Activation of ERK1/2 after neonatal rat cerebral hypoxia-ischaemia

Abstract

Activation of extracellular signal-related kinases (ERK1/2), also known as p42/44 mitogen-activated protein kinase (MAPK), is considered important for neuronal survival, cell proliferation and apoptosis. In the present study, activation (phosphorylation) of ERK1/2 (P-ERK) was investigated in brains of 7-day-old rats after hypoxia-ischaemia (HI). In damaged areas, P-ERK-positive neurons appeared immediately after HI and the staining remained for at least 8 h. At later time points, 24 and 72 h post-HI, P-ERK-positive neurons were found in the core of the infarct and in the border zone to undamaged tissue. These cells also showed signs of DNA damage and calpain-induced fodrin breakdown, indicative of injury. At 72 h post-HI, P-ERK was also observed in microglia in the border zone to the damaged area and in astrocytes and oligodendrocytes in white matter of both hemispheres. P-ERK was strongly expressed in the subventricular zone in both hemispheres after HI at most time points, although the staining in the ipsilateral (damaged hemisphere) was stronger than in the contralateral (non-damaged hemisphere). In summary, ERK1/2 activation occurred early in neurons after HI in the neonatal brain, and mainly in cells displaying signs of damage.