Nephrogenic systemic fibrosis (NSF) is a rare and a debilitating disease noted uncommonly in patients with impaired renal function when exposed to low-stability gadolinium-based contrast agents (Gd-CAs). According to experimental studies, cytokines released by the stimulation of effector cells such as skin macrophages and peripheral blood monocytes activate circulating fibroblasts which play a major role in the development of NSF lesions. The presence of permissive factors, presumably, provides an environment conducive to facilitate the process of fibrosis. Multiple treatment modalities have been tried with variable success rates. More research is necessary to elucidate the underlying pathophysiological mechanisms which could potentially target the initial steps of fibrosis in these patients. This paper attempts to collate the inferences from the in vivo and in vitro experiments to the clinical observations to understand the pathogenesis of NSF. Schematic representations of receptor-mediated molecular pathways of activation of macrophages and fibroblasts by gadolinium and the final pathway to fibrosis are incorporated in the discussion.

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Emerging literature has highlighted the relationship between inflammatory and neuroinflammatory biomarkers and tinnitus. Neuroinflammation may help to explain the mechanisms underpinning hyperactivity in the cochlea, cochlear nucleus, inferior colliculus, medial geniculate body, and the auditory cortex in those with tinnitus. Glial activation and pro-inflammatory cytokines may cause excitatory-inhibitory synaptic imbalance. Advancing our understanding of these mechanisms may help elucidate the pathogenesis of tinnitus and lead to improvement in subtyping subjective tinnitus. The chapter explores our current understanding of the neuroinflammatory model within the context of the classical auditory pathway and what we can infer about the underlying mechanisms based on these studies.