Inflammation contributes to the evolution of hypoxic-ischemic (HI)
brain injury. High-mobility group box-1 (
HMGB1) is a
nuclear protein that is translocated from the nucleus and released after
ischemia in adult rodents and thereby initiates inflammatory responses. However, there is very little information regarding the effects of HI on
HMGB1 in immature brains. To investigate the effects of HI on
HMGB1 in the term-equivalent fetal brain, ovine fetuses at 127 days gestation were studied after 30 minutes of carotid occlusion. Groups were
sham-control and
ischemia with 48 hours and
ischemia with 72 hours of reperfusion. By immunohistochemistry,
HMGB1 was found to be localized primarily in cell nuclei and partially in cytoplasmic compartments in the cerebral cortex of controls.
Ischemia increased the area fraction of neuronal cells with cytoplasmic
HMGB1 staining, and Western immunoblot revealed that cytosolic
HMGB1 expression increased after
ischemia (p < 0.05) and decreased in nuclei in ischemic versus the
sham-control brains (p < 0.05). These data indicate that
HMGB1 translocates from the nuclear to cytosolic compartments after ischemic
brain injury in fetal sheep. This translocation may enable the action of
HMGB1 as a proinflammatory
cytokine that contributes to HI injury in the developing brain.