Mapping acute neuroinflammation in vivo with diffusion-MRI in rats given a systemic lipopolysaccharide challenge.

It is becoming increasingly apparent that neuroinflammation plays a critical role in an array of neurological and psychiatric disorders. Recent studies have demonstrated the potential of diffusion MRI (dMRI) to characterize changes in microglial density and morphology associated with neuroinflammation, but these were conducted mostly ex vivo and/or in extreme, non-physiological animal models. Here, we build upon these studies by investigating the utility of well-established dMRI methods to detect neuroinflammation in vivo in a more clinically relevant animal model of sickness behavior. We show that diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) indicate widespread increases in diffusivity in the brains of rats given a systemic lipopolysaccharide challenge (n = 20) vs. vehicle-treated controls (n = 12). These diffusivity changes correlated with histologically measured changes in microglial morphology, confirming the sensitivity of dMRI to neuroinflammatory processes. This study marks a further step towards establishing a noninvasive indicator of neuroinflammation, which would greatly facilitate early diagnosis and treatment monitoring in various neurological and psychiatric diseases.

Nitroglycerin as a model of migraine: Clinical and preclinical review.

Migraine stands as one of the most disabling neurological conditions worldwide. It is a disorder of great challenge to study given its heterogeneous representation, cyclic nature, and complexity of neural networks involved. Despite this, clinical and preclinical research has greatly benefitted from the use of the nitric oxide donor, nitroglycerin (NTG), to model this disorder, dissect underlying mechanisms, and to facilitate the development and screening of effective therapeutics. NTG is capable of triggering a migraine attack, only in migraineurs or patients with a history of migraine and inducing migraine-like phenotypes in rodent models. It is however unclear to what extent NTG and NO, as its breakdown product, is a determinant factor in the underlying pathophysiology of migraine, and importantly, whether it really does facilitate the translation from the bench to the bedside, and vice-versa. This review provides an insight into the evidence supporting the strengths of this model, as well as its limitations, and shines a light into the possible role of NO-related mechanisms in altered molecular signalling pathways.