Astrogliosis in CNS Pathologies: Is There A Role for Microglia?

Abstract

Astrogliosis, a cellular reaction with specific structural and functional characteristics, represents a remarkably homotypic response of astrocytes to all kinds of central nervous system (CNS) pathologies. Astrocytes play diverse functions in the brain, both harmful and beneficial. Mounting evidence indicates that astrogliosis is an underlying component of a diverse range of diseases and associated neuropathologies. The mechanisms that lead to astrogliosis are not fully understood, nevertheless, damaged neurons have long been reported to induce astrogliosis and astrogliosis has been used as an index for underlying neuronal damage. As the predominant source of proinflammatory factors in the CNS, microglia are readily activated under certain pathological conditions. An increasing body of evidence suggests that release of cytokines and other soluble products by activated microglia can significantly influence the subsequent development of astrogliosis and scar formation in CNS. It is well known that damaged neurons activate microglia very quickly, therefore, it is possible that activated microglia contribute factors/mediators through which damaged neuron induce astrogliosis. The hypothesis that activated microglia initiate and maintain astrogliosis suggests that suppression of microglial overactivation might effectively attenuate reactive astrogliosis. Development of targeted anti-microglial activation therapies might slow or halt the progression of astrogliosis and, therefore, help achieve a more beneficial environment in various CNS pathologies.

Reversal of Established Traumatic Brain Injury-Induced, Anxiety-Like Behavior in Rats after Delayed, Post-Injury Neuroimmune Suppression

“…28,82,83 Our IHC results support this time course, indicating injury-induced astrogliosis in the insula and amygdala at 6 months postinjury, but less activation of microglia (only significant in the amygdala), suggesting that microglial activation may precede astrocytic activation and modulate the onset and maintenance of astrogliosis. 27,[84][85][86][87][88] Lower levels of microglia expression could be the result of assessment at 6 months postinjury, when microglia may have returned to a quiescent or surveying state, 28,89 whereas astrocytic activation persists in a long-lasting, self-perpetuating…”

“…inflammatory response in the brain that exceeds early neuroprotection and results in neurodegenerative changes capable of continuing the inflammatory cycle. 9,27,90 Chronic inflammation has been observed in a number of studies examining patients with trauma-related anxiety disorders, reporting increases in downstream mediators, such as peripheral elevations of TNF-a, interferon-gamma (IFN-c), IL-1b, and IL-6, in patients with PTSD, [13][14][15][16] elevations of TNF-a and IL-6 in patients with OCD, 17 and elevations in proinflammatory cytokines and chemokines (monocyte chemoattractant protein 1, macrophage inflammatory protein 1 alpha, IL-1a, IL-1b, IL-6, IL-8, Eotaxin, granulocyte macrophage colony-stimulating factor, and IFN-c) in individuals with panic disorder and PTSD. 18 Despite compelling evidence implicating excessive inflammatory actions and a generalized inflammatory state in the development of anxiety disorders after TBI, central measures of proinflammatory cytokine elevations specifically related to human PTSD and other anxiety disorders have not yet been performed.…”

Neuroinflammation and Endoplasmic Reticulum Stress Are Coregulated by Crocin To Prevent Demyelination and Neurodegeneration

“…During EAE, neuroinflammation may drive ER stress, which was evident in astrocytes, as suggested by increased BiP immunostaining in EAE. Both apoptosis and astrogliosis are common outcomes to most neuroinflammatory diseases (63). Previous in vitro studies indicate that oligodendrocytes exposed to inflammatory proteins such as IFN-g exhibit features of ER stress (64), representing yet another link between ER stress and neuroinflammation.…”

Effects of 900MHz radiofrequency on corticosterone, emotional memory and neuroinflammation in middle-aged rats

“…These deficits include modified neurobiological parameters such as an increase in plasmatic levels of corticosterone (CORT), memory decline, elevation of interleukins (IL) levels, and astrocytes activation (Hayakawa et al, 2007;Lynch, 2010;Murray and Lynch, 1998). Cytokines, like the two immune mediators IL-1β and IL-6, are secreted by activated microglia and are known to trigger astrocytes activation (Woiciechowsky et al, 2004;Zhang et al, 2010). Astrocytes are non-neuronal central nervous system cells, implicated in neuronal synaptic plasticity (Vernadakis, 1996).…”