title: 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.
authors.affiliation: Department of Rehabilitation Medicine, Chungnam National University Hospital, Daejeon, 301-721, Republic of Korea.
authors.forename: Jaewon
authors.initials: J
authors.lastname: Beom
authors.forename: Won
authors.initials: W
authors.lastname: Kim
authors.forename: Tai Ryoon
authors.initials: TR
authors.lastname: Han
authors.forename: Kwan-Sik
authors.initials: KS
authors.lastname: Seo
authors.forename: Byung-Mo
authors.initials: BM
authors.lastname: Oh
mesh_terms: D000818:Animals; D001703:Biophysics; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D008297:Male; D009460:Neurologic Examination; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D018709:Statistics, Nonparametric; D020521:Stroke / Q000473:pathology / Q000628:therapy*; D013997:Time Factors; D050781:Transcranial Magnetic Stimulation / Q000379:methods*
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D052250:Nitric Oxide Synthase Type III; D051058:Oncogene Protein v-akt