Morphological and functional alterations of astrocytes responding to traumatic brain injury

Cheng, Xinbin; Wang, Jin; Xiao, Sun; Shao, Lishi; Guo, Zeyun; Li, Yang

doi:10.31083/j.jin.2019.02.110

Cited by 22 publications

(6 citation statements)

References 104 publications

(111 reference statements)

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“…CBD also decreases mitochondrial dysfunction associated with neuroinflammation [91]. Another possibility to explain the long-term protective effect found in the present study is that CBD avoids the TBI-induced dysregulation of glutamate uptake in astrocytes [61][62][63]. Overall, it is possible to indicate that CBD-induced effects result in long-term functional improvement after trauma.…”

Section: Discussionsupporting

confidence: 55%

“…The immediate increase in extracellular glutamate levels after severe TBI may be caused by the primary injury that favors the rupture of vessels, neurons, and BBB, facilitating the release of intracellular contents into the parenchyma [59,60]. On the other hand, persistent high glutamate release for several hours and days after TBI may result from dysregulation of glutamate reuptake in astrocytes by chronic dysfunction in astrocytic transporters (GLAST/GLT1) [61,62]. Indeed, experimental evidence supports the downregulation of GLUT-1 transporters 7 days post-TBI [63].…”

Section: Discussionmentioning

confidence: 99%

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Cannabidiol Reduces Short- and Long-Term High Glutamate Release after Severe Traumatic Brain Injury and Improves Functional Recovery

et al. 2022

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This study aimed to determine if orally administered cannabidiol (CBD) lessens the cortical over-release of glutamate induced by a severe traumatic brain injury (TBI) and facilitates functional recovery. The short-term experiment focused on identifying the optimal oral pretreatment of CBD. Male Wistar rats were pretreated with oral administration of CBD (50, 100, or 200 mg/kg) daily for 7 days. Then, extracellular glutamate concentration was estimated by cortical microdialysis before and immediately after a severe TBI. The long-term experiment focused on evaluating the effect of the optimal treatment of CBD (pre- vs. pre- and post-TBI) 30 days after trauma. Sensorimotor function, body weight, and mortality rate were evaluated. In the short term, TBI induced a high release of glutamate (738% ± 173%; p < 0.001 vs. basal). Oral pretreatment with CBD at all doses tested reduced glutamate concentration but with higher potency at when animals received 100 mg/kg (222 ± 33%, p < 0.01 vs. TBI), an effect associated with a lower mortality rate (22%, p < 0.001 vs. TBI). In the long-term experiment, the TBI group showed a high glutamate concentration (149% p < 0.01 vs. SHAM). In contrast, animals receiving the optimal treatment of CBD (pre- and pre/post-TBI) showed glutamate concentrations like the SHAM group (p > 0.05). This effect was associated with high sensorimotor function improvement. CBD pretreatment, but not pre-/post-treatment, induced a higher body weight gain (39% ± 2.7%, p < 0.01 vs. TBI) and lower mortality rate (22%, p < 0.01 vs. TBI). These results support that orally administered CBD reduces short- and long-term TBI-induced excitotoxicity and facilitated functional recovery. Indeed, pretreatment with CBD was sufficient to lessen the adverse sequelae of TBI.

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Cannabidiol Reduces Short- and Long-Term High Glutamate Release after Severe Traumatic Brain Injury and Improves Functional Recovery

et al. 2022

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“…These changes suggest that reactive juxtavascular astrocytes are more often turning into a more immature state with non-passive current patterns. Thus, the heterogeneity of astrocytes already observed prior to injury, for example, by morphology and gene expression (Batiuk et al, 2020;Bayraktar et al, 2020;Cheng et al, 2019;Cragnolini, Montenegro, Friedman, & Masco, 2018;Lanjakornsiripan et al, 2018;Magaki, Williams, & Vinters, 2018;Morel et al, 2017;Westergard & Rothstein, 2020), further increases after injury such that predominantly juxtavascular astrocytes show loss of K ir 4.1 immunostaining and non-passive properties.…”

Section: Discussionmentioning

confidence: 98%

Heterogeneity of astrocytes: Electrophysiological properties of juxtavascular astrocytes before and after brain injury

