An Automated Test of Rat Forelimb Supination Quantifies Motor Function Loss and Recovery After Corticospinal Injury

Background. Rodents are the primary animal model of corticospinal injury and repair, yet current behavioral tests do not show the large deficits after injury observed in humans. Forearm supination is critical for hand function and is highly impaired by corticospinal injury in both humans and rats. C...

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Veröffentlicht in:Neurorehabilitation and neural repair 2017-02, Vol.31 (2), p.122-132
Hauptverfasser: Sindhurakar, Anil, Butensky, Samuel D., Meyers, Eric, Santos, Joshua, Bethea, Thelma, Khalili, Ashley, Sloan, Andrew P., Rennaker, Robert L., Carmel, Jason B.
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container_end_page 132
container_issue 2
container_start_page 122
container_title Neurorehabilitation and neural repair
container_volume 31
creator Sindhurakar, Anil
Butensky, Samuel D.
Meyers, Eric
Santos, Joshua
Bethea, Thelma
Khalili, Ashley
Sloan, Andrew P.
Rennaker, Robert L.
Carmel, Jason B.
description Background. Rodents are the primary animal model of corticospinal injury and repair, yet current behavioral tests do not show the large deficits after injury observed in humans. Forearm supination is critical for hand function and is highly impaired by corticospinal injury in both humans and rats. Current tests of rodent forelimb function do not measure this movement. Objective. To determine if quantification of forelimb supination in rats reveals large-scale functional loss and partial recovery after corticospinal injury. Methods. We developed a knob supination device that quantifies supination using automated and objective methods. Rats in a reaching box have to grasp and turn a knob in supination in order to receive a food reward. Performance on this task and the single pellet reaching task were measured before and after 2 manipulations of the pyramidal tract: a cut lesion of 1 pyramid and inactivation of motor cortex using 2 different drug doses. Results. A cut lesion of the corticospinal tract produced a large deficit in supination. In contrast, there was no change in pellet retrieval success. Supination function recovered partially over 6 weeks after injury, and a large deficit remained. Motor cortex inactivation produced a dose-dependent loss of knob supination; the effect on pellet reaching was more subtle. Conclusions. The knob supination task reveals in rodents 3 signature hand function changes observed in humans with corticospinal injury: (1) large-scale loss with injury, (2) partial recovery in the weeks after injury, and (3) loss proportional to degree of dysfunction.
doi_str_mv 10.1177/1545968316662528
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Rodents are the primary animal model of corticospinal injury and repair, yet current behavioral tests do not show the large deficits after injury observed in humans. Forearm supination is critical for hand function and is highly impaired by corticospinal injury in both humans and rats. Current tests of rodent forelimb function do not measure this movement. Objective. To determine if quantification of forelimb supination in rats reveals large-scale functional loss and partial recovery after corticospinal injury. Methods. We developed a knob supination device that quantifies supination using automated and objective methods. Rats in a reaching box have to grasp and turn a knob in supination in order to receive a food reward. Performance on this task and the single pellet reaching task were measured before and after 2 manipulations of the pyramidal tract: a cut lesion of 1 pyramid and inactivation of motor cortex using 2 different drug doses. Results. A cut lesion of the corticospinal tract produced a large deficit in supination. In contrast, there was no change in pellet retrieval success. Supination function recovered partially over 6 weeks after injury, and a large deficit remained. Motor cortex inactivation produced a dose-dependent loss of knob supination; the effect on pellet reaching was more subtle. Conclusions. The knob supination task reveals in rodents 3 signature hand function changes observed in humans with corticospinal injury: (1) large-scale loss with injury, (2) partial recovery in the weeks after injury, and (3) loss proportional to degree of dysfunction.