Abstract
Remote ischemic perconditioning (PerC) has been proved to have neuroprotective effects on cerebral ischemia, however, the effect of PerC on the BBB disruption and underlying mechanisms remains largely unknown. To address these issues, total 90 adult male Sprague Dawley (SD) rats were used. The rats underwent 90-min middle cerebral artery occlusion (MCAO), and the limb remote ischemic PerC was immediately applied after the onset of MCAO. We found that limb remote PerC protected BBB breakdown and brain edema, in parallel with reduced infarct volume and improved neurological deficits, after MCAO. Immunofluorescence studies revealed that MCAO resulted in disrupted continuity of claudin-5 staining in the cerebral endothelial cells with significant gap formation, which was significantly improved after PerC. Western blot analysis demonstrated that expression of tight junction (TJ) protein occludin was significantly increased, but other elements of TJ proteins, claudin-5 and ZO-1, in the BBB endothelial cells were not altered at 48 h after PerC, compared to MCAO group. The expression of matrix metalloproteinase (MMP-9), which was involved in TJ protein degradation, was decreased after PerC. Interestingly, phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2), an upstream of MMP-9 signaling, was significantly reduced in the PerC group. Our data suggest that PerC inhibits MMP-9-mediated occludin degradation, which could lead to decreased BBB disruption and brain edema after ischemic stroke.
| Original language | English |
|---|---|
| Pages (from-to) | 406-417 |
| Number of pages | 12 |
| Journal | Aging and Disease |
| Volume | 6 |
| Issue number | 6 |
| DOIs | |
| State | Published - 1 Jan 2015 |
Fingerprint
Keywords
- Blood-brain barrier
- Ischemic stroke
- Matrix metalloproteinases
- Remote ischemic perconditioning
- Tight junction
Cite this
}
Limb ischemic perconditioning attenuates blood-brain barrier disruption by inhibiting activity of MMP-9 and occludin degradation after focal cerebral ischemia. / Ren, Changhong; Li, Ning; Wang, Brian; Yang, Yong; Gao, Jinhuan; Li, Sijie; Ding, Yuchuan; Jin, Kunlin; Ji, Xunming.
In: Aging and Disease, Vol. 6, No. 6, 01.01.2015, p. 406-417.Research output: Contribution to journal › Article
TY - JOUR
T1 - Limb ischemic perconditioning attenuates blood-brain barrier disruption by inhibiting activity of MMP-9 and occludin degradation after focal cerebral ischemia
AU - Ren, Changhong
AU - Li, Ning
AU - Wang, Brian
AU - Yang, Yong
AU - Gao, Jinhuan
AU - Li, Sijie
AU - Ding, Yuchuan
AU - Jin, Kunlin
AU - Ji, Xunming
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Remote ischemic perconditioning (PerC) has been proved to have neuroprotective effects on cerebral ischemia, however, the effect of PerC on the BBB disruption and underlying mechanisms remains largely unknown. To address these issues, total 90 adult male Sprague Dawley (SD) rats were used. The rats underwent 90-min middle cerebral artery occlusion (MCAO), and the limb remote ischemic PerC was immediately applied after the onset of MCAO. We found that limb remote PerC protected BBB breakdown and brain edema, in parallel with reduced infarct volume and improved neurological deficits, after MCAO. Immunofluorescence studies revealed that MCAO resulted in disrupted continuity of claudin-5 staining in the cerebral endothelial cells with significant gap formation, which was significantly improved after PerC. Western blot analysis demonstrated that expression of tight junction (TJ) protein occludin was significantly increased, but other elements of TJ proteins, claudin-5 and ZO-1, in the BBB endothelial cells were not altered at 48 h after PerC, compared to MCAO group. The expression of matrix metalloproteinase (MMP-9), which was involved in TJ protein degradation, was decreased after PerC. Interestingly, phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2), an upstream of MMP-9 signaling, was significantly reduced in the PerC group. Our data suggest that PerC inhibits MMP-9-mediated occludin degradation, which could lead to decreased BBB disruption and brain edema after ischemic stroke.
AB - Remote ischemic perconditioning (PerC) has been proved to have neuroprotective effects on cerebral ischemia, however, the effect of PerC on the BBB disruption and underlying mechanisms remains largely unknown. To address these issues, total 90 adult male Sprague Dawley (SD) rats were used. The rats underwent 90-min middle cerebral artery occlusion (MCAO), and the limb remote ischemic PerC was immediately applied after the onset of MCAO. We found that limb remote PerC protected BBB breakdown and brain edema, in parallel with reduced infarct volume and improved neurological deficits, after MCAO. Immunofluorescence studies revealed that MCAO resulted in disrupted continuity of claudin-5 staining in the cerebral endothelial cells with significant gap formation, which was significantly improved after PerC. Western blot analysis demonstrated that expression of tight junction (TJ) protein occludin was significantly increased, but other elements of TJ proteins, claudin-5 and ZO-1, in the BBB endothelial cells were not altered at 48 h after PerC, compared to MCAO group. The expression of matrix metalloproteinase (MMP-9), which was involved in TJ protein degradation, was decreased after PerC. Interestingly, phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2), an upstream of MMP-9 signaling, was significantly reduced in the PerC group. Our data suggest that PerC inhibits MMP-9-mediated occludin degradation, which could lead to decreased BBB disruption and brain edema after ischemic stroke.
KW - Blood-brain barrier
KW - Ischemic stroke
KW - Matrix metalloproteinases
KW - Remote ischemic perconditioning
KW - Tight junction
UR - http://www.scopus.com/inward/record.url?scp=84975780363&partnerID=8YFLogxK
U2 - 10.14336/AD.2015.0812
DO - 10.14336/AD.2015.0812
M3 - Article
AN - SCOPUS:84975780363
VL - 6
SP - 406
EP - 417
JO - Aging and Disease
JF - Aging and Disease
SN - 2152-5250
IS - 6
ER -