Borjini Nozha, Fernandez Mercedes, Giardino Luciana, Sorokin Lydia, Calzà Laura
Research & Development, Chiesi Farmaceutici S.p.A, via Palermo 26/A, 43100 Parma, Italy.
IRET Foundation, via Tolara di Sopra 41/E, Ozzano Emilia, 40064 Bologna, Italy.
Cells. 2025 Mar 12;14(6):414. doi: 10.3390/cells14060414.
Blood-brain barrier dysfunction (BBB) is a primary characteristic of experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS). We have previously shown that blocking microglial proliferation using GW2580, a selective inhibitor of CSF1R (Colony stimulating factor 1 receptor), reduced disease progression and severity and prevented the relapse phase. However, whether this was due to effects of GW2580 on the functional integrity of the BBB was not determined. Therefore, here, we examine BBB properties in rats during EAE under GW2580 treatment. Our data suggest that blocking early microglial proliferation through selective targeting of CSF1R signaling has a therapeutic effect in EAE by protecting BBB integrity and reducing peripheral immune cell infiltration. Taken together, our results identify a novel mechanism underlying the effects of GW2580, which could offer a novel therapy for MS.
血脑屏障功能障碍（BBB）是实验性自身免疫性脑脊髓炎（EAE）的主要特征，EAE是多发性硬化症（MS）的一种实验模型。我们之前已经表明，使用CSF1R（集落刺激因子1受体）的选择性抑制剂GW2580阻断小胶质细胞增殖，可降低疾病进展和严重程度，并预防复发阶段。然而，这是否归因于GW2580对血脑屏障功能完整性的影响尚未确定。因此，在此我们研究了GW2580治疗的EAE大鼠的血脑屏障特性。我们的数据表明，通过选择性靶向CSF1R信号传导阻断早期小胶质细胞增殖，可通过保护血脑屏障完整性和减少外周免疫细胞浸润，对EAE产生治疗作用。综上所述，我们的结果确定了GW2580作用的一种新机制，这可能为MS提供一种新的治疗方法。
