{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T19:52:43Z","timestamp":1776628363797,"version":"3.51.2"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,1,6]],"date-time":"2019-01-06T00:00:00Z","timestamp":1546732800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Hypoxic\u2010ischemic brain damage (HIBD), frequently occurring in infancy and childhood, is a major cause of mortality and severe neurologic impairment. This study was performed to examine the effect of the PI3K\/Akt signaling pathway on HIBD in a neonatal rabbit model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Uterine artery occlusion was used to establish HIBD models in neonatal rabbits, which were then subjected to sham operation, dimethyl sulfoxide (2\u2009mL) or LY294002 (inhibitor of PI3K\/Akt signaling pathway, 6.4\u2009\u03bcg\/kg). Behavioral neurological assessment was performed in neonatal rabbits delivered by cesarean section, after which serum neuron\u2010specific enolase (NSE) level and cerebral water content were determined. The level of cleaved caspase\u20103 level and apoptosis of neurons were observed by immunohistochemistry and terminal deoxynucleotidyl transferase\u2010mediated dUTP nick\u2010end labeling (TUNEL) staining. Furthermore, the expression of PI3K\/Akt signaling pathway\u2010 and apoptosis\u2010related factors was examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In neonatal rabbits, HIBD increased the fetal death rate; reduced neurological scores of posture, righting reflex, and deglutition reflex; elevated serum NSE levels, cerebral water content, cleaved caspase\u20103\u2010positive expression in hippocampal CA1 region and apoptotic neurons; inactivated PI3K\/Akt signaling pathway as well as reduced Bcl\u20102 expression and increased BAD and Bax expression. Notably, the treatment of LY294002 further aggravated neurological impairment in neonatal rabbits in response to HIBD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Following the HIBD caused by intrauterine asphyxia, the LY294002 administered through auricular vein infusion into pregnant rabbits exacerbates neurological impairment of neonatal rabbits, suggesting that inhibition of PI3K\/Akt signaling pathway may serve as a candidate therapeutic target for neurological recovery.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcb.28302","type":"journal-article","created":{"date-parts":[[2019,1,7]],"date-time":"2019-01-07T10:46:41Z","timestamp":1546858001000},"page":"10175-10185","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Inhibition of the PI3K\/Akt signaling pathway impedes the restoration of neurological function following hypoxic\u2010ischemic brain damage in a neonatal rabbit 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