{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T21:06:33Z","timestamp":1769115993821,"version":"3.49.0"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,8,28]],"date-time":"2016-08-28T00:00:00Z","timestamp":1472342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Encephalopathy of prematurity (EOP) is a complex form of cerebral injury that occurs in the setting of hypoxia\u2010ischemia (HI) in premature infants. Using a rat model of EOP, we investigated whether neonatal HI of the brain may alter the expression of cystathionine \u03b2\u2010synthase (CBS) and the components of the mammalian target of rapamycin (mTOR) signaling. We performed unilateral carotid ligation and induced HI (UCL\/HI) in Long\u2010Evans rats at P6 and found increased CBS expression in white matter (i.e. corpus callosum, cingulum bundle and external capsule) as early as 24 h (P7) postprocedure. CBS remained elevated through P21, and, to a lesser extent, at P40. The mTOR downstream target 70 kDa ribosomal protein S6 kinase (p70S6K and phospho\u2010p70S6K) and 40S ribosomal protein S6 (S6 and phospho\u2010S6) were also overexpressed at the same time points in the UCL\/HI rats compared to healthy controls. Overexpression of mTOR components was not observed in rats treated with the mTOR inhibitor everolimus. Behavioral assays performed on young rats (postnatal day 35\u201337) following UCL\/HI at P6 indicated impaired preference for social novelty, a behavior relevant to autism spectrum disorder, and hyperactivity. Everolimus restored behavioral patterns to those observed in healthy controls. A gait analysis has shown that motor deficits in the hind paws of UCL\/HI rats were also significantly reduced by everolimus. Our results suggest that neonatal HI brain injury may inflict long\u2010term damage by upregulation of CBS and mTOR signaling. We propose this cascade as a possible new molecular target for EOP\u2014a still untreatable cause of autism, hyperactivity and cerebral palsy.<\/jats:p>","DOI":"10.1111\/bpa.12421","type":"journal-article","created":{"date-parts":[[2016,7,28]],"date-time":"2016-07-28T08:27:10Z","timestamp":1469694430000},"page":"449-458","source":"Crossref","is-referenced-by-count":16,"title":["Upregulation of cystathione \u03b2\u2010synthase and p70S6K\/S6 in neonatal hypoxic ischemic brain injury"],"prefix":"10.1111","volume":"27","author":[{"given":"Mirna","family":"Lechpammer","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of California Davis Sacramento CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yen P.","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of California Davis Sacramento 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