</description><identifier>ISSN: 1545-9683</identifier><identifier>EISSN: 1552-6844</identifier><identifier>DOI: 10.1177/1545968316662528</identifier><identifier>PMID: 27530125</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Animals ; Automation, Laboratory ; Disease Models, Animal ; Equipment Design ; Female ; Food ; Forelimb - physiopathology ; Motor Cortex - injuries ; Motor Cortex - physiopathology ; Motor Skills ; Movement Disorders - diagnosis ; Movement Disorders - etiology ; Movement Disorders - physiopathology ; Muscimol ; Pyramidal Tracts - injuries ; Pyramidal Tracts - physiopathology ; Rats, Sprague-Dawley ; Recovery of Function ; Severity of Illness Index ; Spinal Cord Injuries - complications ; Spinal Cord Injuries - diagnosis ; Spinal Cord Injuries - physiopathology ; Supination</subject><ispartof>Neurorehabilitation and neural repair, 2017-02, Vol.31 (2), p.122-132</ispartof><rights>The Author(s) 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c434t-4f53f802ca09887d20c9a98ce4059e8c1ef29bdb500b304038cce1f0e5c7ba373</citedby><cites>FETCH-LOGICAL-c434t-4f53f802ca09887d20c9a98ce4059e8c1ef29bdb500b304038cce1f0e5c7ba373</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/1545968316662528$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/1545968316662528$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>230,314,776,780,881,21799,27903,27904,43600,43601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27530125$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sindhurakar, Anil</creatorcontrib><creatorcontrib>Butensky, Samuel D.</creatorcontrib><creatorcontrib>Meyers, Eric</creatorcontrib><creatorcontrib>Santos, Joshua</creatorcontrib><creatorcontrib>Bethea, Thelma</creatorcontrib><creatorcontrib>Khalili, Ashley</creatorcontrib><creatorcontrib>Sloan, Andrew P.</creatorcontrib><creatorcontrib>Rennaker, Robert L.</creatorcontrib><creatorcontrib>Carmel, Jason B.</creatorcontrib><title>An Automated Test of Rat Forelimb Supination Quantifies Motor Function Loss and Recovery After Corticospinal Injury</title><title>Neurorehabilitation and neural repair</title><addtitle>Neurorehabil Neural Repair</addtitle><description>Background. Rodents are the primary animal model of corticospinal injury and repair, yet current behavioral tests do not show the large deficits after injury observed in humans. Forearm supination is critical for hand function and is highly impaired by corticospinal injury in both humans and rats. Current tests of rodent forelimb function do not measure this movement. Objective. To determine if quantification of forelimb supination in rats reveals large-scale functional loss and partial recovery after corticospinal injury. Methods. We developed a knob supination device that quantifies supination using automated and objective methods. Rats in a reaching box have to grasp and turn a knob in supination in order to receive a food reward. Performance on this task and the single pellet reaching task were measured before and after 2 manipulations of the pyramidal tract: a cut lesion of 1 pyramid and inactivation of motor cortex using 2 different drug doses. Results. A cut lesion of the corticospinal tract produced a large deficit in supination. In contrast, there was no change in pellet retrieval success. Supination function recovered partially over 6 weeks after injury, and a large deficit remained. Motor cortex inactivation produced a dose-dependent loss of knob supination; the effect on pellet reaching was more subtle. Conclusions. The knob supination task reveals in rodents 3 signature hand function changes observed in humans with corticospinal injury: (1) large-scale loss with injury, (2) partial recovery in the weeks after injury, and (3) loss proportional to degree of dysfunction.</description><subject>Animals</subject><subject>Automation, Laboratory</subject><subject>Disease Models, Animal</subject><subject>Equipment Design</subject><subject>Female</subject><subject>Food</subject><subject>Forelimb - physiopathology</subject><subject>Motor Cortex - injuries</subject><subject>Motor Cortex - physiopathology</subject><subject>Motor Skills</subject><subject>Movement Disorders - diagnosis</subject><subject>Movement Disorders - etiology</subject><subject>Movement Disorders - physiopathology</subject><subject>Muscimol</subject><subject>Pyramidal Tracts - injuries</subject><subject>Pyramidal Tracts - physiopathology</subject><subject>Rats, Sprague-Dawley</subject><subject>Recovery of Function</subject><subject>Severity of Illness Index</subject><subject>Spinal Cord Injuries - complications</subject><subject>Spinal Cord Injuries - diagnosis</subject><subject>Spinal Cord Injuries - physiopathology</subject><subject>Supination</subject><issn>1545-9683</issn><issn>1552-6844</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kUuLFDEUhYMozkP3riRLN6V5VqU2QtPYOtAijuM6pFI3Y5qqpM1joP-91fbMoIKrGzjnfjecg9ArSt5S2nXvqBSybxWnbdsyydQTdE6lZE2rhHh6fAvZHPUzdJHzjhDGVU-eozPWSU4ok-corwJe1RJnU2DEN5ALjg5fm4I3McHk5wF_q3sfTPEx4K_VhOKdh4w_xxIT3tRgfyvbmDM2YcTXYOMdpANeuQIJr2Mq3sZ8REz4KuxqOrxAz5yZMry8n5fo--bDzfpTs_3y8Wq92jZWcFEa4SR3ijBrSK9UNzJie9MrC4LIHpSl4Fg_jIMkZOBEEK6sBeoISNsNhnf8Er0_cfd1mGG0EEoyk94nP5t00NF4_bcS_A99G--0ZIJTJRfAm3tAij_rko2efbYwTSZArFlTxaUkkkm1WMnJatOSRAL3eIYSfexK_9vVsvL6z-89LjyUsxiakyGbW9C7WNOSYf4_8BfwLZ5I</recordid><startdate>20170201</startdate><enddate>20170201</enddate><creator>Sindhurakar, Anil</creator><creator>Butensky, Samuel D.</creator><creator>Meyers, Eric</creator><creator>Santos, Joshua</creator><creator>Bethea, Thelma</creator><creator>Khalili, Ashley</creator><creator>Sloan, Andrew P.</creator><creator>Rennaker, Robert L.</creator><creator>Carmel, Jason B.