Neuroprotective and regenerative roles of intranasal Wnt-3a administration after focal ischemic stroke in mice

作者：Wei, Zheng Zachory; Zhang, James Ya; Taylor, Tammi M.; Gu, Xiaohuan; Zhao, Yingying; Wei, Ling^*

来源：Journal of Cerebral Blood Flow and Metabolism, 2018, 38(3): 404-421.

DOI：10.1177/0271678X17702669

• Ischemic stroke
• Wnt-3a
• neuroprotection
• neurogenesis
• subventricular zone
• sensorimotor function

Wnt signaling is a conserved pathway involved in expansion of neural progenitors and lineage specification during development. However, the role of Wnt signaling in the post-stroke brain has not been well-elucidated. We hypothesized that Wnt-3a would play an important role for neurogenesis and brain repair. Adult male mice were subjected to a focal ischemic stroke targeting the sensorimotor cortex. Mice that received Wnt-3a (2 mg/kg/day, 1 h after stroke and once a day for the next 2 days, intranasal delivery) had reduced infarct volume compared to stroke controls. Wnt-3a intranasal treatment of seven days upregulated the expression of brain-derived growth factor (BDNF), increased the proliferation and migration of neuroblasts from the subventricular zone (SVZ), resulting in increased numbers of newly formed neurons and endothelial cells in the peri-infarct zone. Both the molecular and cellular effects of Wnt-3a were blocked by the Wnt specific inhibitors XAV-939 or Dkk-1. In functional assays, Wnt-3a treatment enhanced the local cerebral blood flow (LCBF) in the peri-infarct, as well as improved sensorimotor functions in a battery of behavioral tests. Together, our data demonstrates that the Wnt-3a signaling can act as a dual neuroprotective and regenerative factor for the treatment of ischemic stroke.

• 出版日期2018-3
• 单位首都医科大学