Neuroscience
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Primary Neural Degeneration in the Human Cochlea: Evidence for Hidden Hearing Loss in the Aging Ear.
The noise-induced and age-related loss of synaptic connections between auditory-nerve fibers and cochlear hair cells is well-established from histopathology in several mammalian species; however, its prevalence in humans, as inferred from electrophysiological measures, remains controversial. Here we look for cochlear neuropathy in a temporal-bone study of "normal-aging" humans, using autopsy material from 20 subjects aged 0-89 yrs, with no history of otologic disease. Cochleas were immunostained to allow accurate quantification of surviving hair cells in the organ Corti and peripheral axons of auditory-nerve fibers. ⋯ The results suggest that a large number of auditory neurons in the aging ear are disconnected from their hair cell targets. This primary neural degeneration would not affect the audiogram, but likely contributes to age-related hearing impairment, especially in noisy environments. Thus, therapies designed to regrow peripheral axons could provide clinically meaningful improvement in the aged ear.
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Microglial cells are now recognized as the "gate-keepers" of healthy brain microenvironment with their disrupted functions adversely affecting neurovascular integrity, neuronal homeostasis, and network connectivity. The perception that these cells are purely toxic under neurodegenerative conditions has been challenged by a continuously increasing understanding of their complexity, the existence of a broad array of microglial phenotypes, and their ability to rapidly change in a context-dependent manner to attenuate or exacerbate injuries of different nature. ⋯ We further discuss context-dependent microglial contribution to neonatal brain injuries associated with prenatal and postnatal infection and inflammation, in relation to neurodevelopmental disorders, as well as perinatal hypoxia-ischemia and arterial focal stroke. We also emphasize microglial phenotypic diversity, notably at the ultrastructural level, and their sex-dependent influence on the pathophysiology of neurodevelopmental disorders.
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Over the past few decades, microglial cells have been regarded as the main executor of inflammation after acute and chronic central nervous system (CNS) disorders, responding rapidly to exogenous stimuli during acute trauma or infections, or signals released by cells undergoing cell death during conditions such as stroke, Alzheimer's disease (AD) and Parkinson's disease (PD). Barriers of the nervous system, and in particular the blood-brain barrier (BBB), play a key role in the normal physiological and cognitive functions of the brain. ⋯ This involves a dynamic response mediated by all components of the neurovascular unit (NVU), and ongoing research suggests that BBB-microglia interaction is critical to dictate the microglial response to NVU injury. The present review aims to give an up-to-date account of the emerging critical role of BBB-microglia interactions during neuroinflammation, and how these could be targeted for the therapeutic treatment of major central inflammatory disease.
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Microglia have long been recognized as the endogenous innate immune elements in the central nervous system (CNS) parenchyma. Besides fulfilling local immune-related functions, they provide cross-talk between the CNS and the immune system at large. ⋯ The full scale of their potential abilities has been highlighted by improvements in microglia isolation methods, the development of genetically tagged mouse models, advanced imaging technologies and the application of next-generation sequencing in recent years. Genome-wide expression analysis of relatively pure microglia populations from both mouse and human CNS tissues has thereby greatly contributed to our knowledge of their biology; what defines them under homeostatic conditions and how microglia respond to processes like aging and CNS disease? How and to what degree beneficial functions of microglia can be restored in the aged or diseased brain will be the key issue to be addressed in future research.
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The global burden of neurodegenerative disorders has increased substantially over the past 2 decades due to rising rates of population aging. Although neurodegenerative disorders differ in their clinical presentation, the underlying pathobiological processes are largely shared. Oxidative stress, among other mechanisms, is strongly implicated in neurodegenerative disorders and aging, and can potentially be targeted by antioxidative agents. ⋯ Furthermore, it stimulated the activities of antioxidant enzymes such as superoxide dismutase and glutathione peroxidase. In conclusion, curcumin appears to be a promising compound for phytomedicine. However, due to some concerns about its efficacy, further targeted experiments are needed to identify its exact molecular targets and pathways responsible for its antioxidant effects.