Fibroblast growth factor-18 reduced infarct volumes and behavioral deficits after transient occlusion of the middle cerebral artery in rats.
OBJECTIVE
Fibroblast growth factor 18 (FGF18) is expressed in rodent brain and is a trophic factor for neuron-derived cells in culture. The purpose of the present study was to evaluate whether FGF18 was neuroprotective in a rat model of cerebral ischemia and to compare the results with those obtained with FGF2.


METHODS
Cerebral ischemia was produced in rats by a transient 2-hour occlusion of the middle cerebral artery (MCAo) with an intraluminal filament followed by 22-hour reperfusion. Starting 15 minutes after MCAo, FGF18 or FGF2 was administered by a 3-hour intravenous infusion. Infarct volumes and behavioral deficits were measured 24 hours after MCAo.


RESULTS
Infusion of FGF18 produced dose-dependent reductions in infarct volumes and improvements in tests of reference and working memory, motor ability, and exploratory behavior. FGF18 was more efficacious than FGF2 on virtually all measures examined. The reductions in infarct volume and behavioral deficit were associated with FGF-mediated increases in regional cerebral blood flow.


CONCLUSIONS
These results demonstrate that FGF18 is an effective neuroprotective agent in a rat model of transient MCAo.
Ellsworth
Jeff L
JL
ZymoGenetics, Inc, 1201 Eastlake Ave E, Seattle, Wash 98102, USA. jefe@zgi.com
Garcia
Richard
R
Yu
Jin
J
Kindy
Mark S
MS
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001783:Blood Flow Velocity / Q000187:drug effects; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage; D005346:Fibroblast Growth Factors / Q000008:administration & dosage*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007262:Infusions, Intravenous; D002546:Ischemic Attack, Transient / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
D018696:Neuroprotective Agents; C113569:fibroblast growth factor 18; D016222:Fibroblast Growth Factor 2; D005346:Fibroblast Growth Factors