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.

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.