Inhibitory role of lentivirus-mediated aquaporin-4 gene silencing in the formation of glial scar in a rat model of traumatic brain injury.

Yong, Ya-Xiong; Li, Yu-Ming; Lian, Jia; Luo, Chuan-Ming; Zhong, De-Xia; Han, Ke

Yong, Ya-Xiong; Li, Yu-Ming; Lian, Jia; Luo, Chuan-Ming; Zhong, De-Xia; Han, Ke.

Afiliación

Yong YX; Department of Neurology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China.
Li YM; Department of Neurosurgery, First Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Lian J; Department of Neurology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China.
Luo CM; Department of Neurology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China.
Zhong DX; Department of Neurology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China.
Han K; Department of Neurology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China.

J Cell Biochem ; 120(1): 368-379, 2019 01.

Article en En | MEDLINE | ID: mdl-30246455

RESUMEN

Traumatic brain injury (TBI), an acute degenerative pathology of the central nervous system, is a leading cause of death and disability. As the glial scar is a mechanical barrier to nerve regeneration, inhibitory molecules in the forming scar and methods to overcome them have suggested molecular modification strategies to allow neuronal growth and functional regeneration. Herein, we aim to investigate the effects of aquaporin-4 (AQP4) gene silencing on the glial scar formation after TBI by establishing rat models. After modeling, TBI rats were transfected with AQP4 small hairpin RNA [shRNA] (AQP4 gene silencing by lentiviral vector-delivered shRNA) and empty vectors, respectively. Neurological functions of the rats were evaluated after TBI. The hematoxylin and eosin staining was conducted to observe histomorphological changes in rat brain tissues. The messenger RNA (mRNA) and protein expressions of glial fibrillary acidic protein (GFAP), vimentin, fibronectin, laminin, and AQP4 were measured by reverse transcription-quantitative polymerase chain reaction and Western blot analysis. The ratio of positive expression area was calculated, and the glial scar was observed by immunohistochemistry. At the 7th, 14th, and 28th days after TBI, TBI rats treated with AQP4 shRNA showed improved neurological function and lessened histomorphological changes. AQP4 gene silencing mediated by lentivirus decreased the mRNA and protein expressions of GFAP, vimentin, fibronectin, and laminin, the number of positive cells, the ratio of positive expression area, and the glial scar. Our study demonstrates that lentivirus-mediated AQP4 gene silencing could inhibit the formation of glial scar after TBI, which is beneficial to the recovery of neurological function.

Asunto(s)

Acuaporina 4/genética; Lesiones Traumáticas del Encéfalo/terapia; Cicatriz/terapia; Silenciador del Gen; Neuroglía/metabolismo; Animales; Acuaporina 4/metabolismo; Lesiones Traumáticas del Encéfalo/patología; Cicatriz/genética; Cicatriz/metabolismo; Modelos Animales de Enfermedad; Fibronectinas/genética; Fibronectinas/metabolismo; Proteína Ácida Fibrilar de la Glía/genética; Proteína Ácida Fibrilar de la Glía/metabolismo; Laminina/genética; Laminina/metabolismo; Lentivirus; Masculino; Examen Neurológico; ARN Mensajero/metabolismo; ARN Interferente Pequeño/genética; Ratas; Ratas Sprague-Dawley; Transfección; Vimentina/genética; Vimentina/metabolismo

Palabras clave

aquaporin-4 (AQP4); gene silencing; glial scar; traumatic brain injury (TBI)

Texto completo

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neuroglía / Cicatriz / Silenciador del Gen / Acuaporina 4 / Lesiones Traumáticas del Encéfalo Límite: Animals Idioma: En Revista: J Cell Biochem Año: 2019 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos

Texto completo

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Buscar en Google