BACKGROUND AND PURPOSE: Infection has been implicated as a stroke risk factor. Activation and infiltration of polymorphonuclear neutrophils (PMNs) after cerebral ischemia may contribute to ischemic brain injury. This study was conducted to investigate how enhanced postischemic PMN infiltration by lipopolysaccharide (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 ligation of the right middle cerebral artery and both common carotid arteries for 45 minutes. Animals were killed 6 and 24 hours after reperfusion to determine the extent of PMN infiltration (myeloperoxidase assay), brain edema (wet-dry weight method), and vascular injury (fluorescein isothiocyanate-conjugated 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 of vascular injury defined by the extravasation of fluorescein isothiocyanate-conjugated dextran into the ischemic tissue (6 hours: control, 3.11+/-0.41 microliter/mg protein; LPS, 0.48+/-0.16 microliter/mg protein; 24 hours: control, 1.77+/-0.23 microliter/mg protein; LPS, 0. 90+/-0.19 microliter/mg protein; P<0.001) and brain edema determined by the brain water content (6 hours: control, 84.77+/-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 also 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 facilitate ischemic brain injury. Contrary to this expectation, results from the present study suggest that an increase in postischemic PMN infiltration after LPS priming was not detrimental. These findings challenge the notion that postischemic PMN infiltration is uniformly deleterious.
BACKGROUND AND PURPOSE: Infection has been implicated as a stroke risk factor. Activation and infiltration of polymorphonuclear neutrophils (PMNs) after cerebral ischemia may contribute to ischemic brain injury. This study was conducted to investigate how enhanced postischemic PMN infiltration by lipopolysaccharide (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 ligation of the right middle cerebral artery and both common carotid arteries for 45 minutes. Animals were killed 6 and 24 hours after reperfusion to determine the extent of PMN infiltration (myeloperoxidase assay), brain edema (wet-dry weight method), and vascular injury (fluorescein isothiocyanate-conjugated 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 of vascular injury defined by the extravasation of fluorescein isothiocyanate-conjugated dextran into the ischemic tissue (6 hours: control, 3.11+/-0.41 microliter/mg protein; LPS, 0.48+/-0.16 microliter/mg protein; 24 hours: control, 1.77+/-0.23 microliter/mg protein; LPS, 0. 90+/-0.19 microliter/mg protein; P<0.001) and brain edema determined by the brain water content (6 hours: control, 84.77+/-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 also 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 facilitate ischemic brain injury. Contrary to this expectation, results from the present study suggest that an increase in postischemic PMN infiltration after LPS priming was not detrimental. These findings challenge the notion that postischemic PMN infiltration is uniformly deleterious.