Heavy water inhibiting the expression of transforming growth factor-beta1 and the development of kaolin-induced hydrocephalus in mice.
OBJECTIVE
The authors investigated the effects of heavy water (D2O) on intrameningeal fibrosis and on the expression of cytokine production in mice with kaolin-induced hydrocephalus.


METHODS
Mice in which kaolin was injected into the cisterna magna were divided into two groups: 1) Group H, which had free access to H2O as tap water; and 2) Group D, which had free access to 30% D2O as tap water before and after kaolin injection. A distilled water-injected group, which had free access to H2O as tap water was designated the sham-operated group. The authors examined the effects of D2O within 28 days after injection on the development of hydrocephalus and intrameningeal fibrosis, as well as on the expression levels of several inflammatory and fibrogenic cytokines: transforming growth factor-beta1 (TGFbeta1), fibroblast growth factor-2 (FGF2), platelet-derived growth factor (PDGF)-BB, and interleukin (IL)-6. The cerebral ventricles were less expanded, and intrameningeal fibrosis was milder in Group D than in Group H. The proliferation of fibroblasts was assessed by applying the bromodeoxyuridine labeling index, which was lower in Group D than in Group H. Expression of TGFbeta1 in the macrophages, choroid plexus, and meninges was inhibited in Group D but not in Group H. The serum level of total TGFbeta1 was significantly lower in Group D than in Group H on Day 14, whereas the levels of FGF2, PDGF-BB, and IL-6 did not differ significantly among the groups.


CONCLUSIONS
Administration of D2O prevented the development of kaolin-induced hydrocephalus in mice and inhibited intrameningeal fibrosis and upregulation of TGFbeta1.
Hatta
Junko
J
Department of Developmental Biology, Faculty of Medicine, Shimane University, Izumo, Japan. jhatta@med.shimane-u.ac.jp
Hatta
Toshihisa
T
Moritake
Kouzo
K
Otani
Hiroki
H
D000818:Animals; D000077214:Becaplermin; D001921:Brain / Q000473:pathology; D002552:Cerebral Ventricles / Q000473:pathology; D017666:Deuterium Oxide / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D005355:Fibrosis; D006849:Hydrocephalus / Q000139:chemically induced / Q000473:pathology*; D007276:Injections, Intraventricular; D015850:Interleukin-6 / Q000032:analysis; D007616:Kaolin; D008297:Male; D008578:Meninges / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D010982:Platelet-Derived Growth Factor / Q000032:analysis; D020574:Proto-Oncogene Proteins c-sis; D013223:Statistics as Topic; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000037:antagonists & inhibitors*; D053773:Transforming Growth Factor beta1
D015850:Interleukin-6; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin; D007616:Kaolin; D017666:Deuterium Oxide