Dual roles of astrocytes in plasticity and reconstruction after traumatic brain injury

Abstract

Traumatic brain injury (TBI) is one of the leading causes of fatality and disability worldwide. Despite its high prevalence, effective treatment strategies for TBI are limited. Traumatic brain injury induces structural and functional alterations of astrocytes, the most abundant cell type in the brain. As a way of coping with the trauma, astrocytes respond in diverse mechanisms that result in reactive astrogliosis. Astrocytes are involved in the physiopathologic mechanisms of TBI in an extensive and sophisticated manner. Notably, astrocytes have dual roles in TBI, and some astrocyte-derived factors have double and opposite properties. Thus, the suppression or promotion of reactive astrogliosis does not have a substantial curative effect. In contrast, selective stimulation of the beneficial astrocytederived molecules and simultaneous attenuation of the deleterious factors based on the spatiotemporalenvironment can provide a promising astrocyte-targeting therapeutic strategy. In the current review, we describe for the first time the specific dual roles of astrocytes in neuronal plasticity and reconstruction, including neurogenesis, synaptogenesis, angiogenesis, repair of the blood-brain barrier, and glial scar formation after TBI. We have also classified astrocyte-derived factors depending on their neuroprotective and neurotoxic roles to design more appropriate targeted therapies.

The Increased Densities, But Different Distributions, of Both C3 and S100A10 Immunopositive Astrocyte-Like Cells in Alzheimer’s Disease Brains Suggest Possible Roles for Both A1 and A2 Astrocytes in the Disease Pathogenesis

“…This may possibly indicate that in AD following certain stimuli there is a "neurodestructive" process occurring via A1 astrocyte upregulation and activation primarily in the upper cortex and facilitated by the numbers of pre-existing "quiescent" A1 astrocytes (which in itself is possibly exacerbated with increasing age) followed by an upregulation and activation of A2 astrocytes in all areas in an attempt perhaps at belated neurotropic support and/or axonal repair. The concept of both a destructive and reparative role of astrocytes depending on the time course of a disease has been discussed by Zhou et al, with reference to traumatic brain injury [42]. Although the idea of a straightforward A1-toxic astrocyte role, and an A2 supportive role, is supported by studies in head trauma and PD [27,41], it has been somewhat complicated by the work of Hartmann et al [30].…”

Diabetes Mellitus-Related Dysfunction of the Motor System

“…However, in terms of surrounding environment, many of the brain environmental conditions caused by diabetes are thought to prevent the brain’s plasticity from recovering functions [ 217 ]. For example, astrocytes are critical for normal CNS function and play an important role in neuronal plasticity [ 218 , 219 ]. However, the cerebellum of 12-week STZ rats shows glial activation, cell death, and loss of glutamate transporters in astrocytes [ 220 ].…”

Persistent Neurovascular Unit Dysfunction: Pathophysiological Substrate and Trigger for Late-Onset Neurodegeneration After Traumatic Brain Injury

“…Through the glia limitans, astrocytes separate neurons from the blood vessels, meninges and perivascular spaces (Sofroniew, 2015). In addition to structural support for neurons, astrocytes also functionally favor neurons in a number of ways (Zhou et al, 2020), including regulating the neurotransmitter glutamate (Rothstein et al, 1996;Anderson and Swanson, 2000;Zou et al, 2010), releasing neurotrophic factors and gliotransmitters (Ye et al, 2003;Kardos et al, 2017;Perez et al, 2017), synthesizing glutamine, cholesterol, glutathione, and thrombospondin (Dringen et al, 2000;Slemmer et al, 2008;Colangelo et al, 2012), converting glucose into lactate (Magistretti and Pellerin, 1999;Danbolt, 2001;Magistretti, 2006), and controlling water homeostasis and neuronal activation (Lang et al, 1998;Walz, 2000;Kofuji and Newman, 2004;Jayakumar and Norenberg, 2010). Furthermore, the concentration of extracellular ions (Colangelo et al, 2012) and the glymphatic system (Jessen et al, 2015) are regulated by astrocytes.…”