Hirudin alleviates acute ischemic stroke by inhibiting NLRP3 inflammasome-mediated neuroinflammation: In vivo and in vitro approaches
Animal model study published in International Immunopharmacology (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) dose-dependently reduced cerebral infarct area in middle cerebral artery occlusion mice via inhibition of NLRP3 inflammasome, M1 microglial polarization, and IL-1β release — extending hirudin's role beyond anticoagulation to neuroinflammation.
Por qué esto importa para la hirudoterapia
Este estudio investigó si la hirudina—una secreción de las glándulas salivales de la sanguijuela Hirudo medicinalis que desempeña un papel en la regulación de la inflamación—alivia el accidente cerebrovascular isquémico agudo mediante la inhibición de la neuroinflamación mediada por el inflamasoma NLRP3. Utilizando enfoques tanto in vivo (ratones con oclusión de la arteria cerebral media/reperfusión, 10–40 mg/kg) como in vitro (microglía BV-2 con privación de oxígeno-glucosa/reperfusión), la hirudina redujo de forma dosis-dependiente el área del infarto cerebral, mejoró la función locomotora a 40 mg/kg, suprimió la polarización microglial M1, promovió la polarización M2 y redujo la expresión de NLRP3, caspasa-1, ASC e IL-1β, con efectos comparables al inhibidor de NLRP3 MCC950. Esto es relevante para el ámbito de la ASH, ya que el resumen identifica la hirudina como una secreción salival de la sanguijuela y caracteriza un mecanismo antiinflamatorio en el accidente cerebrovascular. Sin embargo, se trata de hallazgos preclínicos obtenidos en modelos de ratón y cultivo celular; no se presentan datos clínicos ni humanos.
Citación
Hirudin alleviates acute ischemic stroke by inhibiting NLRP3 inflammasome-mediated neuroinflammation: In vivo and in vitro approaches.
Li WQ et al. · International Immunopharmacology, 2022
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026