IB4, a monoclonal antibody against the CD18 leukocyte adhesion protein, reduces intracranial pressure following thromboembolic stroke in the rabbit.
Neutrophil activation and accumulation as a consequence of cerebral ischemia-reperfusion has been suggested to exacerbate tissue injury. The current study is designed to examine the effect of IB4, a monoclonal antibody directed against the neutrophil adhesion protein, CD18, in a rabbit model of thromboembolic stroke. New Zealand rabbits (3-3.5 kg n=8 each group), were given an autologous clot embolus, delivered to the anterior circulation of the brain via the internal carotid artery. Immediately following thromboembolism, the mean arterial pressure in all animals was reduced to 30 mmHg by controlled exsanguination for a period of 45 min. All animals were mechanically ventilated and following parameters were monitored hourly: arterial blood gases, intracranial pressure, regional cerebral blood flow, hematocrit, and core temperature. Rabbits were given either IB4 (1 mg kg(-1)), or vehicle (1 percent albumin, IV) 30 min following the thromboembolic event. The mean arterial pressure of all animals was restored to the baseline value of 50-60 mmHg for the remainder of the 4-h experiment. Following the thromboembolic event, the intracranial pressure rose in both groups, although this was significantly less in the IB4-treated group, with the final values being 195.9 +/- 38.3 vs. 135.5 +/- 26.0 percent of baseline (mean +/- SEM, p < 0.05). However, regional cerebral blood flow and infarct size (TTC staining) were virtually identical in both groups. It is concluded that blockade of the neutrophil adhesion protein, CD18, may contribute to a reduction in the intracranial pressure following cerebral ischemia and reperfusion, providing further evidence that activated neutrophils may contribute to cerebral edema.
Bednar
M M
MM
Vermont Center for Vascular Research, University of Vermont, Burlington 05405-0068, USA.
Wright
S D
SD
Raymond-Russell
S J
SJ
Kohut
J J
JJ
Gross
C E
CE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology*; D018821:CD18 Antigens / Q000276:immunology*; D002448:Cell Adhesion; D002560:Cerebrovascular Circulation / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000503:physiopathology*; D005260:Female; D002542:Intracranial Embolism and Thrombosis / Q000503:physiopathology*; D007427:Intracranial Pressure / Q000187:drug effects*; D007962:Leukocytes / Q000502:physiology; D008297:Male; D011817:Rabbits; D013997:Time Factors
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens