Effects of lipopolysaccharide priming on acute ischemic brain injury

Background and Purpose-Infection has been implicated as a stroke risk facto r. Activation and infiltration of polymorphonuclear neutrophils (PMNs) afte r cerebral ischemia may contribute to ischemic brain injury. This study was conducted to investigate how enhanced postischemic PMN infiltration by lip opolysaccharide (LPS) altered the acute ischemic outcomes. Methods-LPS (0.05 mg/kg SC) or vehicle was given to Long-Evans male rats 24 hours before ischemia. Focal cerebral ischemia was induced by temporary li gation of the right middle cerebral artery and both common carotid arteries for 45 minutes. Animals were killed 6 and 24 hours after reperfusion to de termine the extent of PMN infiltration (myeloperoxidase assay), brain edema (wet-dry weight method), and vascular injury (fluorescein isothiocyanate-c onjugated dextran extravasation). The infarct volumes were measured on the basis of TTC stain 24 hours after ischemia. Results-LPS had little effect on body temperature or peripheral white count but substantially enhanced PMN infiltration into the ischemic right middle cerebral artery cortex on the basis of myeloperoxidase activity (6 hours: control, 0 U/g; LPS, 0.186+/-0.025 U/g; 24 hours: control, 0.185+/-0.025 U/ g; LPS, 0.290+/-0.040 U/g; P<0.001) and morphological studies. The extent o f vascular injury defined by the extravasation of fluorescein isothiocyanat e-conjugated dextran into the ischemic tissue (6 hours: control, 3.11+/-0.4 1 mu L/mg protein; LPS, 0.48+/-0.16 mu L/mg protein; 24 hours: control, 1.7 7+/-0.23 mu L/mg protein; LPS, 0.90+/-0.19 mu L/mg protein; P<0.001) and br ain edema determined by the brain water content (6 hours: control, 811.77+/ -1.63%; LPS, 82.09+/-1.25%; 24 hours: control, 89.40+/-0.43%; LPS, 87.88+/0 .58%; P<0.01) were paradoxically reduced by LPS priming. LPS-primed rats al so had smaller infarct volumes (control, 135+/-5 mm(3); LPS, 108+/-12 mm(3) ; P<0.05). Conclusions-Enhanced postischemic PMN infiltration is anticipated to facili tate ischemic brain injury. Contrary to this expectation, results from the present study suggest that an increase in postischemic PMN infiltration aft er LPS priming was not detrimental. These findings challenge the notion tha t postischemic PMN infiltration is uniformly deleterious.