Differential susceptibility of cortical and subcortical inhibitory neurons and astrocytes in the long term following diffuse traumatic brain injury

Carron, Simone F.; Yan, Edwin BingBing; Alwis, Dasuni S.; Rajan, Ramesh

doi:10.1002/cne.24014

Cited by 31 publications

(47 citation statements)

References 143 publications

(203 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The co-localization ratios between Nav1.6 and other proteins including GFAP, nestin in the hippocampal subareas of CA1 and CA3 in 6 continuous sections near the KA injection site were also analyzed by using Image-Pro Plus software 6.0. The severity of astrogliosis was estimated to score GFAP immunoreactivity, grading into none (−), mild (+), moderate (++) or severe (+++) as previously described38.…”

Section: Methodsmentioning

confidence: 99%

Remarkable alterations of Nav1.6 in reactive astrogliosis during epileptogenesis

Zhao

Jiang

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Voltage-gated sodium channels (VGSCs) play a vital role in controlling neuronal excitability. Nav1.6 is the most abundantly expressed VGSCs subtype in the adult central nervous system and has been found to contribute to facilitate the hyperexcitability of neurons after electrical induction of status epilepticus (SE). To clarify the exact expression patterns of Nav1.6 during epileptogenesis, we examined the expression of Nav1.6 at protein and mRNA levels in two distinct animal models of temporal lobe epilepsy (TLE) including a post-SE model induced by kainic acid (KA) intrahippocampal injection and a kindling model evoked by pentylenetetrazole (PTZ). A prominent, seizure intensity-dependent increase of Nav1.6 expression in reactive astrocytes was observed in ipsilateral hippocampus of post-SE rats, reaching the peak at 21 days after SE, a time point during the latent stage of epileptogenesis. However, Nav1.6 with low expression level was selectively expressed in the hippocampal neurons rather than astrocytes in PTZ-kindled animals. This seizure-related increase of a VGSCs subtype in reactive astrocytes after SE may represent a new mechanism for signal communication between neuron and glia in the course of epileptogenesis, facilitating the neuronal hyperexcitability.

show abstract

Section: Methodsmentioning

confidence: 99%

Remarkable alterations of Nav1.6 in reactive astrogliosis during epileptogenesis

Zhao

Jiang

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The production of immunoreactive astrocytes during the pathogenesis of acute brain injuries (i.e. traumatic brain injury, ischemic stroke) has been extensively reported by anatomical and molecular techniques in several brain regions (8,13,48). In contrast, only few studies have explored the functional changes in the excitability of astrocytes following CNS injuries (13,49).…”

Section: Acute Traumatic Brain Injury Recruits Excitable Astrocytes Smentioning

confidence: 99%

TLR4-pathway impairs synaptic number and cerebrovascular functions through astrocyte activation following traumatic brain injury

Rosa

Farré‐Alins

Ortega

et al. 2020

Preprint

View full text Add to dashboard Cite

Activation of microglia and astrocytes contributes to synaptic remodeling, tissue repair and neuronal survival following traumatic brain injury (TBI). However, the consequences of the interaction between both glial cell types in rewiring neuronal networks and repairing brain functions remains poorly understood. Here, we explored how microglia-induced astrocyte activation modified synapses and cerebrovascular integrity following TBI. Calcium imaging experiments from brain slices revealed increased number of active astrocytes responding with spontaneous Ca 2+ events surrounding the injury at 1 d.a.i. These changes correlated with an increase in astrocytic GFAP-reactivity and microglia activation. Blocking microglia activation with the TLR4-blocker TAK242 reduced both the number of active and reactive astrocytes, suggesting a role for microglia in mediating astrocyte excitability. To determine the physiological consequences of microglia-induced astrocyte activation, we first quantified the number of synaptic puncta in TBI-mice treated with the TLR4-blocker. PSD-95/VGlut-1 staining showed that TAK-treatment reduced by half the synaptic loss observed in TBI-mice. Similar effects were also observed in the blood-brain barrier (BBB) integrity, in which blockage of microglia decreased Evans Blue extravasation, an indicative of preserved BBB. The acute effects of microglia inhibition on synapses and BBB were not observed in IP 3 R2 -/mice, indicating that the microglial effects depend on the subsequent astrocyte activation. In addition, acute TBI increases the release of the astrocytic-protein thrombospondin-1 (TSP-1) that seems to be necessary to modulate synaptic puncta in a sub-acute phase. Together, our data demonstrate that microglia-toastrocyte communication plays a crucial role in the pathophysiology of TBI and that its inhibition prevents the synaptic loss and BBB damage accelerating the recovery/repair of damaged tissue.Overall, our data indicates that targeting the microglia-astrocyte crosstalk might represent a therapeutic potential in CNS injuries and disorders.

show abstract

“…TBI has been associated with astrogliosis in subcortical regions (20). It has been proposed that this robust astrogliosis may be due to microvascular damage and acute disruption of the BBB (21).…”

Section: Discussionmentioning

confidence: 99%

A mouse Model of Focal Vascular Injury Induces Astrocyte Reactivity, Tau Oligomers, and Aberrant Behavior

et al. 2017

View full text Add to dashboard Cite

Neuropsychiatric symptom development has become more prevalent with 270,000 blast exposures occurring in the past 10 years in the United States. How blast injury leads to neuropsychiatric symptomology is currently unknown. Preclinical models of blast-induced traumatic brain injury have been used to demonstrate blood-brain barrier disruption, degenerative pathophysiology, and behavioral deficits. Vascular injury is a primary effect of neurotrauma that can trigger secondary injury cascades and neurodegeneration. Here we present data from a novel scaled and clinically relevant mouse blast model that was specifically developed to assess the outcome of vascular injury. We look at the biochemical effects and behavioral changes associated with blast injury in young-adult male BALB/c mice. We report that blast exposure causes focal vascular injury in the Somatosensory Barrel Field cortex, which leads to perivascular astrocyte reactivity, as well as acute aberrant behavior. Biochemical analysis revealed that mild blast exposure also invokes tauopathy, neuroinflammation, and oxidative stress. Overall, we propose our model to be used to evaluate focal blood-brain barrier disruption and to discover novel therapies for human neuropsychiatric symptoms.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

show abstract

Differential susceptibility of cortical and subcortical inhibitory neurons and astrocytes in the long term following diffuse traumatic brain injury

Cited by 31 publications

References 143 publications

Remarkable alterations of Nav1.6 in reactive astrogliosis during epileptogenesis

Remarkable alterations of Nav1.6 in reactive astrogliosis during epileptogenesis

TLR4-pathway impairs synaptic number and cerebrovascular functions through astrocyte activation following traumatic brain injury

A mouse Model of Focal Vascular Injury Induces Astrocyte Reactivity, Tau Oligomers, and Aberrant Behavior

Contact Info

Product

Resources

About