{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T05:34:51Z","timestamp":1787722491352,"version":"build-2784847793"},"reference-count":40,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2007,5,1]],"date-time":"2007-05-01T00:00:00Z","timestamp":1177977600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2007,5]]},"abstract":"<jats:p>c-Jun N-terminal kinase 3 (JNK3) is a member of the stress-activated group of mitogen-activated protein kinases. c-Jun N-terminal kinase 3 is a potent mediator of apoptosis and the use of JNK inhibitors or jnk3 gene deletion each protect against brain injury in adults. However, little is known about the role of JNK3 or its mechanism of action in neonatal brain injury. The aim of the present study was to compare the vulnerability of neonatal JNK3 knockout (JNK3 KO) mice and wild-type (WT) mice to cerebral hypoxic\u2014ischaemic injury (HII) using unilateral-carotid occlusion combined with transient hypoxia. The degree of neural tissue loss in JNK3 KO mice was substantially reduced compared with WT mice (JNK3 KO 27.8% \u00b1 2.8% versus WT 48.3% \u00b1 2.0%, P \u2264 0.0001) after HII. Significant attenuation of injury was observed in the cerebral cortex, hippocampus, striatum, and thalamus of JNK3 KO compared with WT mice. Hypoxic\u2014ischaemic injury increased JNK phosphorylation and activity, with JNK3 as the major isoform. Significantly, in JNK3 KO animals there was no difference in the activation of the upstream kinases mitogen-activated protein kinase kinase (MKK4) or MKK7. Downstream of JNK3, HII lead to increased phosphorylation of the transcription factors c-Jun and adenovirus transcription factor-2 (ATF-2), which was attenuated in JNK3 KO mice. c-Jun N-terminal kinase 3 deletion also decrease caspase-3 cleavage and Bim\/PUMA expression, coupled with a upregulation of AKT\/FOXO3a levels, linking JNK3 to apoptosis. These findings implicate JNK3 involvement in neural cell loss resulting from cerebral HII in the developing brain.<\/jats:p>","DOI":"10.1038\/sj.jcbfm.9600413","type":"journal-article","created":{"date-parts":[[2006,10,25]],"date-time":"2006-10-25T04:40:26Z","timestamp":1161751226000},"page":"1022-1032","source":"Crossref","is-referenced-by-count":78,"title":["Deletion of the c-Jun N-terminal Kinase 3 Gene Protects Neonatal Mice against Cerebral Hypoxic\u2014Ischaemic Injury"],"prefix":"10.1177","volume":"27","author":[{"given":"Grisha","family":"Pirianov","sequence":"first","affiliation":[{"name":"Division of Clinical Sciences, Institute of Reproductive and Developmental Biology, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, UK"},{"name":"Clinical Sciences Division, Imperial College London, Hammersmith Hospital Campus, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina 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