Neuroprotective Effects Of Tanshinone â…¡A On Permanent Focal Cerebral Ischemia In Mice

Stroke is one of the most frequent causes of disability and death worldwide, but the treatment of it was short of. Danshen is a commonly used traditional Chinese medicine for the treatment of cardiovascular and Cerebrovascular diseases. Tanshinone IIA (TSA), as a key compound of Danshen, has been proved to protect the brain from transient ischemia injury. But there was no report of its effects on brain injury after permanent focal cerebral ischemia and little is known about its mechanism. The objective of this study was to evaluate whether Tanshinone IIA (TSA) was neuroprotective in permanent focal cerebral ischemia and to determine the possible mechanisms of its neuroprotection.This experiment contains two parts. The first part was to measure the neuroprotection of TSA and the second part was to find the possible mechanisms of its function. Method: Animals were randomly divided into 5 groups: sham, vehicle, TSA 20mg/kg, TSA 10mg/kg and TSA 5mg/kg. In addition, there was a positive control group in the first part of the experiment. Mice were subjected to permanent middle cerebral artery occlusion for 24h. The neuroprotection of TSA was investigated with respect to neurological deficit scores and infarct volume. Biochemical analysis for malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in serum, and nitric oxide (NO) content and the inducible nitric oxide synthase (iNOS) activity in brain tissue were performed at 24h after ischemia. Immunohistochemistry was used to measure the expression of iNOS. In vitro, 5 groups were used: control, model, TSA 8μM, TSA 4μM and TSA 2μM. The effects of TSA were tested in the cultured astrocytes exposed to hydrogen dioxide (H₂O₂). Result: TSA (10 and 20 mg/kg, i.p.) significantly reduced the infarct volume and TSA 20mg/kg improve neurological deficit 8h after ischemia remarkably. TSA (10 and 20 mg/kg, i.p.) significantly increased the activity of SOD after 24h of ischemia and decreased the MDA level in serum, and suppressed the NO content in brain tissue. All of the three treatment groups remarkably reduced the activity of iNOS in brain, and the expression of iNOS was also inhibited. In vitro, the translocation of NF-κB was inhibited by TSA and the survival rate of astrocytes was markedly increased as well as the NO production was decreased.Conclusion: These results illustrated that TSA protected brain from ischemic injury by suppressing the oxidative stress and the radical-mediated inflammatory insult.