Inhibition of Nkcc1 promotes axonal growth and motor recovery in ischemic rats

Mu, Xiaopeng; Wang, H.B.; Cheng, Xi; Yang, Lanxin; Sun, Xiaoyu; Qu, Huiling; Zhao, Shanshan; Zhou, Zhike; Liu, T.T.; Xiao, Ting; Song, Bing; Jolkkonen, Jukka; Zhao, Chuansheng

doi:10.1016/j.neuroscience.2017.09.036

Cited by 17 publications

(13 citation statements)

References 53 publications

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“…This is concordance with previous in vivo results showing a reduction in the infarction volume as well as in the ischemic necrotic cell death, especially remarkable when bumetanide was applied preinjury [60,63,67,68]. A recent study has shown that the inhibition of NKCC1 from day 7 post stroke enhanced axonal sprouting from uninjured neurons, resulting in a significant behavioral improvement [66].…”

Section: Cation-chloride Cotransporterssupporting

confidence: 92%

“…Contrary to what it was seen for NKCC1, the amount of KCC2 at both mRNA and protein levels was downregulated in both rat and mouse models of ischemic stroke [45,64,66,73,74]. Curiously, whereas the KCC2 levels in the plasma membrane are notably reduced 3 h post ischemia [74], there is a progressive decrease in the levels of total KCC2 given that it is significant on days 1 and 7 post stroke, but not at 2 h after injury [64].…”

Section: Cation-chloride Cotransportersmentioning

confidence: 86%

“…In contrast, the isoform KCC2 is the main one responsible for decreasing [Cl − ] i in mature neurons [26,58]. There is compelling evidence showing an increase in neuronal NKCC1 expression immediately after ischemic stroke, an event that contributes to cellular hyperexcitability and cell death [45,60,[63][64][65][66]. Wang and colleagues [60] have shown that NKCC1 is significantly upregulated in cortical neurons from 3 h to 48 h following focal cerebral ischemia in a rat model.…”

Section: Cation-chloride Cotransportersmentioning

confidence: 99%

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Symmetric and Asymmetric Synapses Driving Neurodegenerative Disorders

et al. 2021

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In 1959, E. G. Gray described two different types of synapses in the brain for the first time: symmetric and asymmetric. Later on, symmetric synapses were associated with inhibitory terminals, and asymmetric synapses to excitatory signaling. The balance between these two systems is critical to maintain a correct brain function. Likewise, the modulation of both types of synapses is also important to maintain a healthy equilibrium. Cerebral circuitry responds differently depending on the type of damage and the timeline of the injury. For example, promoting symmetric signaling following ischemic damage is beneficial only during the acute phase; afterwards, it further increases the initial damage. Synapses can be also altered by players not directly related to them; the chronic and long-term neurodegeneration mediated by tau proteins primarily targets asymmetric synapses by decreasing neuronal plasticity and functionality. Dopamine represents the main modulating system within the central nervous system. Indeed, the death of midbrain dopaminergic neurons impairs locomotion, underlying the devastating Parkinson’s disease. Herein, we will review studies on symmetric and asymmetric synapses plasticity after three different stressors: symmetric signaling under acute damage—ischemic stroke; asymmetric signaling under chronic and long-term neurodegeneration—Alzheimer’s disease; symmetric and asymmetric synapses without modulation—Parkinson’s disease.

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Section: Cation-chloride Cotransporterssupporting

confidence: 92%

Section: Cation-chloride Cotransportersmentioning

confidence: 86%

Section: Cation-chloride Cotransportersmentioning

confidence: 99%

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Symmetric and Asymmetric Synapses Driving Neurodegenerative Disorders

et al. 2021

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“…In models of neurodegenerative diseases, including 2VO, along with degeneration or elimination of fibres and synaptic contacts reflecting dysfunction [ 31 , 33 , 43 , 50 , 51 ], sprouting and mediator activation (hyperfunction) have been described [ 52 , 53 , 54 , 55 ]. Changes in mChAT and sChAT activity in response to in vivo influences are, as a rule, the equivalent of plastic changes in the cholinergic synaptic pool.…”

