title: Low intensity repetitive transcranial magnetic stimulation does not induce cell survival or regeneration in a mouse optic nerve crush model.
abstract: Low intensity repetitive Transcranial Magnetic Stimulation (LI-rTMS), a non-invasive form of brain stimulation, has been shown to induce structural and functional brain plasticity, including short distance axonal sprouting. However, the potential for LI-rTMS to promote axonal regeneration following neurotrauma has not been investigated. This study examined the effect of LI-rTMS on retinal ganglion cell (RGC) survival, axon regeneration and levels of BDNF in an optic nerve crush neurotrauma model. Adult C57Bl/6J mice received a unilateral intraorbital optic nerve crush. Mice received 10 minutes of sham (handling control without stimulation) (n=6) or LI-rTMS (n = 8) daily stimulation for 14 days to the operated eye. Immunohistochemistry was used to assess RGC survival (β-3 Tubulin) and axon regeneration across the injury (GAP43). Additionally, BDNF expression was quantified in a separate cohort by ELISA in the retina and optic nerve of injured (optic nerve crush) (sham n = 5, LI-rTMS n = 5) and non-injured mice (sham n = 5, LI-rTMS n = 5) that received daily stimulation as above for 7 days. Following 14 days of LI-rTMS there was no significant difference in mean RGC survival between sham and treated animals (p>0.05). Also, neither sham nor LI-rTMS animals showed GAP43 positive labelling in the optic nerve, indicating that regeneration did not occur. At 1 week, there was no significant difference in BDNF levels in the retina or optic nerves between sham and LI-rTMS in injured or non-injured mice (p>0.05). Although LI-rTMS has been shown to induce structural and molecular plasticity in the visual system and cerebellum, our results suggest LI-rTMS does not induce neuroprotection or regeneration following a complete optic nerve crush. These results help define the therapeutic capacity and limitations of LI-rTMS in the treatment of neurotrauma.
authors.affiliation: Department of Experimental and Regenerative Neurosciences, School of Animal Biology, The University of Western Australia, Perth, WA, Australia.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Tang
authors.affiliation: Department of Experimental and Regenerative Neurosciences, School of Animal Biology, The University of Western Australia, Perth, WA, Australia.
authors.forename: Kalina
authors.initials: K
authors.lastname: Makowiecki
authors.affiliation: Department of Experimental and Regenerative Neurosciences, School of Animal Biology, The University of Western Australia, Perth, WA, Australia.
authors.forename: Carole
authors.initials: C
authors.lastname: Bartlett
authors.affiliation: Department of Experimental and Regenerative Neurosciences, School of Animal Biology, The University of Western Australia, Perth, WA, Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rodger
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002470:Cell Survival; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D008810:Mice, Inbred C57BL; D009409:Nerve Crush; D009416:Nerve Regeneration; D020221:Optic Nerve Injuries / Q000473:pathology* / Q000503:physiopathology*; D012160:Retina / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000473:pathology; D050781:Transcranial Magnetic Stimulation
chemical_list: D019208:Brain-Derived Neurotrophic Factor