ELEVATED BASIC FIBROBLAST GROWTH-FACTOR LEVELS IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

Basic fibroblast growth factor is a bioiogically active polypeptide wi th mitogenic, angiogenic and neurotrophic properties. In the present s tudy, the temporal and spatial expressions of basic fibroblast growth factor in stroke-prone spontaneously hypertensive rats were compared t o two related strains of rat: spontaneously hypertensive rats and norm otensive Wistar Kyoto rats. Higher levels of total RNA concentration w ere Found in cerebral cortex of four-week-old stroke-prone rats compar ed to spontaneously hypertensive rats and Wistar Kyoto rats. Northern blot analysis showed no changes in levels of basic fibroblast growth f actor messenger RNA with increasing age in cerebral cortex of Wistar K yoto and spontaneously hypertensive rats. However, significant increas es were found in 26- and 38-week-old stroke-prone rats compared to fou r-week-old stroke-prone rats. Although messenger RNA increases were al so found in subcortical and cerebellar regions, a significant differen ce in levels of basic fibroblast growth factor messenger RNA was obser ved only in cerebral cortices among these three strains. This age-rela ted increase in basic fibroblast growth factor messenger RNA correlate d with the increase incidence of stroke in stroke-prone rats. Immunohi stochemical study further revealed a dramatic increase in levels of ba sic fibroblast growth factor immunoreactivity in cerebral cortex of 30 -week-old stroke-prone rats as compared to young stroke-prone rats, as well as age-matched Wistar Kyoto and spontaneously hypertensive rats. This increase in basic fibroblast growth factor immunoreactivity ther efore appears very specific to aged stroke-prone rats. However, immuno reactivity decreased once severe tissue damages were observed in the c erebral cortex. Basic fibroblast growth factor-positive cells were dif fusely expressed in cerebral cortex double staining with glial fibrill ary acidic protein showed the majority of these basic fibroblast growt h factor-positive cells to be astrocytes. In summary, although young s troke-prone spontaneously hypertensive rats showed significantly highe r RNA concentration, significant increases in levels of basic fibrobla st growth Factor, including both messenger RNA and protein expression, were observed in aged stroke-prone rats with a high incidence of stro ke. These findings suggest the possibility that basic fibroblast growt h factor may play a role in the developmental sequelae of cerebral les ions in stroke-prone spontaneously hypertensive rats. Copyright (C) 19 96 IBRO.