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The occurrence of depression is often associated with frontal lobe hemorrhage, however, current understanding of the underlying mechanisms remains limited. Here, the pathogenic mechanisms associated with the circuitry connectivity, electrophysiological alterations, and molecular characteristics are investigated related to the frontal lobe in adult male mice following unilateral injection of blood in the medial prefrontal cortex (mPFC). It is demonstrated that depression is a specific neurological complication in the unilateral hematoma model of the mPFC, and the ventral tegmental area (VTA) shows a higher percentage of connectivity disruption compared to the lateral habenula (LHb) and striatum (STR). Additionally, long\u2010range projections originating from the frontal lobe demonstrate higher damage percentages within the connections between each region and the mPFC. mPFC neurons reveal reduced neuronal excitability and altered synaptic communication. Furthermore, transcriptomic analysis identifies the involvement of the Janus Kinase\u2010Signal Transducer and Activator of Transcription (JAK\u2010STAT)\u00a0signaling pathway, and targeting the JAK\u2010STAT pathway significantly alleviates the severity of depressive symptoms. These findings improve the understanding of post\u2010hemorrhagic depression and may guide the development of efficient treatments.<\/jats:p>","DOI":"10.1002\/advs.202402152","type":"journal-article","created":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T04:59:13Z","timestamp":1719809953000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Unraveling the Pathogenesis of Post\u2010Stroke Depression in a Hemorrhagic Mouse Model through Frontal Lobe Circuitry and JAK\u2010STAT Signaling"],"prefix":"10.1002","volume":"11","author":[{"given":"Yingqing","family":"Wu","sequence":"first","affiliation":[{"name":"Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering Chongqing University  Chongqing 400030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Deng","sequence":"additional","affiliation":[{"name":"College of Environment and Resources Chongqing Technology and Business University  Chongqing 400030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinsong","family":"Ma","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering Chongqing University  Chongqing 400030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery and State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital Third Military Medical University (Army Medical University)  Chongqing 400038 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering Chongqing University  Chongqing 400030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1205-3102","authenticated-orcid":false,"given":"Shilei","family":"Hao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering Chongqing University  Chongqing 400030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bochu","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering Chongqing University  Chongqing 400030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.166.3.328"},{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(11)70264-2"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.122.040331"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.3142"},{"key":"e_1_2_10_3_3","doi-asserted-by":"publisher","DOI":"10.3233\/NRE-171470"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcn.13633"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2023.10.037"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2023.12.012"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.918531"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2022.853804"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00406-017-0794-x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X221135419"},{"key":"e_1_2_10_9_2","author":"Wu Y.","year":"2024","journal-title":"Transl. 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