Decoy administration of NF-kappaB into the subarachnoid space for cerebral angiopathy.
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 KB (NF-kappaB) decoy oligo-DNA after SAH; since NF-kappaB is closely related to inflammation. In the rabbit angiopathy model after SAH, 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-kappaB was also performed in order to evaluate the activity of NF-kappaB. We describe a new concept for treating cerebral angiopathy after SAH and for successfully inhibiting cerebral vasospasm and morphological changes in vessel walls in a rabbit model. In this treatment, we used synthetic double-strand oligo-DNA with a high affinity for transcription factor NF-kappaB, and cationic liposome complex administered through the cerebrospinal fluid.
Ono
S
S
Department of Neurological Surgery, Okayama Medical School, Okayama University, Japan.
Date
I
I
Onoda
K
K
Shiota
T
T
Ohmoto
T
T
Ninomiya
Y
Y
Asari
S
S
Morishita
R
R
D000818:Animals; D004195:Disease Models, Animal; D004337:Drug Carriers; D008081:Liposomes; D008297:Male; D016328:NF-kappa B / Q000235:genetics* / Q000276:immunology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013346:Subarachnoid Space; D014158:Transcription, Genetic
D004337:Drug Carriers; D008081:Liposomes; D016328:NF-kappa B; D016376:Oligonucleotides, Antisense