Decoy administration of NF-κB into the subarachnoid space for cerebral angiopathy

被引:74
作者
Ono, S
Date, I
Onoda, K
Shiota, T
Ohmoto, T
Ninomiya, Y
Asari, S
Morishita, R
机构
[1] Okayama Univ, Sch Med, Dept Neurol Surg, Okayama 700, Japan
[2] Okayama Univ, Sch Med, Dept Mol Biol & Biochem, Okayama 700, Japan
[3] Okayama Univ, Sch Hlth Sci, Dept Nursing, Okayama 700, Japan
[4] Osaka Univ, Sch Med, Dept Geriatr Med, Osaka 553, Japan
关键词
D O I
10.1089/hum.1998.9.7-1003
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Subarachnoid hemorrhage (SAH), encephalitis, meningitis, and autoimmune diseases sometimes lead to cerebral angiopathy, characterized specifically by narrowing of vessels, morphological changes in the structure of vessel walls, and a concomitant decrease in cerebral blood flow. Many patients also develop delayed ischemic neurological deficits. Thus, preventing vascular reactions is of paramount importance in treating SAH. Although cerebral vasospasm has some relationship with the inflammatory reaction of major cerebral vessels against the autologous blood, and many trials have attempted to prevent angiopathy after SAH, an effective treatment has not yet been established, The purpose of this article is to evaluate the preventive effect of nuclear factor kappa B (NF-kappa B) decoy oligo-DNA after SAH; since NF-kappa B is closely related to inflammation. In the rabbit angiopathy model after SAB, we evaluated the effectiveness of the decoy oligo-DNA using the angiographic (digital subtraction angiography) and histological (hematoxylin-eosin and Masson's trichrome staining) methods. Moreover, a gel-shift assay for NF-kappa B was also performed in order to evaluate the activity of NF-kappa B, We describe a new concept for treating cerebral angiopathy after SAH and for successfully inhibiting cerebral vasospasm and morphological changes in vessel malls in a rabbit model. In this treatment, we used synthetic double-strand oligo-DNA with a high affinity for transcription factor NF-kappa B, and cationic liposome complex administered through the cerebrospinal fluid.
引用
收藏
页码:1003 / 1011
页数:9
相关论文
共 31 条
[1]   EFFECT OF INTRACAROTID NITRIC-OXIDE ON PRIMATE CEREBRAL VASOSPASM AFTER SUBARACHNOID HEMORRHAGE [J].
AFSHAR, JKB ;
PLUTA, RM ;
BOOCK, RJ ;
THOMPSON, BG ;
OLDFIELD, EH .
JOURNAL OF NEUROSURGERY, 1995, 83 (01) :118-122
[2]   THE INDUCIBLE TRANSCRIPTION ACTIVATOR NF-KAPPA-B - REGULATION BY DISTINCT PROTEIN SUBUNITS [J].
BAEUERLE, PA .
BIOCHIMICA ET BIOPHYSICA ACTA, 1991, 1072 (01) :63-80
[3]   An essential role for NF-kappa B in preventing TNF-alpha-induced cell death [J].
Beg, AA ;
Baltimore, D .
SCIENCE, 1996, 274 (5288) :782-784
[4]   Stimulatory effect of ouabain on VCAM-1 and iNOS expression in murine endothelial cells: Involvement of NF-kappa B [J].
Bereta, J ;
Cohen, MC ;
Bereta, M .
FEBS LETTERS, 1995, 377 (01) :21-25
[5]   REGULATION OF GENE-EXPRESSION WITH DOUBLE-STRANDED PHOSPHOROTHIOATE OLIGONUCLEOTIDES [J].
BIELINSKA, A ;
SHIVDASANI, RA ;
ZHANG, LQ ;
NABEL, GJ .
SCIENCE, 1990, 250 (4983) :997-1000
[6]   Global ischemia activates nuclear factor-kappa B in forebrain neurons of rats [J].
Clemens, JA ;
Stephenson, DT ;
Smalstig, EB ;
Dixon, EP ;
Little, SP .
STROKE, 1997, 28 (05) :1073-1080
[7]   ARTERIAL-WALL CHANGES IN CEREBRAL VASOSPASM [J].
FINDLAY, JM ;
WEIR, BKA ;
KANAMARU, K ;
ESPINOSA, F .
NEUROSURGERY, 1989, 25 (05) :736-746
[8]   PROSPECTIVE, RANDOMIZED, DOUBLE-BLIND TRIAL OF BQ-123 AND BOSENTAN FOR PREVENTION OF VASOSPASM FOLLOWING SUBARACHNOID HEMORRHAGE IN MONKEYS [J].
HINO, A ;
WEIR, BKA ;
MACDONALD, RL ;
THISTED, RA ;
KIM, CJ ;
JOHNS, LM .
JOURNAL OF NEUROSURGERY, 1995, 83 (03) :503-509
[9]   Prevention of cerebrovasospasm following subarachnoid hemorrhage in rabbits by the platelet-activating factor antagonist, E5880 [J].
Hirashima, Y ;
Endo, S ;
Kato, R ;
Takaku, A .
JOURNAL OF NEUROSURGERY, 1996, 84 (05) :826-830
[10]  
HORIUCHI M, 1991, J BIOL CHEM, V266, P16247