1. Academic Validation
  2. Teriparatide induces angiogenesis in ischemic cerebral infarction zones of rats through AC/PKA signaling and reduces ischemia-reperfusion injury

Teriparatide induces angiogenesis in ischemic cerebral infarction zones of rats through AC/PKA signaling and reduces ischemia-reperfusion injury

  • Biomed Pharmacother. 2022 Apr;148:112728. doi: 10.1016/j.biopha.2022.112728.
Moliang Xiong 1 Yun Feng 2 Shujie Huang 1 Siyuan Lv 1 Yuhao Deng 1 Min Li 1 Pengfei Wang 1 Minjie Luo 1 Huangtao Wen 1 Wangming Zhang 3
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Guangzhou 510282, China.
  • 2 Department of Pediatrics, Hospital of the 74th Group Army of the Chinese people's Liberation Army, Guangzhou 510282, China.
  • 3 Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Guangzhou 510282, China. Electronic address: wzhang@vip.126.com.
Abstract

Teriparatide is a commonly used drug indicated for the treatment of osteoporosis in postmenopausal women. Teriparatide can also upregulate ANG-1 expression through the AC/PKA signaling pathway to promote angiogenesis. At present, promoting angiogenesis is a promising but unrealized strategy for the treatment of ischemic cerebral infarction. However, there are few studies on the application of teriparatide in the treatment of cerebral infarction. We used teriparatide to treat ischemic cerebral infarction in rats and obtained three major findings. First, teriparatide can promote angiogenesis, reduce cerebral infarct size, and increase cerebral perfusion by upregulating ANG-1 expression. Second, teriparatide can promote the expression of HO1, SOD2 and inhibit the production of pro-inflammatory cytokines IL-1β, IL-6 by upregulating Nrf2 expression. Third, we further found that teriparatide can mitigate blood-brain barrier disruption and brain edema by downregulating the expressions of MMP9, ANG-2 and AQP4. Our results indicate that teriparatide is neuroprotective through multiple mechanisms of action that include promoting angiogenesis, inhibiting oxidative stress and neuroinflammation, protecting blood-brain barrier, and reducing brain edema.

Keywords

Angiogenesis; Blood-brain barrier; Ischemic cerebral infarction; Neuroinflammation; Oxidative stress; Teriparatide.

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