Evidence map›Paper›PMID 41359836›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

Functional recovery induced by KCC2-enabled relay pathways in completely injured spinal cords in adult rats.

Yaxian Wang, Fenglan Liu, Qi Shan, Xuzhaoyu Wang, Wei Liu, Xinxin Chen, Cheng Teng, Yehua Lv, Xiaosong Gu, Xuhua Wang and 1 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Yaxian Wang *Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.ORCID 0000-0001-5854-9352
Fenglan Liu *Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
Qi Shan *Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.ORCID 0000-0001-7924-1234
Xuzhaoyu WangKey Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
Wei LiuKey Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.ORCID 0000-0002-9742-8139
Xinxin ChenKey Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
Cheng TengKey Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
Yehua LvKey Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
Xiaosong GuKey Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
Xuhua WangNanhu Brain-computer Interface Institute, Hangzhou, Zhejiang Province 311100, People's Republic of China.ORCID 0000-0002-4565-787X
Bin YuKey Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.ORCID 0000-0002-8927-3333

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Despite tremendous progress in promoting endogenous axon regeneration and engineering relay pathways by cell transplantation, the obtained functional recovery is still limited. We reason that these regenerated connections might not be able to integrate into the functional circuits in injured spinal cord. In this study, we tested whether modulating the neuronal excitability by pharmacological potassium-chloride cotransporter (KCC2) activation could enhance the functional outcomes of these regenerative treatments in a complete spinal cord injury (SCI) in adult rats. We found that while osteopontin/insulin-like growth factor 1 overexpression (to enhance axon regeneration) or neural stem cell (NSC) transplantation (to build a relay) alone failed to restore the interrupted spinal circuitry, the double treatment facilitated the integration of NSCs into the host spinal network, significantly promoting axonal regeneration and synapse formation. Behavioral assessments demonstrated that the addition of CLP290, a KCC2 agonist, to the combined treatment markedly improved hindlimb locomotion, as evidenced by higher Basso, Beattie and Bresnahan (BBB) scores and enhanced joint oscillation in fine locomotion analysis. Consistently, electrophysiological evaluations indicated partial restoration of electrical transmission through the reconstructed spinal network. Our findings highlight the synergistic effects of KCC2-mediated neuronal modulation on promoting functional recovery after complete SCI.

Indexed as

Recovery of FunctionSpinal Cord InjuriesSymportersAnimalsAxonsFemaleInsulin-Like Growth Factor IK Cl- CotransportersLocomotionNerve RegenerationNeural Stem CellsOsteopontinRatsRats, Sprague-DawleyInsulin-Like Growth Factor IK Cl- CotransportersOsteopontinSymporterscombined strategiesKCC2-enabled relay pathwaysspinal cord injury

Identifiers

PMID41359836
PMCPMC12718361

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.