Abstract: Objective To study the effect of neuregulin 1β(NRG1β) on the morphology and structure of brain tissues after cerebral ischemia and reperfusion injury in rats. Methods A focal cerebral ischemic model was established by inserting a monofilament thread to achieve middle cerebral artery occlusion(MCAO),and the rats were randomly divided into 5 groups:the sham operation group,the model group,the treatment group,the inhibitor group,the inhibitor plus treatment group.The intervention treatment was performed by internal carotid artery injection of 5 μl (2 μg/kg) NRG1β.The regional cerebral blood flow(rCBF) was measured by Laser Doppler flowmeter(LDF).The cerebral infarct volumes were determined by triphenyl tetrazolium chloride(TTC) staining.The morphology of cortical brain tissues was observed by hematoxylin-eosin staining.The expression of pERK5 was evaluated by immunohistochemical assay.The ultrastructure of blood-brain barrier was detected by transmission electron microscope. Results After cerebral ischemia,the rCBF of rats significantly dropped to no more than 30% of the baseline,while after the reperfusion,the rCBF returned to more than 80% of the baseline.In model group,the damage of cortex infarctions,nerve cells and neurons structure was aggravating,and the expression of pERK5 protein compensatorily enhanced after cerebral ischemia reperfusion injury.Compared with the model group,the expression of pERK5 protein further enhanced(P<0.05),the damage of nerve cells alleviated,cerebral infarction volume shrank(P<0.01) in the treatment group.In the inhibitor group,cortex nerve cell seriously damaged,the expression of pERK5 protein significantly decreased,the cerebral infarction volume significantly increased,and the cortex nerve cell was seriously damaged.Compared with the inhibitor group,the expression of pERK5 protein in the inhibitor plus treatment group obviously increased(P<0.01),the nerve cell seriously damaged,the volume of cerebral infarction significantly reduced(P<0.001). Conclusion NRG1β may play a neuroprotective role through activating the ERK5 signaling pathway to improve the morphology and ultrastructure of brain tissue infarction area.