Transient
ischemia in the brain causes blood-brain barrier (BBB) breakdown and dysfunction, which is related to
ischemia-induced neuronal damage. Leakage of
plasma proteins following transient
ischemia is one of the indicators that is used to determine the extent of BBB dysfunction. In this study, neuronal damage/death, leakage of
albumin and
IgG, microgliosis, and inflammatory
cytokine expression were examined in the hippocampal CA1 region, which is vulnerable to transient
ischemia, following 5-min (mild) and 15-min (severe)
ischemia in gerbils induced by transient common carotid arteries occlusion (tCCAo). tCCAo-induced neuronal damage/death occurred earlier and was more severe after 15-min tCCAo vs. after 5-min tCCAo. Significant
albumin and
IgG leakage (
albumin and
IgG immunoreactivity) took 1 or 2 days to begin, and immunoreactivity was markedly increased 5 days after 5-min tCCAo. While,
albumin and
IgG leakage began to increase 6 h after 15-min tCCAo and remained significantly higher over time than that seen in 5-min tCCAo.
IgG immunoreactivity was observed in degenerating neurons and activated microglia after tCCAo, and microglia were activated to a greater extent after 15-min tCCAo than 5-min tCCAo. In addition, following 15-min tCCAo, pro-inflammatory
cytokines [
tumor necrosis factor alpha (TNF-α) and
interleukin 1 beta (IL-1β)] immunoreactivity was significantly higher than that seen following 5-min tCCAo, whereas immunoreactivity of anti-inflammatory
cytokines (IL-4 and IL-13) was lower in 15-min than 5-min tCCAo. These results indicate that duration of tCCAo differentially affects the timing and degree of neuronal damage or loss,
albumin and
IgG leakage and inflammatory
cytokine expression in brain tissue. In addition, more severe BBB leakage is closely related to acceleration of neuronal damage through increased microglial activation and pro-inflammatory
cytokine expression in the ischemic hippocampal CA1 region.