TY - JOUR
T1 - Low intensity rTMS has sex-dependent effects on the local response of glia following a penetrating cortical stab injury
AU - Clarke, Darren
AU - Penrose, Marissa A.
AU - Harvey, Alan R.
AU - Rodger, Jennifer
AU - Bates, Kristyn A.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - Repetitive transcranial magnetic stimulation (rTMS), a non-invasive form of brain stimulation, has shown experimental and clinical efficacy in a range of neuromodulatory models, even when delivered at low intensity (i.e. subthreshold for action potential generation). After central nervous system (CNS) injury, studies suggest that reactive astrocytes and microglia can have detrimental but also beneficial effects; thus modulating glial activity, for example through application of rTMS, could potentially be a useful therapeutic tool following neurotrauma. Immunohistochemistry was used to measure the effect of low intensity rTMS (LI-rTMS) on GFAP (astrocyte), IBA1 (microglial), and CS56 (proteoglycan) expression in a unilateral penetrating cortical stab injury model of glial scarring in young adult and aged male and female C57BL6/J mice. Mice received contralateral low frequency, ipsilateral low frequency, ipsilateral high frequency or sham LI-rTMS (4–5 mT intensity), for two weeks following injury. There was no significant difference in the overall volume of tissue containing GFAP positive (+) astrocytes, IBA1+ microglia, or proteoglycan expression, between sham and LI-rTMS-treated mice of all ages and sex. Importantly however, the density of GFAP+ astrocytes and IBA1+ microglia immediately adjacent to the injury was significantly reduced following ipsilateral low and high frequency stimulation in adult and aged females (p ≤ 0.05), but was significantly increased in adult and aged males (p ≤ 0.05). LI-rTMS effects were generally of greater magnitude in aged mice compared to young adult mice. These results suggest that sex differences need to be factored into therapeutic rTMS protocols. In particular, more work analyzing frequency and intensity specific effects, especially in relation to age and sex, is required to determine how rTMS can best be used to modify glial reactivity and phenotype following neurotrauma.
AB - Repetitive transcranial magnetic stimulation (rTMS), a non-invasive form of brain stimulation, has shown experimental and clinical efficacy in a range of neuromodulatory models, even when delivered at low intensity (i.e. subthreshold for action potential generation). After central nervous system (CNS) injury, studies suggest that reactive astrocytes and microglia can have detrimental but also beneficial effects; thus modulating glial activity, for example through application of rTMS, could potentially be a useful therapeutic tool following neurotrauma. Immunohistochemistry was used to measure the effect of low intensity rTMS (LI-rTMS) on GFAP (astrocyte), IBA1 (microglial), and CS56 (proteoglycan) expression in a unilateral penetrating cortical stab injury model of glial scarring in young adult and aged male and female C57BL6/J mice. Mice received contralateral low frequency, ipsilateral low frequency, ipsilateral high frequency or sham LI-rTMS (4–5 mT intensity), for two weeks following injury. There was no significant difference in the overall volume of tissue containing GFAP positive (+) astrocytes, IBA1+ microglia, or proteoglycan expression, between sham and LI-rTMS-treated mice of all ages and sex. Importantly however, the density of GFAP+ astrocytes and IBA1+ microglia immediately adjacent to the injury was significantly reduced following ipsilateral low and high frequency stimulation in adult and aged females (p ≤ 0.05), but was significantly increased in adult and aged males (p ≤ 0.05). LI-rTMS effects were generally of greater magnitude in aged mice compared to young adult mice. These results suggest that sex differences need to be factored into therapeutic rTMS protocols. In particular, more work analyzing frequency and intensity specific effects, especially in relation to age and sex, is required to determine how rTMS can best be used to modify glial reactivity and phenotype following neurotrauma.
KW - Aging
KW - Astrocytes
KW - Central nervous system injury
KW - Microglia
KW - Proteoglycans
KW - Repetitive transcranial magnetic stimulation
KW - Sex differences
UR - http://www.scopus.com/inward/record.url?scp=85020869331&partnerID=8YFLogxK
U2 - 10.1016/j.expneurol.2017.06.019
DO - 10.1016/j.expneurol.2017.06.019
M3 - Article
C2 - 28624361
AN - SCOPUS:85020869331
SN - 0014-4886
VL - 295
SP - 233
EP - 242
JO - Experimental Neurology
JF - Experimental Neurology
ER -