TY - JOUR
T1 - Extremely low frequency electromagnetic stimulation reduces ischemic stroke volume by improving cerebral collateral blood flow
AU - Kemps, Hannelore
AU - Dessy, Chantal
AU - Dumas, Laurent
AU - Sonveaux, Pierre
AU - Alders, Lotte
AU - Van Broeckhoven, Jana
AU - Font, Lena Perez
AU - Lambrichts, Sara
AU - Foulquier, Sebastien
AU - Hendrix, Sven
AU - Brône, Bert
AU - Lemmens, Robin
AU - Bronckaers, Annelies
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research is supported by the ‘Special Research Funds’ (BOF) of Hasselt University (grants # BOF20TT04 and 18NI06BOF to Annelies Bronckaers and Hannelore Kemps). At UCLouvain, this study was supported by the Fonds National de la Recherche Scientifique (F.R.S.-FNRS, grants # J.0111.17F to Chantal Dessy, and grants # 1.5.141.06 and 1.B181.08 to Pierre Sonveaux). Chantal Dessy and Pierre Sonveaux are Senior Research Associate and Research Director of the F.R.S.-FNRS respectively. Robin Lemmens is a senior clinical investigator of Fonds Wetenschappelijk Onderzoek (FWO) Flanders. Acknowledgements
Funding Information:
The authors would like to send out a word of gratitude to Marc Jans, Evelyne Van Kerckhove, Jeanine Santermans, Thibaut Vazeille, Rachid El Kaddouri, Tim Vangansewinkel, and Laura Ponsaerts for their excellent technical assistance. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research is supported by the ‘Special Research Funds’ (BOF) of Hasselt University (grants # BOF20TT04 and 18NI06BOF to Annelies Bronckaers and Hannelore Kemps). At UCLouvain, this study was supported by the Fonds National de la Recherche Scientifique (F.R.S.-FNRS, grants # J.0111.17F to Chantal Dessy, and grants # 1.5.141.06 and 1.B181.08 to Pierre Sonveaux). Chantal Dessy and Pierre Sonveaux are Senior Research Associate and Research Director of the F.R.S.-FNRS respectively. Robin Lemmens is a senior clinical investigator of Fonds Wetenschappelijk Onderzoek (FWO) Flanders.
Publisher Copyright:
© The Author(s) 2022.
PY - 2022/6
Y1 - 2022/6
N2 - Extremely low frequency electromagnetic stimulation (ELF-EMS) has been considered as a neuroprotective therapy for ischemic stroke based on its capacity to induce nitric oxide (NO) signaling. Here, we examined whether ELF-EMS reduces ischemic stroke volume by stimulating cerebral collateral perfusion. Moreover, the pathway responsible for ELF-EMS-induced NO production was investigated. ELF-EMS diminished infarct growth following experimental stroke in collateral-rich C57BL/6 mice, but not in collateral-scarce BALB/c mice, suggesting that decreased lesion sizes after ELF-EMS results from improved collateral blood flow. In vitro analysis demonstrated that ELF-EMS increased endothelial NO levels by stimulating the Akt-/eNOS pathway. Furthermore, ELF-EMS augmented perfusion in the hind limb of healthy mice, which was mediated by enhanced Akt-/eNOS signaling. In healthy C57BL/6 mouse brains, ELF-EMS treatment increased cerebral blood flow in a NOS-dependent manner, whereas no improvement in cerebrovascular perfusion was observed in collateral-sparse BALB/c mice. In addition, ELF-EMS enhanced cerebral blood flow in both the contra- and ipsilateral hemispheres of C57BL/6 mice subjected to experimental ischemic stroke. In conclusion, we showed that ELF-EMS enhances (cerebro)vascular perfusion by stimulating NO production, indicating that ELF-EMS could be an attractive therapeutic strategy for acute ischemic stroke by improving cerebral collateral blood flow.
AB - Extremely low frequency electromagnetic stimulation (ELF-EMS) has been considered as a neuroprotective therapy for ischemic stroke based on its capacity to induce nitric oxide (NO) signaling. Here, we examined whether ELF-EMS reduces ischemic stroke volume by stimulating cerebral collateral perfusion. Moreover, the pathway responsible for ELF-EMS-induced NO production was investigated. ELF-EMS diminished infarct growth following experimental stroke in collateral-rich C57BL/6 mice, but not in collateral-scarce BALB/c mice, suggesting that decreased lesion sizes after ELF-EMS results from improved collateral blood flow. In vitro analysis demonstrated that ELF-EMS increased endothelial NO levels by stimulating the Akt-/eNOS pathway. Furthermore, ELF-EMS augmented perfusion in the hind limb of healthy mice, which was mediated by enhanced Akt-/eNOS signaling. In healthy C57BL/6 mouse brains, ELF-EMS treatment increased cerebral blood flow in a NOS-dependent manner, whereas no improvement in cerebrovascular perfusion was observed in collateral-sparse BALB/c mice. In addition, ELF-EMS enhanced cerebral blood flow in both the contra- and ipsilateral hemispheres of C57BL/6 mice subjected to experimental ischemic stroke. In conclusion, we showed that ELF-EMS enhances (cerebro)vascular perfusion by stimulating NO production, indicating that ELF-EMS could be an attractive therapeutic strategy for acute ischemic stroke by improving cerebral collateral blood flow.
KW - Akt-
KW - BRAIN-INJURY
KW - GATED CALCIUM-CHANNELS
KW - HIPPOCAMPAL NEUROGENESIS
KW - IN-VITRO
KW - INFARCT SIZE
KW - L-ARGININE
KW - MICE
KW - MICROCIRCULATION
KW - NITRIC-OXIDE SYNTHASE
KW - STATIC MAGNETIC-FIELDS
KW - cerebral collateral blood flow
KW - eNOS pathway
KW - extremely low frequency electromagnetic stimulation
KW - ischemic stroke
KW - nitric oxide
U2 - 10.1177/0271678X221084410
DO - 10.1177/0271678X221084410
M3 - Article
C2 - 35209740
SN - 0271-678X
VL - 42
SP - 979
EP - 996
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
IS - 6
M1 - 0271678X221084410
ER -