Optogenetic Stimulation Reduces Neuronal Nitric Oxide Synthase Expression After Stroke
Post-stroke optogenetic stimulation has been shown to enhance neurovascular coupling and functional recovery. Neuronal nitric oxide synthase (nNOS) has been implicated as a key regulator of the neurovascular response in acute stroke; however, its role in subacute recovery remains unclear. We investi...
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| Veröffentlicht in: | Translational stroke research 2021-04, Vol.12 (2), p.347-356 |
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| creator | Pendharkar, Arjun V. Smerin, Daniel Gonzalez, Lorenzo Wang, Eric H. Levy, Sabrina Wang, Stephanie Ishizaka, Shunsuke Ito, Masaki Uchino, Haruto Chiang, Terrance Cheng, Michelle Y. Steinberg, Gary K. |
| description | Post-stroke optogenetic stimulation has been shown to enhance neurovascular coupling and functional recovery. Neuronal nitric oxide synthase (nNOS) has been implicated as a key regulator of the neurovascular response in acute stroke; however, its role in subacute recovery remains unclear. We investigated the expression of nNOS in stroke mice undergoing optogenetic stimulation of the contralesional lateral cerebellar nucleus (cLCN). We also examined the effects of nNOS inhibition on functional recovery using a pharmacological inhibitor targeting nNOS. Optogenetically stimulated stroke mice demonstrated significant improvement on the horizontal rotating beam task at post-stroke days 10 and 14. nNOS mRNA and protein expression was significantly and selectively decreased in the contralesional primary motor cortex (cM1) of cLCN-stimulated mice. The nNOS expression in cM1 was negatively correlated with improved recovery. nNOS inhibitor (ARL 17477)-treated stroke mice exhibited a significant functional improvement in speed at post-stroke day 10, when compared to stroke mice receiving vehicle (saline) only. Our results show that optogenetic stimulation of cLCN and systemic nNOS inhibition both produce functional benefits after stroke, and suggest that nNOS may play a maladaptive role in post-stroke recovery. |
| doi_str_mv | 10.1007/s12975-020-00831-y |
| format | Article |
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Neuronal nitric oxide synthase (nNOS) has been implicated as a key regulator of the neurovascular response in acute stroke; however, its role in subacute recovery remains unclear. We investigated the expression of nNOS in stroke mice undergoing optogenetic stimulation of the contralesional lateral cerebellar nucleus (cLCN). We also examined the effects of nNOS inhibition on functional recovery using a pharmacological inhibitor targeting nNOS. Optogenetically stimulated stroke mice demonstrated significant improvement on the horizontal rotating beam task at post-stroke days 10 and 14. nNOS mRNA and protein expression was significantly and selectively decreased in the contralesional primary motor cortex (cM1) of cLCN-stimulated mice. The nNOS expression in cM1 was negatively correlated with improved recovery. nNOS inhibitor (ARL 17477)-treated stroke mice exhibited a significant functional improvement in speed at post-stroke day 10, when compared to stroke mice receiving vehicle (saline) only. Our results show that optogenetic stimulation of cLCN and systemic nNOS inhibition both produce functional benefits after stroke, and suggest that nNOS may play a maladaptive role in post-stroke recovery.