Minocycline inhibits 5-lipoxygenase expression and accelerates functional recovery in chronic phase of focal cerebral ischemia in rats

LS Chu, SH Fang, Y Zhou, YJ Yin, WY Chen, JH Li… - Life sciences, 2010 - Elsevier
LS Chu, SH Fang, Y Zhou, YJ Yin, WY Chen, JH Li, J Sun, ML Wang, WP Zhang, EQ Wei
Life sciences, 2010Elsevier
AIMS: We previously reported that minocycline attenuates acute brain injury and
inflammation after focal cerebral ischemia, and this is partly mediated by inhibition of 5-
lipoxygenase (5-LOX) expression. Here, we determined the protective effect of minocycline
on chronic ischemic brain injury and its relation with the inhibition of 5-LOX expression after
focal cerebral ischemia. MAIN METHODS: Focal cerebral ischemia was induced by 90min of
middle cerebral artery occlusion followed by reperfusion for 36days. Minocycline (45mg/kg) …
AIMS
We previously reported that minocycline attenuates acute brain injury and inflammation after focal cerebral ischemia, and this is partly mediated by inhibition of 5-lipoxygenase (5-LOX) expression. Here, we determined the protective effect of minocycline on chronic ischemic brain injury and its relation with the inhibition of 5-LOX expression after focal cerebral ischemia.
MAIN METHODS
Focal cerebral ischemia was induced by 90min of middle cerebral artery occlusion followed by reperfusion for 36days. Minocycline (45mg/kg) was administered intraperitoneally 2h and 12h after ischemia and then every 12h for 5days. Sensorimotor function was evaluated 1–28days after ischemia and cognitive function was determined 30–35days after ischemia. Thereafter, infarct volume, neuron density, astrogliosis, and 5-LOX expression in the brain were determined.
KEY FINDINGS
Minocycline accelerated the recovery of sensorimotor and cognitive functions, attenuated the loss of neuron density, and inhibited astrogliosis in the boundary zone around the ischemic core, but did not affect infarct volume. Minocycline significantly inhibited the increased 5-LOX expression in the proliferated astrocytes in the boundary zone, and in the macrophages/microglia in the ischemic core.
SIGNIFICANCE
Minocycline accelerates functional recovery in the chronic phase of focal cerebral ischemia, which may be partly associated with the reduction of 5-LOX expression.
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