Antisense oligodeoxynucleotides targeting connexin43 reduce cerebral astrocytosis and edema in a rat model of traumatic brain injury

Z, Wu; Xu, Hao; He, Yalong; Yang, Guitao; Liao, Calvin C.Y.; Gao, Wei; Ming, Liang; He, Xiaosheng

doi:10.1179/1743132813y.0000000165

Cited by 11 publications

(12 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, it was reported that Cx43 blockage significantly reduced the degree of swelling after spinal cord injury (O'carroll et al, ). Also, down‐regulation of Cx43 reduced brain edema due to traumatic brain injury (Wu et al, ). As shown in the previous findings, Cx43 has very close relation with cerebral ischemia and brain edema.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that Cx43 heterozygous mice and Cx43 blockade promote neuron survival and inhibit apoptosis after cerebral ischemia (Xie et al, ; Davidson et al, ). Furthermore, it was reported that antisense oligodeoxynucleotides targeting Cx43 reduced cerebral astrocytosis and edema in traumatic brain injury model, suggesting close relationship between Cx43 and brain edema (Wu et al, ). Therefore, we speculate that the effects of PF and AS‐IV on ischemic edema may be dependent on Cx43.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Reduction of Ischemic Brain Edema by Combined use of Paeoniflorin and Astragaloside IV via Down‐Regulating Connexin 43

Chu

Huang

Gao

et al. 2017

Phytotherapy Research

View full text Add to dashboard Cite

Paeoniflorin (PF) and astragaloside IV (AS-IV) have protective effects on cerebral ischemia. We aimed to test the effects of combined use of PF and AS-IV on ischemic brain edema and investigate whether the effects were dependent on connexin43 (Cx43). We detected the expression of Cx43 induced by PF and AS-IV after cerebral ischemia. We also examined the effects of combined use of PF and AS-IV on ischemic edema and further investigated the related pathways. We demonstrated PF and AS-IV decreased Cx43 and aquaporin4 (AQP4) associating with reduction of brain edema by dry-wet weight and brain-specific gravity methods after cerebral ischemia. Administration of PF and AS-IV displayed a further attenuation of brain edema with lower Cx43 levels. Meanwhile, Cx43 blockade inhibited AQP4 down-regulation by the two drugs. Moreover, phosphorylation of C-Jun amino-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) were increased by PF and AS-IV, respectively. The effects of PF and AS-IV to down-regulate Cx43 were suppressed by JNK and ERK inhibitors, respectively. Our data indicate that PF and AS-IV alleviate ischemic brain edema, which has close relation to Cx43 down-regulation causing decrease of AQP4 via JNK and ERK pathways activation, respectively. Combined administration elicits synergistic effects on brain edema reduction. Copyright © 2017 John Wiley & Sons, Ltd.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Reduction of Ischemic Brain Edema by Combined use of Paeoniflorin and Astragaloside IV via Down‐Regulating Connexin 43

Chu

Huang

Gao

et al. 2017

Phytotherapy Research

View full text Add to dashboard Cite

show abstract

“…An upregulation or downregulation of Cx43 expression has been observed in reactive astrocytes, while activated microglia are primarily characterized by an induction of Cx43 expression [98,194,[350][351][352][353][354][355][356][357][358][359][360][361]. However, treatments that suppress Cx43-based communication can have different outcomes, i.e., they have been reported to be neuroprotective [337,[362][363][364] as well as neurotoxic [365,366] in different models of neurodegenerative conditions.…”

Section: Contribution Of Astroglial Connexins To Vasomotor Control Anmentioning

confidence: 99%

Connexin and pannexin signaling pathways, an architectural blueprint for CNS physiology and pathology?

