A persistent change in subcellular distribution of calcineurin following fluid percussion injury in the rat

Abstract

Calcineurin, a neuronally enriched, calcium-stimulated phosphatase, is an important modulator of many neuronal processes, including several that are physiologically related to the pathology of traumatic brain injury. The effect of moderate, central fluid percussion injury on the subcellular distribution of this important neuronal enzyme was examined. Animals were sacrificed at several time points post-injury and calcineurin distribution in subcellular fractions was assayed by Western blot analysis and immunohistochemistry. A persistent increase in calcineurin concentration was observed in crude synaptoplasmic membrane-containing fractions. In cortical fractions, calcineurin immunoreactivity remained persistently increased for 2 weeks post-injury. In hippocampal homogenates, calcineurin immunoreactivity remained increased for up to 4 weeks. Finally, immunohistochemical analysis of hippocampal slices revealed increased staining in the apical dendrites of CA1 neurons. The increased staining was greatest in magnitude 24 h post-injury; however, staining was still more intense than control 4 weeks post-injury. The data support the conclusion that fluid percussion injury results in redistribution of the enzyme in the rat forebrain. These changes have broad physiological implications, possibly resulting in altered cellular excitability or a greater likelihood of neuronal cell death.