Anti-oxidative, anti-apoptotic, and pro-angiogenic effects mediate functional improvement by sonic hedgehog against focal cerebral ischemia in rats

Shiang Suo Huang; Henrich Cheng; Ching Min Tang; Mao Wei Nien; Yuahn Sieh Huang; I. Huei Lee; Jiu Haw Yin; Terry B.J. Kuo; Cheryl C.H. Yang; Shen Kou Tsai; Ding I. Yang

doi:10.1016/j.expneurol.2013.03.004

Anti-oxidative, anti-apoptotic, and pro-angiogenic effects mediate functional improvement by sonic hedgehog against focal cerebral ischemia in rats

Shiang Suo Huang, Henrich Cheng, Ching Min Tang, Mao Wei Nien, Yuahn Sieh Huang, I. Huei Lee, Jiu Haw Yin, Terry B.J. Kuo, Cheryl C.H. Yang, Shen Kou Tsai^*, Ding I. Yang

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摘要

Sonic hedgehog (SHH) is a morphogen important for neural development during embryogenesis. Recently, beneficial actions of SHH in ischemic injury have been noted. To test whether epidural application of the biolgically active N-terminal fragment of SHH (SHH-N) may reduce the extent of ischemic brain injury, male Long-Evans rats were exposed to a 60-min episode of middle cerebral artery occlusion (MCAO) with topical application of SHH-N and/or its specific inhibitor, cyclopamine, in fibrin glue over the peri-infarct cortex. We found that epidural application of SHH-N substaintially reduced infarct volumes after 7days of reperfusion, which was reversed by cyclopamine; SHH-N also improved behavioral outcomes as assessed by global neurological functions, rotarod test, and grasping power test. Furthermore, SHH-N attenuated the extents of protein oxidation, lipid peroxidation, and apoptosis induced by focal ischemia/reperfusion. Immunohistochemical staining coupled with bromodeoxyuridine (BrdU) incorporation revealed that SHH-N enhanced post-ischemic angiogenesis, stimulated the proliferation of nestin-positive (nestin⁺) neural progenitor cells (NPCs), and suppressed astrocytosis. Our results thus revealed multifaceted protective mechanisms of SHH-N against focal cerebral ischemia/reperfusion.

原文	English
頁（從 - 到）	680-688
頁數	9
期刊	Experimental Neurology
卷	247
DOIs	https://doi.org/10.1016/j.expneurol.2013.03.004
出版狀態	Published - 9月 2013

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10.1016/j.expneurol.2013.03.004

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Huang, S. S., Cheng, H., Tang, C. M., Nien, M. W., Huang, Y. S., Lee, I. H., Yin, J. H., Kuo, T. B. J., Yang, C. C. H., Tsai, S. K., & Yang, D. I. (2013). Anti-oxidative, anti-apoptotic, and pro-angiogenic effects mediate functional improvement by sonic hedgehog against focal cerebral ischemia in rats. Experimental Neurology, 247, 680-688. https://doi.org/10.1016/j.expneurol.2013.03.004

@article{aa837aef024b4b198391c5494626ce8c,

title = "Anti-oxidative, anti-apoptotic, and pro-angiogenic effects mediate functional improvement by sonic hedgehog against focal cerebral ischemia in rats",

abstract = "Sonic hedgehog (SHH) is a morphogen important for neural development during embryogenesis. Recently, beneficial actions of SHH in ischemic injury have been noted. To test whether epidural application of the biolgically active N-terminal fragment of SHH (SHH-N) may reduce the extent of ischemic brain injury, male Long-Evans rats were exposed to a 60-min episode of middle cerebral artery occlusion (MCAO) with topical application of SHH-N and/or its specific inhibitor, cyclopamine, in fibrin glue over the peri-infarct cortex. We found that epidural application of SHH-N substaintially reduced infarct volumes after 7days of reperfusion, which was reversed by cyclopamine; SHH-N also improved behavioral outcomes as assessed by global neurological functions, rotarod test, and grasping power test. Furthermore, SHH-N attenuated the extents of protein oxidation, lipid peroxidation, and apoptosis induced by focal ischemia/reperfusion. Immunohistochemical staining coupled with bromodeoxyuridine (BrdU) incorporation revealed that SHH-N enhanced post-ischemic angiogenesis, stimulated the proliferation of nestin-positive (nestin+) neural progenitor cells (NPCs), and suppressed astrocytosis. Our results thus revealed multifaceted protective mechanisms of SHH-N against focal cerebral ischemia/reperfusion.",

keywords = "Angiogenesis, Anti-apoptosis, Anti-oxidation, Focal ischemia, Middle cerebral artery occlusion",

author = "Huang, {Shiang Suo} and Henrich Cheng and Tang, {Ching Min} and Nien, {Mao Wei} and Huang, {Yuahn Sieh} and Lee, {I. Huei} and Yin, {Jiu Haw} and Kuo, {Terry B.J.} and Yang, {Cheryl C.H.} and Tsai, {Shen Kou} and Yang, {Ding I.}",

