Embolic Stroke Model with Magnetic Nanoparticles

ACS Appl Mater Interfaces. 2021 Sep 22;13(37):43993-44001. doi: 10.1021/acsami.1c11377. Epub 2021 Sep 8.

Abstract

Stroke models are vital tools in neuropharmacology and rehabilitation research. However, a classic and widely used model-the suture occlusion model-is not suitable for all research approaches, especially regarding thrombolysis. For embolic stroke models in thrombolytic research, the surgical procedures of thrombin injection in the middle cerebral artery or clot injection in the carotid artery involved are too sophisticated. Here, we report a new stroke model in mice that uses magnetic nanoparticle (MNP) cross-linked with thrombin to embolize. Briefly, after the magnet was positioned in the common carotid artery, MNP@Thrombin was injected from the tail vein. Within several minutes postinjection, the MNP@Thrombin accumulated in the carotid artery and induced thrombus formation. These complex clots were flushed into and subsequently blocked the cerebral artery. Collectively, these results suggested that this new method was a quick and easy stroke model that blocked hemisphere blood flow and damaged neural function. Importantly, this model had an excellent response to thrombolytic drugs. After urokinase injection, cerebral blood flow was restored and symptom scores were enhanced by nearly one. This method, including a quick synthesis of MNP and thrombin, provided an easy and minimally invasive process for a new stroke model that is usable in both pharmacological and rehabilitative research.

Keywords: embolize; magnetic nanoparticles; stroke; thrombin; thrombolysis.

MeSH terms

  • Animals
  • Carotid Arteries / metabolism
  • Cell Line
  • Cerebral Arteries / drug effects
  • Disease Models, Animal*
  • Embolic Stroke / chemically induced*
  • Embolic Stroke / drug therapy
  • Fibrinolytic Agents / metabolism
  • Fibrinolytic Agents / therapeutic use
  • Infarction, Middle Cerebral Artery / chemically induced*
  • Infarction, Middle Cerebral Artery / drug therapy
  • Magnetic Phenomena
  • Magnetite Nanoparticles / chemistry*
  • Mice
  • Mice, Inbred ICR
  • Thrombin / chemistry*
  • Thrombin / metabolism
  • Thrombolytic Therapy
  • Urokinase-Type Plasminogen Activator / metabolism
  • Urokinase-Type Plasminogen Activator / therapeutic use

Substances

  • Fibrinolytic Agents
  • Magnetite Nanoparticles
  • Thrombin
  • Urokinase-Type Plasminogen Activator