</description><identifier>ISSN: 1868-4483</identifier><identifier>EISSN: 1868-601X</identifier><identifier>DOI: 10.1007/s12975-020-00831-y</identifier><identifier>PMID: 32661768</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Animals ; Behavior ; Biomedical and Life Sciences ; Biomedicine ; Body temperature ; Cardiology ; Carotid arteries ; Heart rate ; Ischemia ; Lasers ; Mice ; Neurology ; Neurons ; Neurosciences ; Neurosurgery ; Nitric Oxide ; Nitric Oxide Synthase Type I - genetics ; Optogenetics ; Original ; Original Article ; Physiology ; Recovery of Function ; Respiration ; Stroke - therapy ; Surgery ; Vascular Surgery ; Veins & arteries</subject><ispartof>Translational stroke research, 2021-04, Vol.12 (2), p.347-356</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-b94627b61538dcc197930acc8e341f1e568a0df507bea291e4a6ebe2785775ba3</citedby><cites>FETCH-LOGICAL-c540t-b94627b61538dcc197930acc8e341f1e568a0df507bea291e4a6ebe2785775ba3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12975-020-00831-y$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2920227027?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>230,314,780,784,885,21388,21389,27924,27925,33530,33531,33744,33745,41488,42557,43659,43805,51319,64385,64387,64389,72469</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32661768$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pendharkar, Arjun V.</creatorcontrib><creatorcontrib>Smerin, Daniel</creatorcontrib><creatorcontrib>Gonzalez, Lorenzo</creatorcontrib><creatorcontrib>Wang, Eric H.</creatorcontrib><creatorcontrib>Levy, Sabrina</creatorcontrib><creatorcontrib>Wang, Stephanie</creatorcontrib><creatorcontrib>Ishizaka, Shunsuke</creatorcontrib><creatorcontrib>Ito, Masaki</creatorcontrib><creatorcontrib>Uchino, Haruto</creatorcontrib><creatorcontrib>Chiang, Terrance</creatorcontrib><creatorcontrib>Cheng, Michelle Y.</creatorcontrib><creatorcontrib>Steinberg, Gary K.</creatorcontrib><title>Optogenetic Stimulation Reduces Neuronal Nitric Oxide Synthase Expression After Stroke</title><title>Translational stroke research</title><addtitle>Transl. Stroke Res</addtitle><addtitle>Transl Stroke Res</addtitle><description>Post-stroke optogenetic stimulation has been shown to enhance neurovascular coupling and functional recovery. Neuronal nitric oxide synthase (nNOS) has been implicated as a key regulator of the neurovascular response in acute stroke; however, its role in subacute recovery remains unclear. We investigated the expression of nNOS in stroke mice undergoing optogenetic stimulation of the contralesional lateral cerebellar nucleus (cLCN). We also examined the effects of nNOS inhibition on functional recovery using a pharmacological inhibitor targeting nNOS. Optogenetically stimulated stroke mice demonstrated significant improvement on the horizontal rotating beam task at post-stroke days 10 and 14. nNOS mRNA and protein expression was significantly and selectively decreased in the contralesional primary motor cortex (cM1) of cLCN-stimulated mice. The nNOS expression in cM1 was negatively correlated with improved recovery. nNOS inhibitor (ARL 17477)-treated stroke mice exhibited a significant functional improvement in speed at post-stroke day 10, when compared to stroke mice receiving vehicle (saline) only. Our results show that optogenetic stimulation of cLCN and systemic nNOS inhibition both produce functional benefits after stroke, and suggest that nNOS may play a maladaptive role in post-stroke recovery.</description><subject>Animals</subject><subject>Behavior</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Body temperature</subject><subject>Cardiology</subject><subject>Carotid arteries</subject><subject>Heart rate</subject><subject>Ischemia</subject><subject>Lasers</subject><subject>Mice</subject><subject>Neurology</subject><subject>Neurons</subject><subject>Neurosciences</subject><subject>Neurosurgery</subject><subject>Nitric Oxide</subject><subject>Nitric Oxide Synthase Type I - genetics</subject><subject>Optogenetics</subject><subject>Original</subject><subject>Original