Section: Discussionmentioning

confidence: 99%

Cholinergic Internal and Projection Systems of Hippocampus and Neocortex Critical for Early Spatial Memory Consolidation in Normal and Chronic Cerebral Hypoperfusion Conditions in Rats with Different Abilities to Consolidation: The Role of Cholinergic Interneurons of the Hippocampus

et al. 2022

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The role of cholinergic projection systems of the neocortex and hippocampus in memory consolidation in healthy and neuropathological conditions has been subject to intensive research. On the contrary, the significance of cholinergic cortical and hippocampal interneurons in learning has hardly been studied. We aimed to evaluate the role of both cholinergic projection neurons and interneurons of the neocortex and hippocampus at an early stage of spatial memory consolidation (2s1) in normal and chronic brain hypoperfusion conditions. Control rats and rats subjected to permanent two-vessel occlusion were trained with the Morris water maze, and the activity of membrane-bound and water-soluble choline acetyltransferase was evaluated in the sub-fractions of ‘light’ and ‘heavy’ synaptosomes of the neocortex and hippocampus, in which the presynapses of cholinergic projections and interneurons, respectively, are concentrated. Animals were ranked into quartiles according to their performance on stage 2s1. We found: (1) quartile-dependent cholinergic composition of 2s1 function and dynamics of cholinergic synaptic plasticity under cerebral hypoperfusion; (2) cholinergic hippocampal interneurons are necessary for successful 2s1 consolidation; (3) cholinergic neocortical interneurons and projections can be critical for 2s1 consolidation in less learning rats. We conclude that targeted modulation of cholinergic synaptic activity in the hippocampus and neocortex can be effective in reversing the cognitive disturbance of cerebral hypoperfusion. We discuss the possible ways to restore the impaired spatial memory 2s1 in the presence of cerebral hypoperfusion.

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“…Activated GABA inhibits axonal regeneration by stimulating the Rho/Rock signaling pathway and p75NTR synthesis, increasing cell death [ 83 , 84 ]. It also inhibits GABA stimulation, Rho/Rock signaling and p75NTR levels, reducing cell death, accelerating regeneration and increasing endogenous BDNF levels [ 85 ]. Moreover, co-treatment with dexamethasone, which possesses antiedematous activity, and bumetanide, which blocks the aquaporin 1 receptor and also decreases edema, exerts a synergistic inhibitory effect on the edema that develops after peripheral nerve regeneration and healing [ 86 ].…”

Section: Medicationsmentioning

confidence: 99%

Potential Therapeutic Strategies and Substances for Facial Nerve Regeneration Based on Preclinical Studies

Yoo

Chon

Jung

et al. 2021

IJMS

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Despite advances in microsurgical technology and an improved understanding of nerve regeneration, obtaining satisfactory results after facial nerve injury remains a difficult clinical problem. Among existing peripheral nerve regeneration studies, relatively few have focused on the facial nerve, particularly how experimental studies of the facial nerve using animal models play an essential role in understanding functional outcomes and how such studies can lead to improved axon regeneration after nerve injury. The purpose of this article is to review current perspectives on strategies for applying potential therapeutic methods for facial nerve regeneration. To this end, we searched Embase, PubMed, and the Cochrane library using keywords, and after applying exclusion criteria, obtained a total of 31 qualifying experimental studies. We then summarize the fundamental experimental studies on facial nerve regeneration, highlighting recent bioengineering studies employing various strategies for supporting facial nerve regeneration, including nerve conduits with stem cells, neurotrophic factors, and/or other therapeutics. Our summary of the methods and results of these previous reports reveal a common feature among studies, showing that various neurotrophic factors arising from injured nerves contribute to a microenvironment that plays an important role in functional recovery. In most cases, histological examinations showed that this microenvironmental influence increased axonal diameter as well as myelination thickness. Such an analysis of available research on facial nerve injury and regeneration represents the first step toward future therapeutic strategies.

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Inhibition of Nkcc1 promotes axonal growth and motor recovery in ischemic rats

Cited by 17 publications

References 53 publications

Symmetric and Asymmetric Synapses Driving Neurodegenerative Disorders

Symmetric and Asymmetric Synapses Driving Neurodegenerative Disorders

Cholinergic Internal and Projection Systems of Hippocampus and Neocortex Critical for Early Spatial Memory Consolidation in Normal and Chronic Cerebral Hypoperfusion Conditions in Rats with Different Abilities to Consolidation: The Role of Cholinergic Interneurons of the Hippocampus

Potential Therapeutic Strategies and Substances for Facial Nerve Regeneration Based on Preclinical Studies

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