Comparison of Neuronal Death, Blood–Brain Barrier Leakage and Inflammatory Cytokine Expression in the Hippocampal CA1 Region Following Mild and Severe Transient Forebrain Ischemia in Gerbils

• Published in: Neurochemical research Vol. 46; no. 11; pp. 2852 - 2866
• Main Authors: Lee, Choong-Hyun, Ahn, Ji Hyeon, Lee, Tae-Kyeong, Sim, Hyejin, Lee, Jae-Chul, Park, Joon Ha, Shin, Myoung Cheol, Cho, Jun Hwi, Kim, Dae Won, Won, Moo-Ho, Choi, Soo Young
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.11.2021; Springer Nature B.V
• Subjects: Albumin; Albumins; Animals; Arteries; Biochemistry; Biomedical and Life Sciences; Biomedicine; Blood-brain barrier; Blood-Brain Barrier - metabolism; Blood-Brain Barrier - pathology; CA1 Region, Hippocampal - metabolism; CA1 Region, Hippocampal - pathology; Carotid arteries; Carotid artery; Cell Biology; Cell Death - physiology; Cerebral blood flow; Cytokines; Cytokines - biosynthesis; Cytokines - genetics; Damage; Death; Forebrain; Gene Expression; Gerbillinae; Hippocampus; IL-1β; Immunoglobulin G; Immunoreactivity; Inflammation; Inflammation Mediators - metabolism; Interleukin 1; Interleukin 13; Interleukin 4; Ischemia; Ischemic Attack, Transient - genetics; Ischemic Attack, Transient - metabolism; Ischemic Attack, Transient - pathology; Leakage; Male; Microglia; Mortality; Neurochemistry; Neurology; Neurons - metabolism; Neurons - pathology; Neurosciences; Occlusion; Original Paper; Plasma proteins; Severity of Illness Index; Tumor necrosis factor-TNF; Tumor necrosis factor-α; BBB disruption and leakage; Neuronal death; Neuroinflammation; Ischemia-reperfusion injury; Ischemic duration; Microglia
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-021-03362-6

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.