Article</subject><subject>Physiology</subject><subject>Recovery of Function</subject><subject>Respiration</subject><subject>Stroke - therapy</subject><subject>Surgery</subject><subject>Vascular Surgery</subject><subject>Veins & arteries</subject><issn>1868-4483</issn><issn>1868-601X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kU1v1DAQhi0EolXpH-CAInHhEhh_xHYuSFVVClLVlSggbpbjTLYu2XixHdT99_WyS4Ee6ostzTPP2H4JeUnhLQVQ7xJlrWpqYFADaE7rzRNySLXUtQT6_en-LITmB-Q4pRsoi1MhBX9ODjiTkiqpD8m3xTqHJU6Yvauusl_No80-TNVn7GeHqbrEOYbJjtWlz7Ewi1vfY3W1mfK1TVid3a4jprTtOBkyxuKI4Qe-IM8GOyY83u9H5OuHsy-nH-uLxfmn05OL2jUCct21QjLVSdpw3TtHW9VysM5p5IIOFBupLfRDA6pDy1qKwkrskCndKNV0lh-R9zvveu5W2DuccrSjWUe_snFjgvXm_8rkr80y_DKqZY3Qqgje7AUx_JwxZbPyyeE42gnDnAwTjGugElhBXz9Ab8Icy9cUqmXAmAK2FbId5WJIKeJwfxkKZpuc2SVnSnLmd3JmU5pe_fuM-5Y_ORWA74BUStMS49_Zj2jvALvjpac</recordid><startdate>20210401</startdate><enddate>20210401</enddate><creator>Pendharkar, Arjun V.</creator><creator>Smerin, Daniel</creator><creator>Gonzalez, Lorenzo</creator><creator>Wang, Eric H.</creator><creator>Levy, Sabrina</creator><creator>Wang, Stephanie</creator><creator>Ishizaka, Shunsuke</creator><creator>Ito, Masaki</creator><creator>Uchino, Haruto</creator><creator>Chiang, Terrance</creator><creator>Cheng, Michelle Y.</creator><creator>Steinberg, Gary K.</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20210401</creationdate><title>Optogenetic Stimulation Reduces Neuronal Nitric Oxide Synthase Expression After Stroke</title><author>Pendharkar, Arjun V. ; 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Stroke Res</stitle><addtitle>Transl Stroke Res</addtitle><date>2021-04-01</date><risdate>2021</risdate><volume>12</volume><issue>2</issue><spage>347</spage><epage>356</epage><pages>347-356</pages><issn>1868-4483</issn><eissn>1868-601X</eissn><abstract>Post-stroke optogenetic stimulation has been shown to enhance neurovascular coupling and functional recovery. Neuronal nitric oxide synthase (nNOS) has been implicated as a key regulator of the neurovascular response in acute stroke; however, its role in subacute recovery remains unclear. We investigated the expression of nNOS in stroke mice undergoing optogenetic stimulation of the contralesional lateral cerebellar nucleus (cLCN). We also examined the effects of nNOS inhibition on functional recovery using a pharmacological inhibitor targeting nNOS. Optogenetically stimulated stroke mice demonstrated significant improvement on the horizontal rotating beam task at post-stroke days 10 and 14. nNOS mRNA and protein expression was significantly and selectively decreased in the contralesional primary motor cortex (cM1) of cLCN-stimulated mice. The nNOS expression in cM1 was negatively correlated with improved recovery. nNOS inhibitor (ARL 17477)-treated stroke mice exhibited a significant functional improvement in speed at post-stroke day 10, when compared to stroke mice receiving vehicle (saline) only. Our results show that optogenetic stimulation of cLCN and systemic nNOS inhibition both produce functional benefits after stroke, and suggest that nNOS may play a maladaptive role in post-stroke recovery.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>32661768</pmid><doi>10.1007/s12975-020-00831-y</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Behavior Biomedical and Life Sciences Biomedicine Body temperature Cardiology Carotid arteries Heart rate Ischemia Lasers Mice Neurology Neurons Neurosciences Neurosurgery Nitric Oxide Nitric Oxide Synthase Type I - genetics Optogenetics Original Original Article Physiology Recovery of Function Respiration Stroke - therapy Surgery Vascular Surgery Veins & arteries |
| title | Optogenetic Stimulation Reduces Neuronal Nitric Oxide Synthase Expression After Stroke |
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