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77 Background: The transcription factor, NF-κB,  plays a pivotal role in the inflammatory cascade. Transcription factor  decoys (TFDs)are phosphorothioated oligonucleotides that bind activated  NF-κB and prevent the transcription of inflammatory genes. We have  shown that TFDs can be delivered into brain endothelial cellsin  vitro using mannitol and that an NF-κB TFD can block the  upregulation of the ICAM-1 gene(Stroke 2000;31:1179–86).  Objectives:1.) To determine if intra-arterial mannitol can deliver TFDs  into endothelial cellsin vivo 2.) To determine if an  NF-κB decoy delivered with intra-arterial mannitol reduces cerebral  infarct size.Methods: The temporary middle cerebral artery  suture occlusion (2 hrs) model was performed in male Wistar rats.  Intra-arterial mannitol was used to transfect phosphorothiaoted  oligonucleotide decoys into brain endothelial cells. Decoy was detected  using fluoroscein-tagged TFDs with immunohistochemical amplification.  Infarct size was measured at 48 hours by TTC staining. The NF-κB  decoy was a 38 mer with 3 NF-κB binding sites. A scrambled decoy (38  mer with same base composition but random sequence) was used as  control.Results: With intra-arterial mannitol, the TFD was  visualized in cerebral vessels in the injected hemisphere only.  Double-labeling studies using a lectin (Griffonia simplicifolia) to  label endothelial cells indicated that much of this labeling was in  endothelial cells. Without mannitol or with a cationic liposome  preparation, no decoy could be visualized. Animals treated with NF-κB  decoy (at reperfusion) had significantly smaller infarcts than control  animals (saline treatment)p=.036 Fishers PLSD [Control (N=6) 33.8  ± 1.1 (mean + SE) % of hemisphere vs NF-κB decoy with mannitol  (N=4) 25.9 ± 3.4; mannitol alone (N=3)33.8 ± 4.3 ,  scrambled decoy with mannitol (N=3)32.3 ±  2.0]Conclusions: Intra-arterial mannitol permits the  delivery of phosphorothioated oligonuclotides into brain endothelial  cellsin vivo . An NF-κB decoy delivered with  intra-arterial mannitol may decrease infarct size. This approach may  have clinical application as an adjunctive treatment to intra-arterial  tPA

Reducing tissue injury in acute ischemic stroke by targeting NF-κB with transcription factor decoys.