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

被引：9

作者：

Lee, Choong-Hyun ^{[1
]}

Ahn, Ji Hyeon ^{[2
,3
]}

Lee, Tae-Kyeong ^{[4
]}

Sim, Hyejin ^{[3
]}

Lee, Jae-Chul ^{[3
]}

Park, Joon Ha ^{[5
]}

Shin, Myoung Cheol ^{[6
]}

Cho, Jun Hwi ^{[6
]}

Kim, Dae Won ^{[7
,8
]}

Won, Moo-Ho ^{[3
]}

Choi, Soo Young ^{[4
]}

机构：

[1] Dankook Univ, Coll Pharm, Dept Pharm, Cheonan 31116, Chungnam, South Korea

[2] Youngsan Univ, Coll Hlth Sci, Dept Phys Therapy, Yangsan 50510, Gyeongnam, South Korea

[3] Kangwon Natl Univ, Sch Med, Dept Neurobiol, Chunchon 24341, Gangwon, South Korea

[4] Hallym Univ, Dept Biomed Sci, Res Inst Biosci & Biotechnol, Chunchon 24252, Gangwon, South Korea

[5] Dongguk Univ, Coll Korean Med, Dept Anat, Gyeongju 38066, Gyeongbuk, South Korea

[6] Kangwon Natl Univ, Kangwon Natl Univ Hosp, Sch Med, Dept Emergency Med, Chunchon 24289, Gangwon, South Korea

[7] Gangnung Wonju Natl Univ, Coll Dent, Dept Biochem & Mol Biol, Kangnung 25457, Gangwon, South Korea

[8] Gangnung Wonju Natl Univ, Coll Dent, Res Inst Oral Sci, Kangnung 25457, Gangwon, South Korea

来源：

NEUROCHEMICAL RESEARCH | 2021年 / 46卷 / 11期

基金：

新加坡国家研究基金会;

关键词：

BBB disruption and leakage; Neuronal death; Ischemic duration; Ischemia-reperfusion injury; Microglia; Neuroinflammation; FLUORO-JADE B; CEREBRAL-ISCHEMIA; DAMAGE; DURATIONS; GLIOSIS; VULNERABILITY; MICROGLIA; STROKE; HISTOFLUORESCENCE; NEUROGENESIS;

D O I：

10.1007/s11064-021-03362-6

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-alpha) and interleukin 1 beta (IL-1 beta)] 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.

引用

页码：2852 / 2866

页数：15

共 59 条

[1] Early IV-injected human dermis-derived mesenchymal stem cells after transient global cerebral ischemia do not pass through damaged blood-brain barrier [J].