{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:27:21Z","timestamp":1788787641202,"version":"build-2803163510"},"reference-count":89,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,11,27]],"date-time":"2020-11-27T00:00:00Z","timestamp":1606435200000},"content-version":"vor","delay-in-days":331,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"the Swedish Science Research Council","award":["Grants K2014-62X-12190-19-5 and 2019-01771-3"],"award-info":[{"award-number":["Grants K2014-62X-12190-19-5 and 2019-01771-3"]}]},{"name":"the National Science Center, Poland, within a framework of doctoral scholarship","award":["DEC-2015\/16\/T\/NZ7\/00171"],"award-info":[{"award-number":["DEC-2015\/16\/T\/NZ7\/00171"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Unilateral traumatic brain injury and stroke result in asymmetric postural and motor deficits including contralateral hemiplegia and hemiparesis. In animals, a localized unilateral brain injury recapitulates the human upper motor neuron syndrome in the formation of hindlimb postural asymmetry with contralesional limb flexion and the asymmetry of hindlimb nociceptive withdrawal reflexes. The current view is that these effects are developed due to aberrant activity of motor pathways that descend from the brain into the spinal cord. These pathways and their target spinal circuits may be regulated by local neurohormonal systems that may also mediate effects of brain injury. Here, we evaluate if a unilateral traumatic brain injury induces hindlimb postural asymmetry, a model of postural deficits, and if this asymmetry is spinally encoded and mediated by the endogenous opioid system in rats. A unilateral right-sided controlled cortical impact, a model of clinical focal traumatic brain injury was centred over the sensorimotor cortex and was observed to induce hindlimb postural asymmetry with contralateral limb flexion. The asymmetry persisted after complete spinal cord transection, implicating local neurocircuitry in the development of the deficits. Administration of the general opioid antagonist naloxone and \u03bc-antagonist \u03b2-funaltrexamine blocked the formation of postural asymmetry. Surprisingly, \u03ba-antagonists nor-binaltorphimine and LY2444296 did not affect the asymmetry magnitude but reversed the flexion side; instead of contralesional (left) hindlimb flexion the ipsilesional (right) limb was flexed. The postural effects of the right-side cortical injury were mimicked in animals with intact brain via intrathecal administration of the opioid \u03ba-agonist (2)-(trans)-3,4-Dichloro-N-methyl-N-[2-(1-pyrrolidiny)-cyclohexyl]benzeneacetamide that induced hindlimb postural asymmetry with left limb flexion. The \u03b4-antagonist naltrindole produced no effect on the contralesional (left) flexion but inhibited the formation of the ipsilesional (right) limb flexion in brain-injured rats that were treated with \u03ba-antagonist. The effects of the antagonists were evident before and after spinal cord transection. We concluded that the focal traumatic brain injury-induced postural asymmetry was encoded at the spinal level, and was blocked or its side was reversed by administration of opioid antagonists. The findings suggest that the balance in activity of the mirror symmetric spinal neural circuits regulating contraction of the left and right hindlimb muscles is controlled by different subtypes of opioid receptors; and that this equilibrium is impaired after unilateral brain trauma through side-specific opioid mechanism.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaa208","type":"journal-article","created":{"date-parts":[[2020,11,27]],"date-time":"2020-11-27T09:36:50Z","timestamp":1606469810000},"source":"Crossref","is-referenced-by-count":22,"title":["Ipsilesional<i>versus<\/i>contralesional postural deficits induced by unilateral brain trauma: a side reversal by opioid mechanism"],"prefix":"10.1093","volume":"2","author":[{"given":"Hiroyuki","family":"Watanabe","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Nosova","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniil","family":"Sarkisyan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlene Storm","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5945-6625","authenticated-orcid":false,"given":"Mengliang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark"},{"name":"Department of Experimental Medical Science, Neuronano Research Center, Lund University, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Rorick-Kehn","sequence":"additional","affiliation":[{"name":"Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik","family":"Clausen","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Neurosurgery, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinga","family":"Gawel","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, Medical University of Lublin, Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Kehr","sequence":"additional","affiliation":[{"name":"Department of Physiology, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Hallberg","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Schouenborg","sequence":"additional","affiliation":[{"name":"Department of Experimental Medical Science, Neuronano Research Center, Lund University, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niklas","family":"Marklund","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Neurosurgery, Uppsala University, Uppsala, Sweden"},{"name":"Lund University, Skane University Hospital, Department of Clinical Sciences Lund, Neurosurgery, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgy","family":"Bakalkin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,12,13]]},"reference":[{"key":"2021061905592020200_fcaa208-B1","first-page":"1271","article-title":"Postural asymmetry induction by factors of the right and left hemispheres","volume":"260","author":"Bakalkin","year":"1981","journal-title":"Dokl Akad Nauk Sssr"},{"key":"2021061905592020200_fcaa208-B2","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/0006-8993(89)90193-5","article-title":"Opioids induce postural asymmetry in spinal rat: the side of the flexed limb depends upon the type of opioid agonist","volume":"480","author":"Bakalkin","year":"1989","journal-title":"Brain 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