Hirudin alleviates acute ischemic stroke by inhibiting NLRP3 inflammasome-mediated neuroinflammation
Basic science / preclinical published in Int Immunopharmacol (2022)
Abstract
Acute ischemic stroke is a severe condition that a vessel supplying blood to the brain is abruptly blocked mostly due to cerebral thrombosis and embolism. There is a dearth of the effective prevention and early intervention strategies. NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation plays a crucial role in the pathophysiology of ischemic stroke. Hirudin is a secretion from the salivary glands of the leech Hirudo medicinalis and has a role in regulating inflammation. In this study, hirudin with a dose of 10-40 mg/kg was given to middle cerebral artery occlusion/reperfusion mice. Hirudin markedly constrained cerebral infarct area in a dose-dependent manner, and significantly improved locomotor disability at 40 mg/kg dose. Similar to MCC950, a selective NLRP3 inflammasome inhibitor, hirudin inhibited M1 polarization and promoted M2 polarization. It also strikingly suppressed the ischemia-induced overexpression of NLRP3 and its downstream components, caspase-1, apoptosis-associated speck-like protein (ASC), and interleukin-1β (IL-1β). Hirudin and MCC950 equivalently protected viability and death of BV-2 microglia cells against oxygen-glucose deprivation/reperfusion (OGD/R), an in vitro cell model of brain ischemia. Both agents had similar effects in normalizing the OGD/R-evoked aberrant microglial profiles and NLRP3 pathway dysregulation as observed in the mice. These results demonstrated anti-ischemic effects of hirudin and its association with the inhibition of microglial NLRP3 inflammasome-mediated neuroinflammation. Hirudin is a promising agent for the early intervention of acute ischemic stroke.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Hirudin (10-40 mg/kg) reduces cerebral infarct size, suppresses NLRP3 inflammasome activation, modulates microglial M1/M2 polarization, and downregulates caspase-1/ASC/IL-1beta in MCAO/R mice and OGD/R BV-2 microglial models.
Por qué esto importa para la hirudoterapia
Este estudio examinó si la hirudina —una secreción salival de Hirudo medicinalis— protege contra el accidente cerebrovascular isquémico agudo mediante la inhibición de la neuroinflamación mediada por el inflamasoma NLRP3, utilizando un modelo de oclusión de la arteria cerebral media seguida de reperfusión en ratón y un modelo in vitro de privación de oxígeno-glucosa seguida de reperfusión en microglía BV-2. La hirudina (10–40 mg/kg) redujo de forma dosis-dependiente el área de infarto cerebral, mejoró la función locomotora a 40 mg/kg, suprimió la polarización microglial M1 mientras promovió la polarización M2, y redujo la expresión de NLRP3, caspasa-1, ASC e IL-1β —efectos comparables al inhibidor selectivo de NLRP3 MCC950. Para el dominio de la ASH, esto amplía directamente la farmacología conocida de un anticoagulante emblemático derivado de sanguijuela hacia mecanismos neuroprotectores y antiinflamatorios, lo que respalda un potencial terapéutico más amplio del secretoma de la sanguijuela. La advertencia es que se trata de un estudio preclínico en animales y en cultivo celular a dosis farmacológicas; no aporta datos en humanos, y la hirudina utilizada parece ser una preparación purificada o recombinante en lugar de terapia con sanguijuela completa.
Citación
Hirudin alleviates acute ischemic stroke by inhibiting NLRP3 inflammasome-mediated neuroinflammation.
Li WQ et al. · International immunopharmacology, 2022
Contexto clínico relacionado
Explore cómo esta investigación se conecta con la práctica clínica
Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026