{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T09:51:13Z","timestamp":1781344273759,"version":"3.54.1"},"reference-count":15,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["PED"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:sec>\n<jats:title>OBJECTIVE<\/jats:title>\n<jats:p>Achondroplasia (ACH) is the most common short-limbed skeletal dysplasia caused by gain-of-function mutations in the fibroblast growth factor receptor 3 (<jats:italic>FGFR3<\/jats:italic>) gene. Foramen magnum stenosis (FMS) is one of the serious neurological complications in ACH. Through comprehensive drug screening, the authors identified that meclozine, an over-the-counter drug for motion sickness, inhibited activation of FGFR3 signaling. Oral administration of meclozine to the growing ACH mice promoted longitudinal bone growth, but it did not prevent FMS. In the current study, the authors evaluated the effects of maternal administration of meclozine on FMS in ACH mice.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>METHODS<\/jats:title>\n<jats:p>The area of the foramen magnum was measured in 17-day-old <jats:italic>Fgfr3<\/jats:italic><jats:sup>ach<\/jats:sup> mice and wild-type mice using micro-CT scanning. Meclozine was administered to the pregnant mice carrying <jats:italic>Fgfr3<\/jats:italic><jats:sup>ach<\/jats:sup> offspring from embryonic Day (ED) 14.5 to postnatal Day (PD) 4.5. Spheno-occipital and anterior intraoccipital synchondroses were histologically examined, and the bony bridges were scored on PD 4.5. In wild-type mice, tissue concentrations of meclozine in ED 17.5 fetuses and PD 6.5 pups were investigated.<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>RESULTS<\/jats:title>\n<jats:p>The area of the foramen magnum was significantly smaller in 17-day-old <jats:italic>Fgfr3<\/jats:italic><jats:sup>ach<\/jats:sup> mice than in wild-type mice (p &lt; 0.005). There were no bony bridges in the spheno-occipital and anterior intraoccipital synchondroses in wild-type mice, while some of the synchondroses prematurely closed in untreated <jats:italic>Fgfr3<\/jats:italic><jats:sup>ach<\/jats:sup> mice at PD 4.5. The average bony bridge score in the cranial base was 7.053 \u00b1 1.393 in untreated <jats:italic>Fgfr3<\/jats:italic><jats:sup>ach<\/jats:sup> mice and 6.125 \u00b1 2.029 in meclozine-treated <jats:italic>Fgfr3<\/jats:italic><jats:sup>ach<\/jats:sup> mice. The scores were not statistically significant between mice with and those without meclozine treatment (p = 0.12). The average tissue concentration of meclozine was significantly higher (508.88 \u00b1 205.16 ng\/g) in PD 6.5 mice than in ED 17.5 mice (56.91 \u00b1 20.05 ng\/g) (p &lt; 0.005).<\/jats:p><\/jats:sec>\n<jats:sec>\n<jats:title>CONCLUSIONS<\/jats:title>\n<jats:p>Maternal administration of meclozine postponed premature closure of synchondroses in some <jats:italic>Fgfr3<\/jats:italic><jats:sup>ach<\/jats:sup> mice, but the effect on preventing bony bridge formation was not significant, probably due to low placental transmission of the drug. Meclozine is likely to exhibit a marginal effect on premature closure of synchondroses at the cranial base in ACH.<\/jats:p><\/jats:sec>","DOI":"10.3171\/2016.7.peds16199","type":"journal-article","created":{"date-parts":[[2016,10,21]],"date-time":"2016-10-21T14:15:12Z","timestamp":1477059312000},"page":"91-95","source":"Crossref","is-referenced-by-count":9,"title":["Maternal administration of meclozine for the treatment of foramen magnum stenosis in transgenic mice with achondroplasia"],"prefix":"10.3171","volume":"19","author":[{"given":"Masaki","family":"Matsushita","sequence":"first","affiliation":[{"name":"Division of Neurogenetics, Center for Neurological Diseases and Cancer, and"},{"name":"Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Mishima","sequence":"additional","affiliation":[{"name":"Division of Neurogenetics, Center for Neurological Diseases and Cancer, and"},{"name":"Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryusaku","family":"Esaki","sequence":"additional","affiliation":[{"name":"Division of Neurogenetics, Center for Neurological Diseases and Cancer, and"},{"name":"Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Ishiguro","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinji","family":"Ohno","sequence":"additional","affiliation":[{"name":"Division of Neurogenetics, Center for Neurological Diseases and Cancer, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kitoh","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1-peds16199","series-title":"Am J Med Genet","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1002\/ajmg.1320320421","article-title":"Growth of the foramen magnum in achondroplasia","volume":"32","author":"Hecht JT,","year":"1989","unstructured":"Hecht JT, Horton WA, Reid CS, Pyeritz RE, Chakraborty R: Growth of the foramen magnum in achondroplasia. 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