note = "Funding Information: We thank Miss Chun-Lien Chih for her excellent technical assistance in performing MCAO. This study was supported by the National Science Council in Taiwan ( NSC97-2314-B-010-008MY3 and NSC101-2314-B-010-042MY2 to Ding-I Yang, NSC98-2314-B-350-003-MY3 to Shen Kou Tsai, and NSC100-2320-B-040-007 to Shiang-Suo Huang), Ministry of Education in Taiwan-Aim for the Top University Plan ( 100A-C-B5 to Ding-I Yang), and Cheng Hsin General Hospital ( 101F195CY14 and 102F218C12 to Ding-I Yang and Jiu-Haw Yin).",

year = "2013",

month = sep,

doi = "10.1016/j.expneurol.2013.03.004",

language = "English",

volume = "247",

pages = "680--688",

journal = "Experimental Neurology",

issn = "0014-4886",

publisher = "Academic Press Inc.",

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T1 - Anti-oxidative, anti-apoptotic, and pro-angiogenic effects mediate functional improvement by sonic hedgehog against focal cerebral ischemia in rats

AU - Huang, Shiang Suo

AU - Cheng, Henrich

AU - Tang, Ching Min

AU - Nien, Mao Wei

AU - Huang, Yuahn Sieh

AU - Lee, I. Huei

AU - Yin, Jiu Haw

AU - Kuo, Terry B.J.

AU - Yang, Cheryl C.H.

AU - Tsai, Shen Kou

AU - Yang, Ding I.

N1 - Funding Information: We thank Miss Chun-Lien Chih for her excellent technical assistance in performing MCAO. This study was supported by the National Science Council in Taiwan ( NSC97-2314-B-010-008MY3 and NSC101-2314-B-010-042MY2 to Ding-I Yang, NSC98-2314-B-350-003-MY3 to Shen Kou Tsai, and NSC100-2320-B-040-007 to Shiang-Suo Huang), Ministry of Education in Taiwan-Aim for the Top University Plan ( 100A-C-B5 to Ding-I Yang), and Cheng Hsin General Hospital ( 101F195CY14 and 102F218C12 to Ding-I Yang and Jiu-Haw Yin).

PY - 2013/9

Y1 - 2013/9

N2 - Sonic hedgehog (SHH) is a morphogen important for neural development during embryogenesis. Recently, beneficial actions of SHH in ischemic injury have been noted. To test whether epidural application of the biolgically active N-terminal fragment of SHH (SHH-N) may reduce the extent of ischemic brain injury, male Long-Evans rats were exposed to a 60-min episode of middle cerebral artery occlusion (MCAO) with topical application of SHH-N and/or its specific inhibitor, cyclopamine, in fibrin glue over the peri-infarct cortex. We found that epidural application of SHH-N substaintially reduced infarct volumes after 7days of reperfusion, which was reversed by cyclopamine; SHH-N also improved behavioral outcomes as assessed by global neurological functions, rotarod test, and grasping power test. Furthermore, SHH-N attenuated the extents of protein oxidation, lipid peroxidation, and apoptosis induced by focal ischemia/reperfusion. Immunohistochemical staining coupled with bromodeoxyuridine (BrdU) incorporation revealed that SHH-N enhanced post-ischemic angiogenesis, stimulated the proliferation of nestin-positive (nestin+) neural progenitor cells (NPCs), and suppressed astrocytosis. Our results thus revealed multifaceted protective mechanisms of SHH-N against focal cerebral ischemia/reperfusion.

AB - Sonic hedgehog (SHH) is a morphogen important for neural development during embryogenesis. Recently, beneficial actions of SHH in ischemic injury have been noted. To test whether epidural application of the biolgically active N-terminal fragment of SHH (SHH-N) may reduce the extent of ischemic brain injury, male Long-Evans rats were exposed to a 60-min episode of middle cerebral artery occlusion (MCAO) with topical application of SHH-N and/or its specific inhibitor, cyclopamine, in fibrin glue over the peri-infarct cortex. We found that epidural application of SHH-N substaintially reduced infarct volumes after 7days of reperfusion, which was reversed by cyclopamine; SHH-N also improved behavioral outcomes as assessed by global neurological functions, rotarod test, and grasping power test. Furthermore, SHH-N attenuated the extents of protein oxidation, lipid peroxidation, and apoptosis induced by focal ischemia/reperfusion. Immunohistochemical staining coupled with bromodeoxyuridine (BrdU) incorporation revealed that SHH-N enhanced post-ischemic angiogenesis, stimulated the proliferation of nestin-positive (nestin+) neural progenitor cells (NPCs), and suppressed astrocytosis. Our results thus revealed multifaceted protective mechanisms of SHH-N against focal cerebral ischemia/reperfusion.

KW - Angiogenesis

KW - Anti-apoptosis

KW - Anti-oxidation

KW - Focal ischemia

KW - Middle cerebral artery occlusion

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U2 - 10.1016/j.expneurol.2013.03.004

DO - 10.1016/j.expneurol.2013.03.004

M3 - Article

C2 - 23499832

AN - SCOPUS:84881370807

SN - 0014-4886

VL - 247

SP - 680

EP - 688

JO - Experimental Neurology

JF - Experimental Neurology

ER -

Anti-oxidative, anti-apoptotic, and pro-angiogenic effects mediate functional improvement by sonic hedgehog against focal cerebral ischemia in rats

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