Tetramethylpyrazine nitrone, a multifunctional neuroprotective agent for ischemic stroke therapy
| Autor: | Michael K. W. Siu, Henry C. H. Law, Gaoxiao Zhang, Eiketsu Sho, Samuel S. W. Szeto, Pei Yu, Simon Ming-Yuen Lee, Yuqiang Wang, Quan Quan, Guohui Li, Ivan K. Chu, Yewei Sun, Zaijun Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Brain Infarction Male Ischemia Nerve Tissue Proteins Pharmacology Blood–brain barrier Neuroprotection Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Medicine Tetramethylpyrazine Animals cardiovascular diseases Stroke Schiff Bases Multidisciplinary medicine.diagnostic_test business.industry Cerebral infarction Therapeutic effect Magnetic resonance imaging medicine.disease Disease Models Animal Macaca fascicularis 030104 developmental biology medicine.anatomical_structure Neuroprotective Agents chemistry Blood-Brain Barrier Pyrazines business 030217 neurology & neurosurgery Biomarkers |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep37148 |
| Popis: | TBN, a novel tetramethylpyrazine derivative armed with a powerful free radical-scavenging nitrone moiety, has been reported to reduce cerebral infarction in rats through multi-functional mechanisms of action. Here we study the therapeutic effects of TBN on non-human primate model of stroke. Thirty male Cynomolgus macaques were subjected to stroke with 4 hours ischemia and then reperfusion. TBN were injected intravenously at 3 or 6 hours after the onset of ischemia. Cerebral infarction was examined by magnetic resonance imaging at 1 and 4 weeks post ischemia. Neurological severity scores were evaluated during 4 weeks observation. At the end of experiment, protein markers associated with the stroke injury and TBN treatment were screened by quantitative proteomics. We found that TBN readily penetrated the blood brain barrier and reached effective therapeutic concentration after intravenous administration. It significantly reduced brain infarction and modestly preserved the neurological function of stroke-affected arm. TBN suppressed over-expression of neuroinflammatory marker vimentin and decreased the numbers of GFAP-positive cells, while reversed down-regulation of myelination-associated protein 2′, 3′-cyclic-nucleotide 3′-phosphodiesterase and increased the numbers of NeuN-positive cells in the ipsilateral peri-infarct area. TBN may serve as a promising new clinical candidate for the treatment of ischemic stroke. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|