DECOY ADMINISTRATION OF NF-KAPPA-B INTO THE SUBARACHNOID SPACE FOR CEREBRAL ANGIOPATHY

Subarachnoid hemorrhage (SAH), encephalitis, meningitis, and autoimmun e diseases sometimes lead to cerebral angiopathy, characterized specif ically by narrowing of vessels, morphological changes in the structure of vessel walls, and a concomitant decrease in cerebral blood flow. M any 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 infla mmatory reaction of major cerebral vessels against the autologous bloo d, 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 r elated to inflammation. In the rabbit angiopathy model after SAB, we e valuated the effectiveness of the decoy oligo-DNA using the angiograph ic (digital subtraction angiography) and histological (hematoxylin-eos in and Masson's trichrome staining) methods. Moreover, a gel-shift ass ay 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 angiop athy after SAH and for successfully inhibiting cerebral vasospasm and morphological changes in vessel malls in a rabbit model. In this treat ment, we used synthetic double-strand oligo-DNA with a high affinity f or transcription factor NF-kappa B, and cationic liposome complex admi nistered through the cerebrospinal fluid.