{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T16:16:14Z","timestamp":1781712974381,"version":"3.54.5"},"reference-count":52,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,6,11]],"date-time":"2020-06-11T00:00:00Z","timestamp":1591833600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Science Foundation of China","award":["81260178"],"award-info":[{"award-number":["81260178"]}]},{"name":"the National Science Foundation of China","award":["81560215"],"award-info":[{"award-number":["81560215"]}]},{"name":"Technology Innovation Team for Prevention and Treatment of Encephalopathy by the Integrated Chinese and Western Medicine in Luzhou City","award":["2018229"],"award-info":[{"award-number":["2018229"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Neonatal hypoxia\u2013ischemic brain damage (HIBD) can lead to serious neuron damage and dysfunction, causing a significant worldwide health problem. bFGF as a protective reagent promotes neuron repair under hypoxia\/ischemia (HI). However, how bFGF and downstream molecules were regulated in HI remains elusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We established an in vitro HI model by culturing primary cortical neurons and treated with oxygen\u2013glucose deprivation (OGD). We suppressed the expression of bFGF by using siRNA (small interfering RNA) interference to detect the neuronal morphological changes by immunofluorescence staining. To determine the potential mechanisms regulated by bFGF, the change of downstream molecular including IL\u20101\u03b2 was examined in bFGF knockdown condition. IL\u20101\u03b2 knockout (KO) rats were generated using CRISPR\/Cas9\u2010mediated technologies. We used an accepted rat model of HI, to assess the effect of IL\u20101\u03b2 deletion on disease outcomes and carried out analysis on the behavior, histological, cellular, and molecular level.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified that OGD can induce endogenous expression of bFGF. Both OGD and knockdown of bFGF resulted in reduction of neuron numbers, enlarged cell body and shortened axon length. We found molecules closely related to bFGF, such as interleukin\u20101\u03b2 (IL\u20101\u03b2). IL\u20101\u03b2 was up\u2010regulated after bFGF interference under OGD conditions, suggesting complex signaling between bFGF and OGD\u2010mediated pathways. We found HI resulted in up\u2010regulation of IL\u20101\u03b2 mRNA in cortex and hippocampus. IL\u20101\u03b2 KO rats markedly attenuated the impairment of long\u2010term learning and memory induced by HI. Meanwhile, IL\u20101\u03b2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      (KO, homozygous) group showed better neurite growth and less apoptosis in OGD model. Furthermore, serine\/threonine protein kinase (AKT1) mRNA and protein expression was significantly up\u2010regulated in IL\u20101\u03b2 KO rats.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We showed that IL\u20101\u03b2\u2010mediated axon regeneration underlie the mechanism of bFGF for the treatment of HIBD in neonatal rats. Results from this study would provide insights and molecular basis for future therapeutics in treating HIBD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.1696","type":"journal-article","created":{"date-parts":[[2020,6,11]],"date-time":"2020-06-11T05:44:06Z","timestamp":1591854246000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["bFGF promotes neurological recovery from neonatal hypoxic\u2013ischemic encephalopathy by IL\u20101\u03b2 signaling pathway\u2010mediated axon regeneration"],"prefix":"10.1002","volume":"10","author":[{"given":"Zheng","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Anatomy Kunming Medical University Kunming China"},{"name":"Qingdao Huanghai University Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience Laboratory Zoology Department Kunming Medical University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu\u2010Lu","family":"Xue","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience Laboratory Zoology Department Kunming Medical University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying\u2010Jie","family":"Niu","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience Laboratory Zoology Department Kunming Medical University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Hu","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience Laboratory Zoology Department Kunming Medical University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhang\u2010Yu","family":"Su","sequence":"additional","affiliation":[{"name":"National Traditional Chinese Medicine Clinical Research Base and Western Medicine Translational Medicine Research Center Affiliated Traditional Chinese Medicine Hospital Southwest Medical University Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience Laboratory Zoology Department Kunming Medical University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui\u2010Ze","family":"Niu","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience Laboratory Zoology Department Kunming Medical University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting\u2010Hua","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience Laboratory Zoology Department Kunming Medical University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying\u2010Chun","family":"Ba","sequence":"additional","affiliation":[{"name":"Department of Anatomy Kunming Medical University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1623-5969","authenticated-orcid":false,"given":"Liu\u2010Lin","family":"Xiong","sequence":"additional","affiliation":[{"name":"National Traditional Chinese Medicine Clinical Research Base and Western Medicine Translational Medicine Research Center Affiliated Traditional Chinese Medicine Hospital Southwest Medical University Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Bai","sequence":"additional","affiliation":[{"name":"National Traditional Chinese Medicine Clinical Research Base and Western Medicine Translational Medicine Research Center Affiliated Traditional Chinese Medicine Hospital Southwest Medical University Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2005.06.006"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2015.87"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(89)90057-8"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199606170-00003"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2019.05.010"},{"key":"e_1_2_11_7_1","first-page":"299","article-title":"Activating Akt and the brain's resources to drive cellular survival and prevent inflammatory injury","volume":"20","author":"Chong Z. 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