Abstract
In the ischemic brain, reperfusion with tissue plasminogen activator (tPA) sometimes causes catastrophic hemorrhagic transformation (HT); however, the mechanism remains elusive. Here, we show that the basement membrane, and not the endothelial cells, is vulnerable to ischemic/reperfusion injury with tPA treatment. We treated a spontaneously hypertensive rat model of middle cerebral artery occlusion (MCAO) with vehicle alone, tPA alone, or a free radical scavenger, edaravone, plus tPA. Light and electron microscopic analyses of each microvascular component revealed that the basement membrane disintegrated and became detached from the astrocyte endfeet in tPA-treated animals that showed HT. On the other hand, edaravone prevented the dissociation of the neurovascular unit, dramatically decreased the HT, and improved the neurologic score and survival rate of the tPA-treated rats. These results suggest that the basement membrane that underlies the endothelial cells is a key structure for maintaining the integrity of the neurovascular unit, and a free-radical scavenger can be a viable agent for inhibiting tPA-induced HT.
| Original language | English |
|---|---|
| Pages (from-to) | 715-725 |
| Number of pages | 11 |
| Journal | Journal of Cerebral Blood Flow and Metabolism |
| Volume | 29 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 2009 |
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Keywords
- Cerebral ischemia
- Hemorrhagic transformation
- Ischemia/reperfusion injury
- Plasminogen activators
- Thrombolysis
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Clinical Neurology
- Neurology
Cite this
Dissociation and protection of the neurovascular unit after thrombolysis and reperfusion in ischemic rat brain. / Yamashita, Toru; Kamiya, Tatsushi; Deguchi, Kentaro; Inaba, Toshiki; Zhang, Hanzhe; Shang, Jingwei; Miyazaki, Kazunori; Ohtsuka, Aiji; Katayama, Yasuo; Abe, Koji.
In: Journal of Cerebral Blood Flow and Metabolism, Vol. 29, No. 4, 04.2009, p. 715-725.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Dissociation and protection of the neurovascular unit after thrombolysis and reperfusion in ischemic rat brain
AU - Yamashita, Toru
AU - Kamiya, Tatsushi
AU - Deguchi, Kentaro
AU - Inaba, Toshiki
AU - Zhang, Hanzhe
AU - Shang, Jingwei
AU - Miyazaki, Kazunori
AU - Ohtsuka, Aiji
AU - Katayama, Yasuo
AU - Abe, Koji
PY - 2009/4
Y1 - 2009/4
N2 - In the ischemic brain, reperfusion with tissue plasminogen activator (tPA) sometimes causes catastrophic hemorrhagic transformation (HT); however, the mechanism remains elusive. Here, we show that the basement membrane, and not the endothelial cells, is vulnerable to ischemic/reperfusion injury with tPA treatment. We treated a spontaneously hypertensive rat model of middle cerebral artery occlusion (MCAO) with vehicle alone, tPA alone, or a free radical scavenger, edaravone, plus tPA. Light and electron microscopic analyses of each microvascular component revealed that the basement membrane disintegrated and became detached from the astrocyte endfeet in tPA-treated animals that showed HT. On the other hand, edaravone prevented the dissociation of the neurovascular unit, dramatically decreased the HT, and improved the neurologic score and survival rate of the tPA-treated rats. These results suggest that the basement membrane that underlies the endothelial cells is a key structure for maintaining the integrity of the neurovascular unit, and a free-radical scavenger can be a viable agent for inhibiting tPA-induced HT.
AB - In the ischemic brain, reperfusion with tissue plasminogen activator (tPA) sometimes causes catastrophic hemorrhagic transformation (HT); however, the mechanism remains elusive. Here, we show that the basement membrane, and not the endothelial cells, is vulnerable to ischemic/reperfusion injury with tPA treatment. We treated a spontaneously hypertensive rat model of middle cerebral artery occlusion (MCAO) with vehicle alone, tPA alone, or a free radical scavenger, edaravone, plus tPA. Light and electron microscopic analyses of each microvascular component revealed that the basement membrane disintegrated and became detached from the astrocyte endfeet in tPA-treated animals that showed HT. On the other hand, edaravone prevented the dissociation of the neurovascular unit, dramatically decreased the HT, and improved the neurologic score and survival rate of the tPA-treated rats. These results suggest that the basement membrane that underlies the endothelial cells is a key structure for maintaining the integrity of the neurovascular unit, and a free-radical scavenger can be a viable agent for inhibiting tPA-induced HT.
KW - Cerebral ischemia
KW - Hemorrhagic transformation
KW - Ischemia/reperfusion injury
KW - Plasminogen activators
KW - Thrombolysis
UR - http://www.scopus.com/inward/record.url?scp=63949085383&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=63949085383&partnerID=8YFLogxK
U2 - 10.1038/jcbfm.2008.164
DO - 10.1038/jcbfm.2008.164
M3 - Article
C2 - 19142198
AN - SCOPUS:63949085383
VL - 29
SP - 715
EP - 725
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
SN - 0271-678X
IS - 4
ER -