury may provide a basis for studies into the etiology of white mater damage in the ovine fetus. NIH HD/NS 34618-01
