Ultrasound/microbubble-mediated tetramethylpyrazine for neuroprotection against cerebral ischemia/reperfusion-injured rat brain

The traditional Chinse medicine tetramethylpyrazine (TMP) has shown great promising for neuroprotection against brain injury induced by cerebral ischemia/reperfusion (I/R). In the present work, the neuroprotection effect of TMP combined with ultrasound (US)-activated microbubble (MB) destruction was investigated in a rat middle cerebral artery occlusion (MCAO) model. By using various biochemical and imaging analysis methods (e.g., Evans Blue extravasation, small animal fluorescent imaging, 2,3,5-triphenyltetrazolium chloride staining, histological evaluation, MRI and immunofluorescence staining), the combined neuroprotection effect was comprehensively evaluated with reference to the capability of blood–brain barrier (BBB) opening, the reduction of infarct volume, and the inhibition of proliferation and activation of astrocytes in the peri-infarct area. During all the data analyses, statistical significance was identified as p