title: The effects of tetrahydrobiopterin on intracerebral hemorrhage-induced brain injury in mice.
abstract: Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthase (NOS) and is presently used clinically to treat forms of phenylketonuria. BH4 has been reported to restrain superoxide generation of NOS and chemically reduce superoxide. However, there has been no report concerning the effects of BH4 in intracerebral hemorrhage (ICH). In the present study, we investigated the neuroprotective effect of BH4 against ICH-induced brain injury in a mouse model.A total of 26 male CD1 mice (31-39 g) were divided into sham, ICH-vehicle, and ICH-treated with BH4 groups (n = 8 in each group). ICH was induced by collagenase injection into the right basal ganglia. BH4 (20 mg/kg) was administrated intraperitoneally at 1 h after ICH. The effect of BH4 was measured by neurological score and brain water content at 24 h after ICH.Our data demonstrates that ICH caused significant neurological deficit that is associated with brain edema. Treatment with BH4 did not reduce brain edema and neurological deficits at 24 h after ICH in mice. Further study is required to investigate the long-term effect of BH4 in ICH-induced brain injury.
authors.affiliation: Department of Physiology and Pharmacology, Loma Linda University Medical Center, Loma Linda, CA 92354, USA.
authors.forename: Reiko
authors.initials: R
authors.lastname: Tsuchiyama
authors.forename: Takumi
authors.initials: T
authors.lastname: Sozen
authors.forename: Elena
authors.initials: E
authors.lastname: Titova
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
authors.forename: Jiping
authors.initials: J
authors.lastname: Tang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology; D001930:Brain Injuries / Q000188:drug therapy* / Q000209:etiology*; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000150:complications*; D017364:Collagenases / Q000009:adverse effects; D004195:Disease Models, Animal; D007839:Functional Laterality; D008297:Male; D051379:Mice; D009460:Neurologic Examination; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011597:Psychomotor Performance / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents; D001708:Biopterins; D017364:Collagenases; C003402:sapropterin