Negative Allosteric Modulator of mGluR1 Improves Long-Term Neurologic Deficits after Experimental Subarachnoid Hemorrhage
Aneurysmal subarachnoid hemorrhage (SAH) causes permanent neurological sequelae, but the underlying mechanism needs to be further clarified. Here, we show that inhibition of metabotropic glutamate receptor 1 (mGluR1) with negative allosteric modulator JNJ16259685 improves long-term neurobehavioral outcomes in an endovascular perforation model of SAH. JNJ16259685 improves cerebrovascular dysfunction through attenuation of cerebral blood flow (CBF) reduction, cerebral vasoconstrictio, and microthrombosis formation in a rat SAH model. Moreover, JNJ16259685 reduces experimental SAH-induced long-term neuronal damage through alleviation of neuronal death and degeneration. Mechanically, JNJ16259685 maintains phosphorylation of endothelial NO synthase (eNOS) and vasodilator-stimulated phosphoprotein (VASP) and decreases apoptosis-related factors Bax, active caspase-9, and active caspase-3 following experimental SAH. Altogether, our results suggest JNJ16259685 improves long-term functional impairment through neurovascular protection.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
ACS chemical neuroscience - 11(2020), 18 vom: 16. Sept., Seite 2869-2880 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Hong-Bin [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 18.06.2021 Date Revised 18.06.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/acschemneuro.0c00485 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM313610401 |
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| 245 | 1 | 0 | |a Negative Allosteric Modulator of mGluR1 Improves Long-Term Neurologic Deficits after Experimental Subarachnoid Hemorrhage |
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| 500 | |a Date Revised 18.06.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Aneurysmal subarachnoid hemorrhage (SAH) causes permanent neurological sequelae, but the underlying mechanism needs to be further clarified. Here, we show that inhibition of metabotropic glutamate receptor 1 (mGluR1) with negative allosteric modulator JNJ16259685 improves long-term neurobehavioral outcomes in an endovascular perforation model of SAH. JNJ16259685 improves cerebrovascular dysfunction through attenuation of cerebral blood flow (CBF) reduction, cerebral vasoconstrictio, and microthrombosis formation in a rat SAH model. Moreover, JNJ16259685 reduces experimental SAH-induced long-term neuronal damage through alleviation of neuronal death and degeneration. Mechanically, JNJ16259685 maintains phosphorylation of endothelial NO synthase (eNOS) and vasodilator-stimulated phosphoprotein (VASP) and decreases apoptosis-related factors Bax, active caspase-9, and active caspase-3 following experimental SAH. Altogether, our results suggest JNJ16259685 improves long-term functional impairment through neurovascular protection | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Subarachnoid hemorrhage | |
| 650 | 4 | |a cerebral vasospasm | |
| 650 | 4 | |a long-term neurological deficits | |
| 650 | 4 | |a mGluR1 | |
| 650 | 4 | |a microthrombosis | |
| 650 | 7 | |a Receptors, Metabotropic Glutamate |2 NLM | |
| 650 | 7 | |a metabotropic glutamate receptor type 1 |2 NLM | |
| 700 | 1 | |a Wang, Wei-Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Qing-Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Hou, Ya-Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Han-Xia |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Hui-Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Ming-Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Bao-Liang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Zong-Yong |e verfasserin |4 aut | |
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