Granulocyte colony-stimulating factor induces sensorimotor recovery in intracerebral hemorrhage.
Granulocyte colony-stimulating factor (G-CSF) has been used in the treatment of neutropenia in hematologic disorders. The neuroprotective and anti-inflammatory effects of G-CSF were reported in various neurological disease models. In this study, we examined whether G-CSF induces functional recovery after intracerebral hemorrhage (ICH). ICH was induced using collagenase injection in adult rats. Either G-CSF (50 microg/kg, i.p.) or saline was given from 2 h after ICH and every 24 h for 3 days. 72 h after ICH induction, the rats were sacrificed for histological analysis and measurement of brain edema. Behavioral tests were performed before and 1, 7, 14, 21, 28, and 35 days after ICH. We also measured the blood-brain barrier (BBB) permeability using Evans blue dye injection method. G-CSF-treated rats recovered better on rotarod and limb placing tests, starting from 14 days throughout 5 weeks after ICH. The brain water content and BBB permeability of G-CSF-treated group decreased in the lesioned hemispheres compared with those of ICH-only group. In G-CSF-treated group, the number of TUNEL+, myeloperoxidase+, and OX42+ cells was smaller than that of ICH-only group in the periphery of hematoma. These findings suggest that G-CSF induces long-term sensorimotor recovery after ICH with reduction of brain edema, inflammation, and perihematomal cell death.
Park
Hee-Kwon
HK
Department of Neurology, Stroke and Neural Stem Cell Laboratory, Clinical Research Institute, Seoul National University Hospital, 28, Yongon-Dong, Chongro-Gu, Seoul, 110-744, South Korea.
Chu
Kon
K
Lee
Soon-Tae
ST
Jung
Keun-Hwa
KH
Kim
Eun-Hee
EH
Lee
Kyung-Bok
KB
Song
Young-Mok
YM
Jeong
Sang-Wuk
SW
Kim
Manho
M
Roh
Jae-Kyu
JK
D000818:Animals; D001284:Atrophy / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D002543:Cerebral Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D017364:Collagenases; D004195:Disease Models, Animal; D004660:Encephalitis / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D005070:Evans Blue; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009069:Movement Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D009410:Nerve Degeneration / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D012678:Sensation Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D016896:Treatment Outcome
D015415:Biomarkers; D018696:Neuroprotective Agents; D016179:Granulocyte Colony-Stimulating Factor; D005070:Evans Blue; D017364:Collagenases