Neuroprotective and Angiogenesis Effects of Levetiracetam Following Ischemic Stroke in Rats
| Autor: | Hairong Zhao, Dafa Shi, Zhendong Ren, Haoran Zhang, Qiu Guo, Yingjiang Gu, Guangwei Yang, Xiang Yao, Wenping Yang, Yanfei Li, Ziyang Yu, Ke Ren |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Angiogenesis levetiracetam Ischemia Morris water navigation task RM1-950 Pharmacology Neuroprotection Brain ischemia 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine.artery medicine ischemic stroke heat shock protein 70 Pharmacology (medical) hypoxia-inducible factor Original Research vascular endothelial growth factor business.industry medicine.disease Vascular endothelial growth factor 030104 developmental biology medicine.anatomical_structure chemistry Cerebral cortex Middle cerebral artery neuroprotection Therapeutics. Pharmacology business 030217 neurology & neurosurgery |
| Zdroj: | Frontiers in Pharmacology, Vol 12 (2021) Frontiers in Pharmacology |
| ISSN: | 1663-9812 |
| DOI: | 10.3389/fphar.2021.638209 |
| Popis: | Objective: The present study explored whether levetiracetam (LEV) could protect against experimental brain ischemia and enhance angiogenesis in rats, and investigated the potential mechanisms in vivo and in vitro.Methods: The middle cerebral artery was occluded for 60 min to induce middle cerebral artery occlusion (MCAO). The Morris water maze was used to measure cognitive ability. The rotation test was used to assess locomotor function. T2-weighted MRI was used to assess infarct volume. The neuronal cells in the cortex area were stained with cresyl purple. The anti-inflammatory effects of LEV on microglia were observed by immunohistochemistry. Enzyme-linked immunosorbent assays (ELISA) were used to measure the production of pro-inflammatory cytokines. Western blotting was used to detect the levels of heat shock protein 70 (HSP70), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1α (HIF-1α) in extracts from the ischemic cortex. Flow cytometry was used to observe the effect of LEV on neuronal cell apoptosis.Results: LEV treatment significantly increased the density of the surviving neurons in the cerebral cortex and reduced the infarct size (17.8 ± 3.3% vs. 12.9 ± 1.4%, p < 0.01) after MCAO. Concurrently, the time required to reach the platform for LEV-treated rats was shorter than that in the saline group on day 11 after MCAO (p < 0.01). LEV treatment prolonged the rotarod retention time on day 14 after MCAO (84.5 ± 6.7 s vs. 59.1 ± 6.2 s on day 14 compared with the saline-treated groups, p < 0.01). It also suppressed the activation of microglia and inhibited TNF-α and Il-1β in the ischemic brain (135.6 ± 5.2 pg/ml vs. 255.3 ± 12.5 pg/ml, 18.5 ± 1.3 pg/ml vs. 38.9 ± 2.3 pg/ml on day 14 compared with the saline-treated groups, p < 0.01). LEV treatment resulted in a significant increase in HIF-1α, VEGF, and HSP70 levels in extracts from the ischemic cerebral cortex. At the same time, LEV reduced neuronal cell cytotoxicity and apoptosis induced by an ischemic stroke (p < 0.01).Conclusion: LEV treatment promoted angiogenesis and functional recovery after cerebral ischemia in rats. These effects seem to be mediated through anti-inflammatory and antiapoptotic activities, as well as inducing the expression of HSP70, VEGF, and HIF-1α. |
| Databáze: | OpenAIRE |
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