Neural Stem Cells Transfected with Leukemia Inhibitory Factor Promote Neuroprotection in a Rat Model of Cerebral Ischemia

Neurosci Bull. 2019 Oct;35(5):901-908. doi: 10.1007/s12264-019-00405-5. Epub 2019 Jun 19.

Abstract

Leukemia inhibitory factor (LIF) contributes to the neuroprotection by neural stem cells (NSCs) after ischemic stroke. Our aim was to explore whether LIF-transfected NSCs (LIF-NSCs) can ameliorate brain injury and promote neuroprotection in a rat model of cerebral ischemia. To accomplish this goal, we transfected NSCs with a lentivirus carrying the LIF gene to stably overexpress LIF. The LIF-NSCs reduced caspase 3 activation under conditions of oxygen-glucose deprivation in vitro. Transient cerebral ischemia was induced in rats by 2 h of middle cerebral artery occlusion (MCAo), and LIF-NSCs were intravenously injected at 6 h post-ischemia. LIF-NSC treatment reduced the infarction volume and improved neurological recovery. Moreover, LIF-NSCs improved glial cell regeneration and ameliorated white matter injury in the MCAo rats. The NSCs acted as carriers and increased the expression of LIF in the lesions to protect against cerebral infarction, suggesting that LIF-NSCs could be a potential treatment for cerebral infarction.

Keywords: Cerebral ischemia; Infarction volume; Leukemia inhibitory factor; Neural stem cells; Neurological recovery.

MeSH terms

  • Animals
  • Brain Ischemia / genetics*
  • Brain Ischemia / pathology
  • Brain Ischemia / prevention & control
  • Disease Models, Animal
  • Leukemia Inhibitory Factor / genetics*
  • Male
  • Mice
  • Neural Stem Cells / physiology*
  • Neural Stem Cells / transplantation*
  • Neuroprotection / physiology*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Transfection / methods*

Substances

  • Leukemia Inhibitory Factor