Fluoxetine is one of the most promising drugs for improving clinical outcome in patients with ischemic stroke. This in vivo study investigated the hypothesis that fluoxetine may affect HIF-1α-Netrin/VEGF cascade, angiogenesis and neuroprotection using a rat model of transient middle cerebral artery occlusion (tMCAO). The rats were given fluoxetine or saline after tMCAO for 4 weeks. Then, protein expression of HIF-1α-Netrin/VEGF cascade was examined at 1, 2, 4 weeks after tMCAO. In vivo synchrotron radiation were performed to observe microangiography of ischemic brain after 4 weeks of tMCAO. The infarct size and neurobehavioral test were carried out 1 to 4 weeks after tMCAO. Results revealed that HIF-1α expression was upregulated in fluoxetine-treated group. Similarly, fluoxetine increased protein expression of Netrin and its receptor DCC, VEGF and its receptor VEGFR. Synchrotron radiation angiography revealed more branches in fluoxetine-treated rats. We found no difference of infarct volume between fluoxetine and saline treated rats after 1 week of tMCAO, and ischemia-induced brain atrophy volume in fluoxetine-treated group was attenuated after 4 weeks of tMCAO. Neurological deficits were improved in fluoxetine-treated rats at 3 and 4 weeks after tMCAO. Our results indicated that fluoxetine could upregulate protein expression of HIF-1α-Netrin/VEGF cascade, promote angiogenesis, and improve long-term functional recovery after ischemic stroke.
- Hypoxia-inducible factor-1α
- Middle cerebral artery occlusion
- Vascular endothelial growth factor
ASJC Scopus subject areas
- Developmental Neuroscience