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Proteomic Analysis of Alterations Induced by Perinatal Hypoxic–Ischemic Brain Injury
journal contribution
posted on 2012-12-07, 00:00 authored by Katja Rosenkranz, Caroline May, Carola Meier, Katrin MarcusPerinatal hypoxic–ischemic 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–ischemic
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–ischemic brain injury is necessary. Therefore, we aimed
for the identification of proteins that are affected by hypoxic–ischemic
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–ischemic
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–ischemia. 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.