Deep cortical microinfarction induced by femtosecond laser in mice: Long-term secondary pathological changes in corresponding superficial cortex

Abstract

Background and purpose: Previous studies have explored the clinical consequences of cortical microinfarction, mainly age-related cognitive decline. However, functional impairment of deep cortical microinfarction remains poorly understood. Based on anatomical knowledge and previous research, we infer that damage to the deep cortex may lead to cognitive deficits and communication impairment between the superficial cortex and thalamus. This study aimed to develop a new model of deep cortical microinfarction based on femtosecond laser ablation of a perforating artery.

Methods: Twenty-eight mice were anesthetized with isoflurane, and a cranial window was thinned using a microdrill. Intensively focused femtosecond laser pulses were used to produce perforating arteriolar occlusions and ischemic brain damage was examined using histological analysis.

Results: Occlusion of different perforating arteries induced different types of cortical microinfarctions. Blocking the perforating artery, which enters the cerebral cortex vertically and has no branches within 300 μm below, can result in deep cortical microinfarction. Moreover, this model showed neuronal loss and microglial activation in the lesions as well as dysplasia of nerve fibers and β-amyloid deposition in the corresponding superficial cortex.

Conclusions: We present here a new model of deep cortical microinfarction in mice, in which specific perforating arteries are selectively occluded by a femtosecond laser, and we preliminarily observe several long-term effects related to cognition. This animal model is helpful in investigating the pathophysiology of deep cerebral microinfarction. However, further clinical and experimental studies are required to explore deep cortical microinfarctions in greater molecular and physiological detail.

Keywords: Cortex; Ischemia; Mice; Stroke; Two-photon microscopy.