Decrock

Bock

Wang

et al. 2015

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

The central nervous system (CNS) is composed of a highly heterogeneous population of cells. Dynamic interactions between different compartments (neuronal, glial, and vascular systems) drive CNS function and allow to integrate and process information as well as to respond accordingly. Communication within this functional unit, coined the neuro-glio-vascular unit (NGVU), typically relies on two main mechanisms: direct cell-cell coupling via gap junction channels (GJCs) and paracrine communication via the extracellular compartment, two routes to which channels composed of transmembrane connexin (Cx) or pannexin (Panx) proteins can contribute. Multiple isoforms of both protein families are present in the CNS and each CNS cell type is characterized by a unique Cx/Panx portfolio. Over the last two decades, research has uncovered a multilevel platform via which Cxs and Panxs can influence different cellular functions within a tissue: (1) Cx GJCs enable a direct cell-cell communication of small molecules, (2) Cx hemichannels and Panx channels can contribute to autocrine/paracrine signaling pathways, and (3) different structural domains of these proteins allow for channel-independent functions, such as cell-cell adhesion, interactions with the cytoskeleton, and the activation of intracellular signaling pathways. In this paper, we discuss current knowledge on their multifaceted contribution to brain development and to specific processes in the NGVU, including synaptic transmission and plasticity, glial signaling, vasomotor control, and blood-brain barrier integrity in the mature CNS. By highlighting both physiological and pathological conditions, it becomes evident that Cxs and Panxs can play a dual role in the CNS and that an accurate fine-tuning of each signaling mechanism is crucial for normal CNS physiology.

show abstract

“…Na + , Ca 2+ and H 2 O pass through Cx43 hemichannels and causes astrocytic swelling and cell death [88] . Down-regulation of Cx43 function reduced cell swelling and astrocytic death in a rat model of traumatic brain injury [89] . An in vitro experiment performed on acutely isolated hippocampal neurons showed that OGD induced a large inward current at the resting membrane potential [90] .…”

Section: Pannexin and Connexin Hemichannelsmentioning

confidence: 99%

Ionic Regulation of Cell Volume Changes and Cell Death after Ischemic Stroke

Song

2013

Transl. Stroke Res.

View full text Add to dashboard Cite

Stroke is a leading cause of human death and disability in the US and around the world. Shortly after the cerebral ischemia, cell swelling is the earliest morphological change in injured neuronal, glial and endothelial cells. Cytotoxic swelling directly results from increased Na+ (with H2O) and Ca2+ influx into cells via ionic mechanisms evoked by membrane depolarization and a number of harmful factors such as glutamate accumulation and the production of oxygen reactive species (ROS). During the sub-acute and chronic phases after ischemia, injured cells may show a phenotype of cell shrinkage due to complex processes involving membrane receptors/channels and programmed cell death signals. This review will introduce some progress in the understanding of the regulation of pathological cell volume changes and the involved receptors and channels, including NMDA and AMPA receptors, acid-sensing ion channels (ASIC), hemichannels, transient receptor potential (TRP) channels and KCNQ channels. Moreover, accumulating evidence supports a key role of energy deficiency and dysfunction of Na+/K+-ATPase in ischemia-induced cell volume changes and cell death. Specifically, the Na+ pump failure is a prerequisite for disruption of ionic homeostasis including a pro-apoptotic disruption of the K+ homeostasis. Finally, we will introduce the concept of hybrid cell death as a result of the Na+ pump failure in cultured cells and the ischemic brain. The goal of this review is to outline recent understanding of the ionic mechanism of ischemic cytoxicity and suggest innovative ideas for future translational research.

show abstract

Antisense oligodeoxynucleotides targeting connexin43 reduce cerebral astrocytosis and edema in a rat model of traumatic brain injury

Abstract: Antisense oligodeoxynucleotides targeting Cx43 reduced reactive astrocytosis and cerebral edema following TBI, indicating that Cx43 might be involved in regulating the water imbalance between brain cells.

Cited by 11 publications

References 22 publications

Reduction of Ischemic Brain Edema by Combined use of Paeoniflorin and Astragaloside IV via Down‐Regulating Connexin 43

Reduction of Ischemic Brain Edema by Combined use of Paeoniflorin and Astragaloside IV via Down‐Regulating Connexin 43

Connexin and pannexin signaling pathways, an architectural blueprint for CNS physiology and pathology?

Ionic Regulation of Cell Volume Changes and Cell Death after Ischemic Stroke

Contact Info

Product

Resources

About