Development of a rat model of photothrombotic ischemia and infarction within the caudoputamen.

ABSTRACT

BACKGROUND AND PURPOSE: Basal ganglia infarction is typically caused by the occlusion of deep arteries and the formation of relatively small lesions called lacunes. In the present study, a rat model of lacunar infarction was induced by photothrombotic occlusion of the small vessels within the caudate-putamen and subsequently characterized. METHODS: Male Sprague-Dawley rats (n=143) were anesthetized, and Rose Bengal dye (20 mg/kg) was intravenously injected. The left caudoputamen was exposed to cold white light for 5 to 10 minutes via a stereotaxically implanted polymethylmethacrylate optic fiber (0.5-0.75 mm diameter). Neurological and morphological changes were assessed at various times during the following 6 weeks. Local cerebral blood flow was measured 90 minutes after photothrombosis by [(14)C]-N-isopropyl-p-iodoamphetamine quantitative autoradiography. The time course of blood-brain barrier opening and ischemic brain edema as well as the effects of aspirin and tissue plasminogen activator treatment were also determined. RESULTS: A virtually round infarct with thrombosed parenchymal vessels surrounded by a layer of selective neuronal death was formed within the caudoputamen; it turned into a cystic cavity (lacune) over 6 weeks. A central zone of markedly reduced blood flow and surrounding oligemic zone were observed 90 minutes after light exposure. Lesion size was proportional to light exposure, and the severity and duration of neurological deficits paralleled infarct size. Early blood-brain barrier opening with edema peaked at day 1. After tissue plasminogen activator treatment, infarction volume and neurological deficits were reduced. CONCLUSIONS: This study describes a new rat model of lacunar infarction by photothrombotic occlusion of the microvessels within the caudoputamen. With this model, infarct size correlates with the severity and duration of the neuropathology and can be varied by altering light exposure.