{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:09:25Z","timestamp":1787317765798,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,1,23]],"date-time":"2015-01-23T00:00:00Z","timestamp":1421971200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["NS 43285"],"award-info":[{"award-number":["NS 43285"]}]},{"name":"NIH","award":["NS051402"],"award-info":[{"award-number":["NS051402"]}]},{"name":"FAPESP S\u00e3o Paulo Research Foundation, Brazil"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    We hypothesized that a deficiency in the descending serotonergic input to spinal cord may underlie postnatal muscle hypertonia after global antenatal hypoxic\u2010ischemic injury in a rabbit model of cerebral palsy. Neurotransmitter content was determined by\n                    <jats:styled-content style=\"fixed-case\">HPLC<\/jats:styled-content>\n                    in the spinal cord of newborns with and without muscle hypertonia after fetal global hypoxic\u2010ischemic brain injury and na\u00efve controls. Contrary to our hypothesis, serotonin levels in both cervical and lumbar expansions and norepinephrine in cervical expansion were increased in hypertonic kits relative to non\u2010hypertonic kits and controls, with unchanged number of serotonergic cells in caudal raphe by stereological count. Serotonergic fiber length per unit of volume was also increased in hypertonic kits\u2019 cervical and lumbar spinal cord, both in dorsal and ventral horns. Gene expression of serotonin transporter was increased and 5\u2010\n                    <jats:styled-content style=\"fixed-case\">HTR<\/jats:styled-content>\n                    <jats:sub>2<\/jats:sub>\n                    receptors were decreased in hypertonic kits relative to controls in cervical and lumbar cord. Intrathecal administration of non\u2010selective serotonin receptor inhibitor methysergide decreased muscle tone in hypertonic kits only. Conversely, intrathecal administration of serotonin solution increased muscle tone only in non\u2010hypertonic kits. We speculate that maturation of serotonergic system in spinal cord may be directly affected by decreased corticospinal connectivity after antenatal hypoxic\u2010ischemic brain injury.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc12997-fig-0009-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>\n                  <jats:p>Following prenatal hypoxia\u2013ischemia, newborn rabbits exhibit elevated levels of serotonin in the spinal cord that were linked to muscle hypertonia. Serotonergic terminal density was also increased in hypertonic newborns\u2019 spinal cord. Intrathecal administration of the non\u2010selective serotonin receptor inhibitor methysergide decreased muscle tone in hypertonic newborns only. Elevated spinal serotonin thus suggests a novel pathophysiological mechanism of hypertonia in cerebral palsy.<\/jats:p>","DOI":"10.1111\/jnc.12997","type":"journal-article","created":{"date-parts":[[2014,11,25]],"date-time":"2014-11-25T01:49:52Z","timestamp":1416880192000},"page":"394-402","source":"Crossref","is-referenced-by-count":14,"title":["Elevated spinal monoamine neurotransmitters after antenatal hypoxia\u2013ischemia in rabbit cerebral palsy model"],"prefix":"10.1111","volume":"132","author":[{"given":"Alexander","family":"Drobyshevsky","sequence":"first","affiliation":[{"name":"Department of Pediatrics, NorthShore University HealthSystem Evanston and University of Chicago Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia Honda","family":"Takada","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology Institute of Biomedical Sciences Universidade de S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kehuan","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, NorthShore University HealthSystem Evanston and University of Chicago Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Derrick","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, NorthShore University HealthSystem Evanston and University of Chicago Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, NorthShore University HealthSystem Evanston and University of Chicago Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina A.","family":"Quinlan","sequence":"additional","affiliation":[{"name":"Department of Physiology Feinberg School of Medicine Northwestern University Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeannette","family":"Vasquez\u2010Vivar","sequence":"additional","affiliation":[{"name":"Department of Biophysics Medical College of Wisconsin Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria In\u00eas","family":"Nogueira","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology Institute of Biomedical Sciences Universidade de S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidhartha","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, NorthShore University HealthSystem Evanston and University of Chicago Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,1,23]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"42","article-title":"Deficits of brainstem and spinal cord functions after neonatal hypoxia\u2010ischemia in mice","volume":"11","author":"Bellot B.","year":"2014","journal-title":"Pediatr. 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