title: Granulocyte macrophage colony-stimulating factor treatment results in recovery of motor function after white matter damage in mice.
abstract: Clinical stroke usually results from a cerebral ischaemic event, and is frequently a debilitating condition with limited treatment options. A significant proportion of clinical strokes result from specific damage to the subcortical white matter (SWM), but currently there are few animal models available to investigate the pathogenesis and potential therapeutic strategies to promote recovery. Granulocyte macrophage colony-stimulating factor (GM-CSF) is a cytokine that has been previously shown to promote neuroprotective effects after brain damage; however, the mechanisms mediating this effect are not known. Here, it is reported that GM-CSF treatment results in dramatic functional improvement in a white matter model of stroke in mice. SWM stroke was induced in mice by unilateral injections of the vasoconstrictor, endothelin-1 (ET-1). The results reveal that ET-1-induced stroke impairs skilled motor function on the single pellet-reaching task and results in forelimb asymmetry, in adult mice. Treatment with GM-CSF, after stroke, restores motor function and abolishes forelimb asymmetry. The results also indicate that GM-CSF promotes its effects by activating mammalian target of rapamycin signalling mechanisms in the brain following stroke injury. Additionally, a significant increase in GM-CSF receptor expression was found in the ipsilateral hemisphere of the ET-1-injected brain. Taken together, the present study highlights the use of an under-utilized mouse model of stroke (using ET-1) and suggests that GM-CSF treatment can attenuate ET-1-induced functional deficits.
authors.affiliation: Neuroscience Department, Carleton University, 1125 Colonel By Drive, Ottawa, ON, Canada.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Theoret
authors.affiliation: Neuroscience Department, Carleton University, 1125 Colonel By Drive, Ottawa, ON, Canada.
authors.forename: Nafisa M
authors.initials: NM
authors.lastname: Jadavji
authors.affiliation: Neuroscience Department, Carleton University, 1125 Colonel By Drive, Ottawa, ON, Canada.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Neuroscience Department, Carleton University, 1125 Colonel By Drive, Ottawa, ON, Canada.
authors.forename: Patrice D
authors.initials: PD
authors.lastname: Smith
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000139:chemically induced / Q000150:complications*; D003337:Corpus Callosum / Q000187:drug effects* / Q000293:injuries / Q000473:pathology*; D004195:Disease Models, Animal; D019332:Endothelin-1; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects*; D066191:Sensorimotor Cortex / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D066127:White Matter / Q000187:drug effects* / Q000293:injuries / Q000473:pathology*
chemical_list: D019332:Endothelin-1; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases
keywords: endothelin-1; forepaw placement; functional recovery; mammalian target of rapamycin; single pellet-reaching task; white matter stroke model