Browsing by Author "Ferreira, Susana Maria Alves"
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- Impact of High Frequency repetitive Magnetic Stimulation on Astrocytes Subjected to IschemiaPublication . Ferreira, Susana Maria Alves; Baltazar, Graça Maria FernandesIschemic stroke (IS) is caused by the reduction or blockage of blood flow to the brain and is the third most common cause of death in Portugal. Due to its ability to improve the most frequent clinical sequelae left by brain ischemia, high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has been considered a promising therapeutic strategy for IS. The observed improvements have been associated with changes in neurons and their synaptic liaisons. However, the hypothesis that this technique modulates astrocytes, potentiating their neuroprotective capabilities, was also raised. With the present work, we aim to clarify which mechanisms triggered by highfrequency repetitive magnetic stimulation (HF-rMS) in astrocytes contribute to its neuroprotective effects. Neuron-glia and astrocyte cortical cultures subject to oxygen and glucose deprivation were used as an in vitro model of ischemia. Neuroprotection promoted by HF-rMS was evaluated through the analysis of markers of neuronal activity and morphometric analysis of neurons. The levels of growth factors in the astrocyteconditioned medium (CM) were assessed through a Growth Factor Array and glialderived neurotrophic factor (GDNF) expression was analyzed by RT-PCR and Western Blot. Our results show that neurons injured by ischemia can be rescued through the modulation of astrocytes by HF-rMS. This modulation helps to maintain the number and length of neurites and increases the number of neurons expressing c-Fos. Quantification of glutamate transporters EAAT1 and EAAT2 in astrocyte extracts showed that EAAT2 levels were not affected by HF-rMS, however, EAAT1 levels were increased in cultures subjected to OGD and HF-rMS, suggesting that HF-rMS neuroprotection may involve a reduction of excitotoxicity. Furthermore, analysis of the astrocyte CM showed that HFrMS stimulated the release of several trophic factors by astrocytes, namely GDNF. Neutralization of GDNF present in the CM impeded the recovery of neurite number and length induced by HF-rMS and blocked the increase of c-Fos+ neurons, indicating that this neurotrophic factor plays a crucial role in the neuronal recovery induced by HF-rMS. Our results show that modulation of astrocytes by HF-rMS effectively rescues neurons injured by ischemia by decreasing excitotoxicity and promoting neuroprotection through the release of GDNF by the astrocytes. This suggests that by targeting astrocytes, HF-rMS can be used to promote neuroprotection in other brain lesions.