大腦多巴胺生長因子可藉由調節免疫細胞的功能加速血塊清除並促進腦出血後神經功能的恢復

Augmenting Hematoma-Scavenging Capacity of Innate Immune Cells by CDNF Reduces Brain Injury and Promotes Functional Recovery after Intracerebral Hemorrhage

10.6318/FJS.202409_6(3).0005

曾冠穎(Tseng Kuan-Yin)；胡瑋芬(Wei-Fen Hu)；吳瑞昇(Jui-Sheng Wu)；王菁(Vicki Wang)；陳元皓(Yuan-Hao Chen)；廖學健(Hock-Kean Liew)

Intracerebral hemorrhage ； Cerebral dopamine neurotrophic factor (CDNF) ； neuroinflammation ； Disease-associated microglia ； hematoma-scavenging microglia

台灣中風醫誌

6卷3期（2024 / 09 / 01）

246 - 251

繁體中文;英文

During intracerebral hemorrhage (ICH), hematoma formation at the site of blood vessel damage results in local mechanical injury. Subsequently, erythrocytes lyse to release hemoglobin and heme, which act as neurotoxins and induce inflammation and secondary brain injury, resulting in severe neurological deficits. Accelerating hematoma resorption and mitigating hematoma-induced brain edema by modulating immune cells has potential as a novel therapeutic strategy for functional recovery after ICH. Here, we show that intracerebroventricular administration of recombinant human cerebral dopamine neurotrophic factor (rhCDNF) accelerates hemorrhagic lesion resolution, reduces peri-focal edema, and improves neurological outcomes in an animal model of collagenase-induced ICH. We demonstrate that CDNF acts on microglia/ macrophages in the hemorrhagic striatum by promoting scavenger receptor expression, enhancing erythrophagocytosis and increasing anti-inflammatory mediators while suppressing the production of pro-inflammatory cytokines. Administration of rhCDNF results in upregulation of the Nrf2-HO-1 pathway, but alleviation of oxidative stress and unfolded protein responses in the perihematomal area. Finally, we demonstrate that intravenous delivery of rhCDNF has beneficial effects in an animal model of ICH and that systemic application promotes scavenging by the brain's myeloid cells for the treatment of ICH.