The use of manganese-enhanced MRI for the evaluation of neurodegenerative changes in a rat model of kainic acid- induced excitotoxicity

Abstract

Manganese-enhanced magnetic resonance imaging (MEMRI) has been used to detect brain activity based on the ability of active neurons to take up manganese ions through calcium channels. Kainic acid (KA), an analog of excitotoxic glutamate, can elicit selective neuronal death in the brains of rodents, of which the pathological changes partially mimic neurodegeneration in the central nervous system. We used in vivo MEMRI to evaluate neurodegenerative changes in an excitotoxicity model induced by KA in rats. Adult Sprague-Dawley rats (220-250 g) were injected with either KA or saline into the right lateral ventricle. Precontrast and postcontrast MEMRI sessions were obtained. Region of interest (ROI) analyses were performed on both injected (saline and KA) and contralateral (normal) sites in the hippocampal area. All brains were evaluated histologically following MEMRI. Analysis of percentage change in ROI intensities of T1-weighted fluid-attenuated inversion-recovery MR images in the hippocampal area revealed a significant difference between the KA-injected (ipsilateral) and contralateral sites (P = 0.008), whereas no significant difference was observed between the saline-injected and contralateral sites. Furthermore, there was a significant difference between ipsilateral sites of the saline-treated and KA-treated groups (P = 0.026). The histological results supported these findings. MEMRI is a simple and useful in vivo method for detecting neurodegenerative changes due to excitotoxicity in the rat brain. The development of a manganese-based contrast agent that can be safely used in humans is warranted to investigate neurological disorders.