In Vivo Local Administration of Para-Amino-Bebblistatin to the Injured Spinal Cord Fails to Improve the NaChBac-Expressing DRGs Transplantation Article Swipe
Sonia Hingorani Jai Prakash
,
Guillem Paniagua
,
Carlos Sánchez-Huertas
,
Victoria Moreno‐Manzano
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3390/ijms262110479
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3390/ijms262110479
Spinal cord injury (SCI) is a devastating, debilitating, and life-altering condition that lacks a cure or effective treatment as of today. An altered excitation/inhibition ratio after an injury, with an increase in inhibitory input, limits motor and sensory function. Together with the limited endogenous regeneration capacity of the affected neuronal circuits, this results in further loss of function. Hingorani and collaborators recently reported that transplantation of dissociated sensory neurons from neonatal dorsal root ganglia (DRGs) expressing the bacterial sodium channel NaChBac significantly improved locomotion in a severe SCI by increasing the excitatory neuronal input at the injury site. Here, we additionally target the potential axonal regeneration of endogenous and transplanted cells, using cytoskeleton-modulating drugs to enhance axonal length. We employ, alone or in combination, blebbistatin and epothilone B, tested in vitro. We found that individually, each compound significantly induced the sensory neurons’ axonal elongation; however, their combination completely abolished it. Interestingly, a combinatory treatment including the modification of DRGs to express the NaChBac sodium channel and the treatment with blebbistatin increased the axonal elongation in vitro. Nevertheless, when applied in vivo in a model of SCI, local and single para-amino-blebbistatin (a stable analogue of blebbistatin) administration and the transplanted NaChBac expressing sensory neurons limit the functional recovery enabled by neuronal transplantation alone. Thus, despite the beneficial outputs of isolated neuronal cultures that allow selection of in vivo combinatory strategies, the multifaced characteristics of CNS injuries limit the potential success of single and local treatment administration, demanding extended and sustained treatments.
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- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/ijms262110479
- https://www.mdpi.com/1422-0067/26/21/10479/pdf?version=1761663588
- OA Status
- gold
- References
- 28
- OpenAlex ID
- https://openalex.org/W4415624216
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https://openalex.org/W4415624216Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.3390/ijms262110479Digital Object Identifier
- Title
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In Vivo Local Administration of Para-Amino-Bebblistatin to the Injured Spinal Cord Fails to Improve the NaChBac-Expressing DRGs TransplantationWork title
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articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
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2025Year of publication
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2025-10-28Full publication date if available
- Authors
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Sonia Hingorani Jai Prakash, Guillem Paniagua, Carlos Sánchez-Huertas, Victoria Moreno‐ManzanoList of authors in order
- Landing page
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https://doi.org/10.3390/ijms262110479Publisher landing page
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https://www.mdpi.com/1422-0067/26/21/10479/pdf?version=1761663588Direct link to full text PDF
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goldOpen access status per OpenAlex
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https://www.mdpi.com/1422-0067/26/21/10479/pdf?version=1761663588Direct OA link when available
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