A Practical Method for Creating Targeted Focal Ischemic Stroke in the Cortex of Nonhuman Primates*

摘要

Ischemic stroke is a major cause of disability among adults worldwide. Despite its prevalence, few effective treatment options exist to alleviate sensory and motor dysfunctions that result from stroke. In the past, rodent models of stroke have been the primary experimental models used to develop stroke therapies. However, positive results in these studies have failed to replicate in human clinical trials, highlighting the importance of nonhuman primate (NHP) models as a preclinical step. Although there are a few NHP models of stroke, the extent of tissue damage is highly variable and dependent on surgical skill. In this study, we employed the photothrombotic stroke model in NHPs to generate controlled, reproducible ischemic lesions. Originally developed in rodents, the photothrombotic technique consists of intravenous injection of a photosensitive dye such as Rose Bengal followed by illumination of an area of interest to induce endothelial damage resulting in the formation of thrombi in the illuminated vasculature. We developed a quantitative model to predict the extent of tissue damage based on the light scattering profile of light in the cortex of NHPs. We then employed this technique in the sensorimotor cortex of two adult male Rhesus Macaques. In vivo optical coherence tomography imaging of the cortical microvasculature and subsequent histology confirmed the formation of focal cortical infarcts and demonstrated its reproducibility and ability to control the sizes and locations of light-induced ischemic lesions in the cortex of NHPs. This model has the potential to enhance our understanding of perilesional neural dynamics and can be used to develop reliable neurorehabilitative therapeutic strategies to treat stroke.