Basic fibroblast growth factor reduces lactic acid-induced neuronal injuryin rat hippocampal neurons

Objective: To evaluate the long-term effects of lactic acidosis and to exam ine a potential neuroprotective role of basic fibroblast growth factor (bFG F) on hippocampal neurons. Design: Long-term observation in a cell-culture study. Setting: University research laboratory. Subjects: Adult, differentiated, primary rat hippocampal neurons. Interventions: Neurons were exposed to medium acidified with 20 mM lactic a cid, pH 6.2, for a 10-min period, and maintained untreated or in the presen ce of bFGF (500 pg/mL, 1 ng/mL, 10 ng/mL, 20 ng/mL) applied after exposure. Measurements and Main Results: Viability was analyzed by a dye inclusion/en zyme activity test and morphology by phase contrast and immunofluorescence microscopy. [H-3]Arachidonic acid (AA) release was measured by liquid scint illation spectrometry. All cultures appeared to be unchanged during the fir st days after exposure to lactic acidosis. Neurodegeneration became apparen t within 3 days. Seven days after exposure, cell survival decreased to 60% in lactic acidosis-injured, untreated cultures. Morphologic damage appeared as a 50% reduction in axonal and 25% reduction in dendritic arborizations. AA release increased to four-fold enhanced levels relative to control valu es, bFGF (1, 20, and 10 ngl mt) enhanced neuronal viability (p < .05), and 10 ng/mL bFGF induced a maximal increase in live cells to 80% of controls. Axonal arborizations increased to 50% and dendritic arborizations to 75% of controls after 10 ng/mL bFGF (p < .05). bFGF in a dose of 20 ngl mt enhanc ed axonal branching to 40% and dendrites in number and branching to 50% of controls (p < .05). bFGF (500 pg/mL, and 1 and 10 ng/mL) decreased enhanced AA (p < .05), and 10 ng/mL bFGF maximally reduced increased AA to two fold enhanced values relative to controls. Conclusions: In vulnerable neurons, exposure to moderate lactic acidosis in duces a process of cell injury with long latency. bFGF applied postinjury r educes the delayed neurodegeneration and may have neuroprotective efficacy in new therapeutic strategies to ischemia-induced cerebral injury.