Leukotriene B4 (
LTB4) has been implicated in
ischemic stroke pathology. We examined the prognostic significance of
LTB4 levels in patients with acute middle cerebral artery (
MCA) infarction and their mechanisms in rat
stroke models. In
ischemic stroke patients with
middle cerebral artery infarction, plasma
LTB4 levels were found to increase rapidly, roughly doubling within 24 h when compared to initial post-
stroke levels. Further analyses indicate that poor functional recovery is associated with early and more sustained increase in
LTB4 rather than the peak levels. Results from studies using a rat
embolic stroke model showed increased
5-lipoxygenase (5-LOX) expression in the ipsilateral infarcted cortex compared with
sham control or respective contralateral regions at 24 h post-
stroke with a concomitant increase in
LTB4 levels. In addition, neutrophil influx was also observed in the infarcted cortex. Double immunostaining indicated that neutrophils express 5-LOX and
leukotriene A4 hydrolase (LTA4H), highlighting the pivotal contributions of neutrophils as a source of
LTB4. Importantly, rise in plasma
LTB4 levels corresponded with an increase in
LTB4 amount in the infarcted cortex, thereby supporting the use of plasma as a surrogate for brain
LTB4 levels. Pre-
stroke LTB4 loading increased
brain infarct volume in tMCAO rats. Conversely, administration of the 5-LOX-activating
protein (FLAP) inhibitor
BAY-X1005 or B-
leukotriene receptor (BLTR) antagonist
LY255283 decreased the
infarct volume by a similar extent. To conclude, targeted interruption of the
LTB4 pathway might be a viable treatment strategy for
acute ischemic stroke.