AAV9-mediated KCC2 upregulation enhances functional recovery following cervical spinal cord injury Article Swipe
Mohammad-Masoud Zavvarian
,
Akshat D. Modi
,
Mohammad Rasool Khazaei
,
Zixiang Luo
,
Alexander A. Velumian
,
Omar Imad Hassan
,
James Hong
,
Christopher S. Ahuja
,
Zeenal H. Patel
,
Miao He
,
Zhigang He
,
Michael G. Fehlings
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1038/s42003-025-08734-0
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1038/s42003-025-08734-0
Following traumatic cervical spinal cord injury (SCI), injury-induced functional changes within the perilesional forelimb circuits are an important cause of neurological dysfunction. K+/Cl- cotransporter 2 (KCC2) is a neuron-specific transmembrane protein essential for inhibitory neurotransmission. Reduced KCC2 expression post-SCI disrupts the excitatory/inhibitory ratio in spinal interneurons and blocks supraspinal neurotransmission. Recent advances in AAV9-based gene therapies present a promising approach to upregulate KCC2 and restore functional communication in the injured spinal circuits. This study aims to characterize the neurophysiological changes in a rodent model of bilateral contusion-compression cervical SCI and to assess the functional impact of KCC2 gene therapy in the injured spinal cord. We demonstrate that intrathecal AAV9 delivery of KCC2 enhances long-term forelimb and hindlimb motor recovery and improves neurophysiological outcomes following cervical SCI. This is accompanied by Luminex assay, transcriptional analysis, and immunohistochemical observations suggesting improvements in neuroanatomical preservation and neuroglial alterations in the perilesional circuits.
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- en
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- https://doi.org/10.1038/s42003-025-08734-0
- OA Status
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- References
- 93
- OpenAlex ID
- https://openalex.org/W4415377171
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https://openalex.org/W4415377171Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1038/s42003-025-08734-0Digital Object Identifier
- Title
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AAV9-mediated KCC2 upregulation enhances functional recovery following cervical spinal cord injuryWork title
- Type
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articleOpenAlex work type
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enPrimary language
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2025Year of publication
- Publication date
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2025-10-21Full publication date if available
- Authors
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Mohammad-Masoud Zavvarian, Akshat D. Modi, Mohammad Rasool Khazaei, Zixiang Luo, Alexander A. Velumian, Omar Imad Hassan, James Hong, Christopher S. Ahuja, Zeenal H. Patel, Miao He, Zhigang He, Michael G. FehlingsList of authors in order
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https://doi.org/10.1038/s42003-025-08734-0Publisher landing page
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://doi.org/10.1038/s42003-025-08734-0Direct OA link when available
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0Total citation count in OpenAlex
- References (count)
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93Number of works referenced by this work
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| abstract_inverted_index.interneurons | 45 |
| abstract_inverted_index.neurological | 20 |
| abstract_inverted_index.observations | 136 |
| abstract_inverted_index.perilesional | 12, 147 |
| abstract_inverted_index.preservation | 141 |
| abstract_inverted_index.communication | 66 |
| abstract_inverted_index.cotransporter | 23 |
| abstract_inverted_index.transmembrane | 29 |
| abstract_inverted_index.injury-induced | 7 |
| abstract_inverted_index.neuroanatomical | 140 |
| abstract_inverted_index.neuron-specific | 28 |
| abstract_inverted_index.transcriptional | 132 |
| abstract_inverted_index.neurophysiological | 78, 121 |
| abstract_inverted_index.neurotransmission. | 34, 49 |
| abstract_inverted_index.immunohistochemical | 135 |
| abstract_inverted_index.contusion-compression | 86 |
| abstract_inverted_index.excitatory/inhibitory | 41 |
| abstract_inverted_index.K<sup>+</sup>/Cl<sup>-</sup> | 22 |
| cited_by_percentile_year | |
| corresponding_author_ids | https://openalex.org/A5047977949 |
| countries_distinct_count | 2 |
| institutions_distinct_count | 12 |
| corresponding_institution_ids | https://openalex.org/I185261750 |
| citation_normalized_percentile.value | 0.6721798 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |