Concurrent use of granulocyte-colony stimulating factor with repetitive transcranial magnetic stimulation did not enhance recovery of function in the early subacute stroke in rats

Abstract

We investigated the additive effect of repetitive transcranial magnetic stimulation (rTMS) combined with granulocyte-colony stimulating factor (G-CSF) on functional outcome in the early subacute phase of stroke. Seven-week-old male rats were subjected to permanent middle cerebral artery occlusion (MCAo) and were divided into four groups: normal saline administration with sham rTMS (group 1, n = 15), G-CSF administration with sham rTMS (group 2, n = 15), G-CSF with 1 Hz rTMS (group 3, n = 14), and G-CSF with 20 Hz rTMS (group 4, n = 15). Animals received G-CSF or saline for 5 days from the day of MCAo and were concurrently treated with 20-min rTMS on their lesioned hemisphere for 2 weeks. Neurological functional score was worse in group 4 compared to that in group 2 on day 15. In Western blots conducted on day 25, phosphorylation of endothelial nitric oxide synthase was markedly lower in groups 2, 3, and 4 than that in group 1 in the ischemic border zone. PECAM-1 expression at ischemic core was lower in groups 4 than in group 2. Caspase-3 expression was markedly higher in groups 4 than in group 1, 2, 3 at ischemic core. Iba1 expression was higher in groups 4 than in group 1, 2 at ischemic core. G-CSF combined with rTMS administered in the early subacute phase of ischemic stroke may exert a hazardous effect on functional recovery, possibly due to impaired angiogenic mechanism, decreased cell survival, and increased inflammation.

Repetitive Transcranial Magnetic Stimulation to the Unilateral Hemisphere of Rat Brain

“…2. Maintain propofol sedation at an infusion rate of 500 -700 µg/(kg•min) throughout the experiment, as in a previous study 16 . Supplement oxygen at 0.8 L/min via a nose cone.…”

Noninvasive Brain Stimulation to Enhance Functional Recovery After Stroke: Studies in Animal Models

“…Since the first publication of a TMS study in rats in 1990, there has been an exponential increase in published animal TMS studies, including preclinical studies in animal models of disease. 23,24 Experiments involving repetitive TMS in animal models of Alzheimer's disease, 25 depression, 26 epilepsy, 27 Huntington's disease, 28 Parkinson's disease, 29 and stroke [30][31][32][33][34][35][36][37][38][39][40][41] have already provided substantial insights into the therapeutic potential of TMS.…”

“…An in-depth literature search on PubMed, using combinations of keywords (eg, noninvasive brain stimulation, transcranial magnetic stimulation, rTMS, cerebral/stroke/ ischemia/infarct, disease/animal model, animal, rodent, rat, mice/mouse, gerbil, large animals/nonhuman primate), for animal models of stroke involving treatment with rTMS, revealed 12 scientific articles published between 2003 and October 2017. [30][31][32][33][34][35][36][37][38][39][40][41] These articles (summarized in Table 1) applied rTMS after experimental stroke to assess (1) effects on ischemic tolerance, 30 (2) underlying therapeutic mechanisms, [30][31][32][33][34][35]39,40 (3) the additive effect of TMS when combined with other therapies, [36][37][38] and (4) the effect of rTMS on gene expression. 41 These studies applied TMS using coils of different shapes and sizes.…”

Repetitive transcranial magnetic stimulation improves neurological function after cerebral ischemia in rats by increasing CREB-regulated TrkB via activation of cAMP/PKA and Ca2+/CaMKIV signaling pathways

“…rTMS is a non-invasive brain stimulation which is acceptable to most patients. Its ability to regulate and maintain cerebral cortex excitability until stimulation is terminated to be of great clinical significance [7]. In a previous study, rTMS of human-derived neuron-like cells elevated intracellular cAMP levels and promoted cAMP-response element binding protein (CREB) phosphorylation [8].…”