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Overexpressed ski efficiently promotes neurorestoration, increases neuronal regeneration, and reduces astrogliosis after traumatic brain injury
Ist Teil von
Gene therapy, 2023-02, Vol.30 (1-2), p.75-87
Ort / Verlag
London: Nature Publishing Group UK
Erscheinungsjahr
2023
Quelle
MEDLINE
Beschreibungen/Notizen
Traumatic brain injury (TBI) survivors suffer from long-term disability and neuropsychiatric sequelae due to irreparable brain tissue destruction. However, there are still few efficient therapies to promote neurorestoration in damaged brain tissue. This study aimed to investigate whether the pro-oncogenic gene
ski
can promote neurorestoration after TBI. We established a
ski
-overexpressing experimental TBI mouse model using adenovirus-mediated overexpression through immediate injection after injury. Hematoxylin-eosin staining, MRI-based 3D lesion volume reconstruction, neurobehavioral tests, and analyses of neuronal regeneration and astrogliosis were used to assess neurorestorative efficiency. The effects of
ski
overexpression on the proliferation of cultured immature neurons and astrocytes were evaluated using imaging flow cytometry. The Ski protein level increased in the perilesional region at 3 days post injury.
ski
overexpression further elevated Ski protein levels up to 14 days post injury. Lesion volume was attenuated by approximately 36–55% after
ski
overexpression, with better neurobehavioral recovery, more newborn immature and mature neurons, and less astrogliosis in the perilesional region. Imaging flow cytometry results showed that
ski
overexpression elevated the proliferation rate of immature neurons and reduced the proliferation rate of astrocytes. These results show that
ski
can be considered a novel neurorestoration-related gene that effectively promotes neurorestoration, facilitates neuronal regeneration, and reduces astrogliosis after TBI.