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.
Zusammenfassung
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.
Warum dies für die Hirudotherapie relevant ist
This study examined whether hirudin — a salivary secretion of Hirudo medicinalis — protects against acute ischemic stroke by inhibiting NLRP3 inflammasome-mediated neuroinflammation, using a mouse middle cerebral artery occlusion/reperfusion model and an in vitro oxygen-glucose deprivation/reperfusion model in BV-2 microglia. Hirudin (10–40 mg/kg) dose-dependently reduced cerebral infarct area, improved locomotor function at 40 mg/kg, suppressed M1 microglial polarization while promoting M2 polarization, and reduced NLRP3, caspase-1, ASC, and IL-1β expression — effects comparable to the selective NLRP3 inhibitor MCC950. For ASH's domain, this directly extends the known pharmacology of a flagship leech-derived anticoagulant into neuroprotective and anti-inflammatory mechanisms, supporting broader therapeutic potential of the leech secretome. The caveat is that this is a preclinical animal and cell-culture study at pharmacological doses; it provides no human data, and the hirudin used appears to be a purified or recombinant preparation rather than whole leech therapy.
Zitation
Hirudin alleviates acute ischemic stroke by inhibiting NLRP3 inflammasome-mediated neuroinflammation.
Li WQ et al. · International immunopharmacology, 2022
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