Götz

Bribián

López‐Mascaraque

et al. 2020

Glia

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Astrocyte heterogeneity is increasingly recognized, but still little is known about juxtavascular astrocytes with their somata directly adjacent to blood vessels, despite their importance after brain injury. As juxtavascular astrocytes originate from common progenitor cells, that is, have a clonal origin, they may intrinsically differ from other, nonjuxtavascular astrocytes. To explore this, we examined the electrophysiological properties of these groups of astrocytes and the underlying ion channels. Using brain slices of BAC Aldh1l1-eGFP transgenic mice with astrocytes labeled by GFP expression, we compared juxtavascular and non-juxtavascular astrocytes in the somatosensory cortex by means of whole-cell patch-clamp recordings and immunohistochemical staining. Prior to injury, juxta-and non-juxtavascular astrocytes exhibit comparable electrophysiological properties with characteristic mostly passive conductance and a typical negative resting membrane potential. Immunohistochemical analysis of K + channels showed that all astrocytes were K ir 4.1 + , but revealed an intriguing difference for K v 4.3. The expression of K v 4.3 in sibling astrocytes (non-juxtavascular, juxtavascular and pial) was dependent on their ontogenetic origin with lowest levels in juxtavascular astrocytes located in upper cortical layers. After traumatic brain injury (TBI), we found profound changes in the electrophysiological type of astrocytes with a predominance of non-passive properties and this pattern was significantly enriched in juxtavascular astrocytes. This was accompanied by pronounced down-regulation of K ir 4.1 in proliferating astrocytes, which was significantly more in juxtavascular compared to non-juxtavascular astrocytes. Taken together, TBI induces profound differences in electrophysiological properties between juxtavascular and non-juxtavascular astrocytes that might be related to the preponderance of juxtavascular astrocyte proliferation.

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“…Reactive astrogliosis has always been accompanied by varying degrees of cellular hypertrophy [76]. In terms of function, reactive astrocytes can absorb glutamate from the synaptic cleft, not only reducing excitotoxicity but also providing cells with the substances required for neuronal metabolism [77]. Therefore, astrocytes may be activated by fluoxetine treatment to cope with the increased neuronal production that occurs after treatment with this AD, thus responding to the network changes and assuming a role.…”

Section: Discussionmentioning

confidence: 99%

Beyond New Neurons in the Adult Hippocampus: Imipramine Acts as a Pro-Astrogliogenic Factor and Rescues Cognitive Impairments Induced by Stress Exposure

Machado-Santos

Loureiro‐Campos

Patrício

et al. 2022

Cells

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Depression is a prevalent, socially burdensome disease. Different studies have demonstrated the important role of astrocytes in the pathophysiology of depression as modulators of neurotransmission and neurovascular coupling. This is evidenced by astrocyte impairments observed in brains of depressed patients and the appearance of depressive-like behaviors upon astrocytic dysfunctions in animal models. However, little is known about the importance of de novo generated astrocytes in the mammalian brain and in particular its possible involvement in the precipitation of depression and in the therapeutic actions of current antidepressants (ADs). Therefore, we studied the modulation of astrocytes and adult astrogliogenesis in the hippocampal dentate gyrus (DG) of rats exposed to an unpredictable chronic mild stress (uCMS) protocol, untreated and treated for two weeks with antidepressants—fluoxetine and imipramine. Our results show that adult astrogliogenesis in the DG is modulated by stress and imipramine. This study reveals that distinct classes of ADs impact differently in the astrogliogenic process, showing different cellular mechanisms relevant to the recovery from behavioral deficits induced by chronic stress exposure. As such, in addition to those resident, the newborn astrocytes in the hippocampal DG might also be promising therapeutic targets for future therapies in the neuropsychiatric field.

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Morphological and functional alterations of astrocytes responding to traumatic brain injury

Cited by 22 publications

References 104 publications

Cannabidiol Reduces Short- and Long-Term High Glutamate Release after Severe Traumatic Brain Injury and Improves Functional Recovery

Cannabidiol Reduces Short- and Long-Term High Glutamate Release after Severe Traumatic Brain Injury and Improves Functional Recovery

Heterogeneity of astrocytes: Electrophysiological properties of juxtavascular astrocytes before and after brain injury

Beyond New Neurons in the Adult Hippocampus: Imipramine Acts as a Pro-Astrogliogenic Factor and Rescues Cognitive Impairments Induced by Stress Exposure

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