Hirudin promotes cerebral angiogenesis and exerts neuroprotective effects in MCAO/R rats by activating the Wnt/-catenin pathway
Research article published in J Stroke Cerebrovasc Dis (2025)
Abstract
OBJECTIVE: Hirudin has shown potential in promoting angiogenesis and providing neuroprotection in ischemic stroke; however, its therapeutic role in promoting cerebrovascular angiogenesis remains unclear. In this study, we aimed to investigate whether hirudin exerts neuroprotective effects by promoting angiogenesis through the regulation of the Wnt/β-catenin signaling pathway. METHODS: An in vitro model of glucose and oxygen deprivation/reperfusion (OGD/R) was established using rat brain microvascular endothelial cells (BMECs). The effects of hirudin on OGD/R cell viability were assessed using the cell counting kit-8 (CCK-8) assay. The angiogenic potential of hirudin was evaluated using Transwell and tube formation assays. In vivo, a middle cerebral artery occlusion/reperfusion (MCAO/R) model was created in rats. The neuroprotective effects of hirudin were assessed using the modified neurological severity score (mNSS), Hematoxylin and eosin (H&E) staining, 2,3,5-Triphenyltetrazolium chloride (TTC) staining, and immunofluorescence staining. Dickkopf-1 (DKK1), a specific inhibitor of this pathway, was introduced in order to investigate the role of the Wnt/β-catenin pathway. The effects of hirudin on the Wnt/β-catenin pathway were examined through immunohistochemistry, western blotting, and reverse transcription quantitative polymerase chain reaction (RT-qPCR). RESULTS: Hirudin significantly improved BMEC survival and enhanced both cell migration and tube formation in the OGD/R model. In the MCAO/R model, hirudin reduced the mNSS score, alleviated pathological damage, decreased infarction volume, and increased the expression of key angiogenic factors, including CD34, vascular endothelial growth factor (VEGF), and angiopoietin-2 (Ang-2). In addition, hirudin activated the Wnt/β-catenin pathway, leading to elevated levels of Wnt3a and β-catenin. CONCLUSION: Hirudin has substantial neuroprotective effects associated with the promotion of angiogenesis in the ischemic penumbra. This mechanism is mediated by the regulation of the Wnt/β-catenin pathway.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Hirudin has shown potential in promoting angiogenesis and providing neuroprotection in ischemic stroke; however, its therapeutic role in promoting cerebrovascular angiogenesis remains unclear.
Por qué esto importa para la hirudoterapia
Este estudio investigó si la hirudina ejerce efectos neuroprotectores mediante la promoción de la angiogénesis a través de la vía de señalización Wnt/β-catenina, empleando un modelo in vitro de privación de oxígeno y glucosa/reperfusión en células endoteliales microvasculares cerebrales de rata y un modelo in vivo de oclusión de la arteria cerebral media/reperfusión en rata. La hirudina mejoró la supervivencia, la migración y la formación de túbulos de las células endoteliales in vitro, y in vivo redujo las puntuaciones de gravedad neurológica, el volumen del infarto y el daño patológico, al tiempo que aumentó la expresión de factores angiogénicos (CD34, VEGF, Ang-2) y activó Wnt3a/β-catenina. Este estudio es relevante para el ámbito de ASH porque examina directamente la hirudina como agente terapéutico en el accidente cerebrovascular isquémico, aunque el resumen no indica su origen biológico ni su relación con la terapia con sanguijuelas. Advertencia: Se trata de un estudio preclínico en animales e in vitro, y los hallazgos no han sido validados en ensayos clínicos en humanos.
Citación
Hirudin promotes cerebral angiogenesis and exerts neuroprotective effects in MCAO/R rats by activating the Wnt/-catenin pathway.
He L et al. · J Stroke Cerebrovasc Dis, 2025
Contexto clínico relacionado
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026