Perinatal hypoxic鈥搃schemic
brain injury is an important cause of neurological deficits still causing mortality and morbidity in the
early period of life. As efficient clinical or pharmaceutical strategies to prevent or reduce the outcome of perinatal hypoxic鈥搃schemic
brain damage are limited, the development of new therapies is of utmost importance. To evolve innovative therapeutic concepts, elucidation of the mechanisms contributing to the neurological impairments upon hypoxic鈥搃schemic
brain injury is necessary. Therefore, we aimed for the identification of proteins that are affected by hypoxic鈥搃schemic
brain injury in neonatal rats. To assess changes in protein expression two days after induction of
brain damage, a 2D-DIGE based proteome analysis was performed. Among the proteins altered after hypoxic鈥搃schemic
brain injury, Calcineurin A, Coronin-1A, as well as GFAP were identified, showing higher expression in lesioned hemispheres. Validation of the changes in Calcineurin A expression by Western Blot analysis demonstrated several truncated forms of this protein generated by limited proteolysis after hypoxia鈥搃schemia. Further analysis revealed activation of calpain, which is involved in the limited proteolysis of Calcineurin. Active forms of Calcineurin are associated with the dephosphorylation of Darpp-32, an effect that was also demonstrated in lesioned hemispheres after perinatal
brain injury.
Keywords:
hypoxia-ischemia; brain+injury&qsSearchArea=searchText">brain injury; 2D-DIGE; proteomics; mass spectrometry