Transient ischemic attack induced by melted solid lipid microparticles protects rat brains from permanent focal ischemia

- Injection of temperature-melted lipid particles induces transient ischemic attack.
- Neurologic deficit is monitored in conscious rats.
- Injection of blending chitin/PLGA particles induces permanent ischemia.
- Transient ischemia (<24 h) preconditioning protects rats following ischemic attack.

This study aims to develop a transient ischemic attack (TIA) model in conscious animals and uses this model to investigate the effect of TIA on subsequent permanent ischemia. TIA was induced by injecting designed temperature-sensitive melted solid lipid microparticles with a melting point around body temperature into male Wistar rats via arterial cannulation. Neurologic deficit was monitored immediately after the injection without anesthesia. According to the clinical definition of TIA, rats were divided into neurologic symptom durations <24-h, 24-48-h and ⩾48-h groups. The lipid microparticle-induced infarct volumes were small in the <24-h and 24-48-h groups, while the volumes were five times larger in the ⩾48-h group. Permanent ischemic stroke was induced 3 d after the induction of TIA by injecting a different kind of embolic particle manufactured by blending chitin and PLGA. The <24-h group had less severe neurologic deficits and smaller infarct volumes than that of 24-48-h and control (without prior lipid microparticle treatment) rats. Taken together, we successfully develop a TIA animal model which allows us to monitor the neurologic deficit in real-time. By adopting this model, we validate that TIA (<24 h) preconditioning protects the brain from subsequent permanent ischemic stroke.