Intraventricular administration of hepatocyte growth factor treats mouse communicating hydrocephalus induced by transforming growth factor beta1.
Communicating hydrocephalus may occur spontaneously in elderly patients or occur as a complication of meningitis or intracranial hemorrhage, typically as a result of fibrosis along the route of cerebrospinal fluid (CSF) flow. Hepatocyte growth factor (HGF) has anti-fibrotic properties and is a promising candidate for the treatment of various fibrotic diseases. Thus, the goal of this study was to examine the effect of exogenous HGF (30 microg of human recombinant (hr) HGF intraventricularly for 7 or 14 days) in a model of hr transforming growth factor beta1-induced communicating hydrocephalus in C57BL/6 mice. HGF treatment resulted in a reduction of ventriculomegaly, as demonstrated by magnetic resonance imaging, and improved spatial memory. Further, ink passage test demonstrated improvement of normalized CSF in flow in mice receiving HGF treatment as opposed to delayed CSF flow in the hydrocephalic mice at baseline. Finally, histological examination in hydrocephalic mice undergoing HGF treatment revealed reduction of collagen fibers in the meninges and normalization of their structures. These results indicate that exogenous HGF may be of utility in the treatment of hydrocephalus in humans.
Tada
Tsuyoshi
T
Department of Neurosurgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan. tadatsu@hsp.md.shinshu-u.ac.jp
Zhan
Hua
H
Tanaka
Yuichiro
Y
Hongo
Kazuhiro
K
Matsumoto
Kunio
K
Nakamura
Toshikazu
T
D000818:Animals; D003094:Collagen / Q000187:drug effects / Q000648:ultrastructure; D004195:Disease Models, Animal; D005355:Fibrosis / Q000139:chemically induced / Q000188:drug therapy; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage*; D006801:Humans; D006849:Hydrocephalus / Q000139:chemically induced / Q000188:drug therapy* / Q000648:ultrastructure; D007276:Injections, Intraventricular; D008279:Magnetic Resonance Imaging; D018782:Maze Learning / Q000187:drug effects; D008578:Meninges / Q000187:drug effects / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017228:Hepatocyte Growth Factor; D003094:Collagen