</creator><general>SAGE Publications</general><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170201</creationdate><title>An Automated Test of Rat Forelimb Supination Quantifies Motor Function Loss and Recovery After Corticospinal Injury</title><author>Sindhurakar, Anil ; Butensky, Samuel D. ; Meyers, Eric ; Santos, Joshua ; Bethea, Thelma ; Khalili, Ashley ; Sloan, Andrew P. ; Rennaker, Robert L. ; Carmel, Jason B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c434t-4f53f802ca09887d20c9a98ce4059e8c1ef29bdb500b304038cce1f0e5c7ba373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Automation, Laboratory</topic><topic>Disease Models, Animal</topic><topic>Equipment Design</topic><topic>Female</topic><topic>Food</topic><topic>Forelimb - physiopathology</topic><topic>Motor Cortex - injuries</topic><topic>Motor Cortex - physiopathology</topic><topic>Motor Skills</topic><topic>Movement Disorders - diagnosis</topic><topic>Movement Disorders - etiology</topic><topic>Movement Disorders - physiopathology</topic><topic>Muscimol</topic><topic>Pyramidal Tracts - injuries</topic><topic>Pyramidal Tracts - physiopathology</topic><topic>Rats, Sprague-Dawley</topic><topic>Recovery of Function</topic><topic>Severity of Illness Index</topic><topic>Spinal Cord Injuries - complications</topic><topic>Spinal Cord Injuries - diagnosis</topic><topic>Spinal Cord Injuries - physiopathology</topic><topic>Supination</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sindhurakar, Anil</creatorcontrib><creatorcontrib>Butensky, Samuel D.</creatorcontrib><creatorcontrib>Meyers, Eric</creatorcontrib><creatorcontrib>Santos, Joshua</creatorcontrib><creatorcontrib>Bethea, Thelma</creatorcontrib><creatorcontrib>Khalili, Ashley</creatorcontrib><creatorcontrib>Sloan, Andrew P.</creatorcontrib><creatorcontrib>Rennaker, Robert L.</creatorcontrib><creatorcontrib>Carmel, Jason B.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Neurorehabilitation and neural repair</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sindhurakar, Anil</au><au>Butensky, Samuel D.</au><au>Meyers, Eric</au><au>Santos, Joshua</au><au>Bethea, Thelma</au><au>Khalili, Ashley</au><au>Sloan, Andrew P.</au><au>Rennaker, Robert L.</au><au>Carmel, Jason B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An Automated Test of Rat Forelimb Supination Quantifies Motor Function Loss and Recovery After Corticospinal Injury</atitle><jtitle>Neurorehabilitation and neural repair</jtitle><addtitle>Neurorehabil Neural Repair</addtitle><date>2017-02-01</date><risdate>2017</risdate><volume>31</volume><issue>2</issue><spage>122</spage><epage>132</epage><pages>122-132</pages><issn>1545-9683</issn><eissn>1552-6844</eissn><abstract>Background. Rodents are the primary animal model of corticospinal injury and repair, yet current behavioral tests do not show the large deficits after injury observed in humans. Forearm supination is critical for hand function and is highly impaired by corticospinal injury in both humans and rats. Current tests of rodent forelimb function do not measure this movement. Objective. To determine if quantification of forelimb supination in rats reveals large-scale functional loss and partial recovery after corticospinal injury. Methods. We developed a knob supination device that quantifies supination using automated and objective methods. Rats in a reaching box have to grasp and turn a knob in supination in order to receive a food reward. Performance on this task and the single pellet reaching task were measured before and after 2 manipulations of the pyramidal tract: a cut lesion of 1 pyramid and inactivation of motor cortex using 2 different drug doses. Results. A cut lesion of the corticospinal tract produced a large deficit in supination. In contrast, there was no change in pellet retrieval success. Supination function recovered partially over 6 weeks after injury, and a large deficit remained. Motor cortex inactivation produced a dose-dependent loss of knob supination; the effect on pellet reaching was more subtle. Conclusions. The knob supination task reveals in rodents 3 signature hand function changes observed in humans with corticospinal injury: (1) large-scale loss with injury, (2) partial recovery in the weeks after injury, and (3) loss proportional to degree of dysfunction.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>27530125</pmid><doi>10.1177/1545968316662528</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record>
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subjects Animals
Automation, Laboratory
Disease Models, Animal
Equipment Design
Female
Food
Forelimb - physiopathology
Motor Cortex - injuries
Motor Cortex - physiopathology
Motor Skills
Movement Disorders - diagnosis
Movement Disorders - etiology
Movement Disorders - physiopathology
Muscimol
Pyramidal Tracts - injuries
Pyramidal Tracts - physiopathology
Rats, Sprague-Dawley
Recovery of Function
Severity of Illness Index
Spinal Cord Injuries - complications
Spinal Cord Injuries - diagnosis
Spinal Cord Injuries - physiopathology
Supination
title An Automated Test of Rat Forelimb Supination Quantifies Motor Function Loss and Recovery After Corticospinal Injury
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