Hepatocyte growth factor improved learning and memory dysfunction of microsphere-embolized rats.
Hepatocyte growth factor (HGF), an organotropic factor for regeneration and protection in various organs, has the ability to attenuate cerebral ischemia-induced cell death. The effect of HGF on learning and memory function after cerebral ischemia, however, remains unknown. We have demonstrated that administration of human recombinant HGF (hrHGF) into the ventricle reduced prolongation of the escape latency in acquisition and retention tests of the water maze task on Days 12-28 after microsphere embolism-induced cerebral ischemia. Treatment with hrHGF also attenuated the decrease in viable area and the density and number of perfused cerebral vessels, particularly those with a diameter smaller than 10 microm, of the ipsilateral hemisphere on Day 28 after the cerebral ischemia. We observed that treatment with hrHGF reduced the number of TUNEL-positive cerebral endothelial cells at the early stage after the ischemia. These results suggest that hrHGF prevents learning and memory dysfunction seen after sustained cerebral ischemia by protecting against injury to the endothelial cells. HGF treatment may be a potent therapeutic strategy for cerebrovascular diseases, including cerebral infarct and vascular dementia.
Date
Ichiro
I
Department of Pharmacology, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 Tokyo, Japan.
Takagi
Norio
N
Takagi
Keiko
K
Kago
Tomoyuki
T
Matsumoto
Kunio
K
Nakamura
Toshikazu
T
Takeo
Satoshi
S
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D007839:Functional Laterality / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D020287:In Situ Nick-End Labeling / Q000379:methods; D020766:Intracranial Embolism / Q000150:complications / Q000188:drug therapy*; D007858:Learning / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology; D008863:Microspheres; D009422:Nervous System Diseases / Q000188:drug therapy / Q000209:etiology; D009460:Neurologic Examination / Q000379:methods; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage; D013194:Staining and Labeling / Q000379:methods; D013997:Time Factors
D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D001973:Bromodeoxyuridine