Tumor necrosis factor alpha expression produces increased blood-brain barrier permeability following temporary focal cerebral ischemia in mice

Alteration of blood-brain barrier (BBB) function occurs in both permanent a nd temporary cerebral ischemia, Studies in vivo and in vitro have shown tha t turner necrosis factor-alpha (TNF alpha) is involved in changes of BBB pe rmeability. However, the relationship between TNF alpha expression and BBB disruption during reperfusion is unclear, The aim of this study is to find the cell source of TNF alpha and to determine the relationship between TNF alpha expression and BBB disruption following temporary focal cerebral isch emia in mice. Adult CD-I mice received 1 h middle cerebral artery occlusion (MCAO) followed by 2 h, 6 h, 12 h, 24 h, and 38 h of reperfusion. MCAO was achieved using an intraluminal suture technique and reperfusion was perfor med by the suture withdrawal. Neutralizing monoclonal anti-mouse TNF alpha antibody was administrated intraventricularly immediately after reperfusion , TNF alpha expression was determined by double labeling immunohistochemist ry. BBB permeability was determined by albumin immunostaining. TNF alpha im munoreactivity (IR) was observed in the ipsilateral hemisphere from 1 h MCA O with 2 h reperfusion. TNF alpha positive cells included neurons, astrocyt es, and ependymal cells. BBB disruption was detected beginning at 6 h reper fusion but was not present at 2 h of reperfusion. The areas of BBB disrupti on were significantly enlarged at 12 h reperfusion and plateaued at 24 h to 48 h reperfusion. BBB disruptions were significantly attenuated in the ant i-TNF alpha antibody treated mice(p<0.05). Our results demonstrate that TNF alpha IR existed in neurons, astrocytes, and ependymal cells during reperf usion. TNF alpha IR following temporary focal cerebral ischemia precedes in creased BBB permeability. Treatment with TNF alpha. antibody reduces BBB di sruption, suggesting TNF alpha may be an important mediator in altering BBB permeability during reperfusion. (C) 1999 Elsevier Science B.V. All rights reserved.