Neuroprotective effects of lentivirus-mediated aquaporin-4 gene silencing in rat model of traumatic brain injury

Neurol Res. 2022 Aug;44(8):692-699. doi: 10.1080/01616412.2022.2039509. Epub 2022 Feb 21.

Abstract

Background: Traumatic brain injury (TBI) is a common clinical condition caused by external force. Aquaporin-4 (AQP4) in astrocytes participates in the generation of cell swelling in TBI.

Methods: This research explored the effect of AQP4 gene silencing in a TBI rat model. A hydraulic craniocerebral trauma instrument was employed for establishing the TBI rat model. AQP4 expression in the brain was inhibited by the injection of AQP4 shRNA-lentiviral vector. The expression of relative genes was evaluated by Western blot and qRT-PCR. Neuronal apoptosis was analyzed by TUNEL assay.

Results: AQP4 shRNA treatment inhibited AQP4 expression in the brain of rats with TBI. AQP4 shRNA alleviated TBI-induced brain edema and neurological deficit in rats. Neuronal apoptosis and astrocyte activation in TBI rats were reduced by AQP4 silencing.

Conclusion: This research demonstrated that AQP4 shRNA-induced silencing of AQP4 in the TBI rat model reduced the expression of AQP4 and GFAP, alleviated brain edema, neurological deficit, neuronal apoptosis and inhibited astrocyte activation.

Keywords: Aquaporin-4; rat; shRNA; traumatic brain injury.

MeSH terms

  • Animals
  • Aquaporin 4* / genetics
  • Astrocytes
  • Brain Edema* / etiology
  • Brain Edema* / metabolism
  • Brain Injuries, Traumatic* / genetics
  • Brain Injuries, Traumatic* / therapy
  • Gene Silencing
  • Lentivirus / genetics
  • Lentivirus / metabolism
  • Neuroprotection
  • RNA, Small Interfering
  • Rats

Substances

  • Aqp4 protein, rat
  • Aquaporin 4
  • RNA, Small Interfering