A Novel Ligustrazine Derivative T-VA Prevents Neurotoxicity in Differentiated PC12 Cells and Protects the Brain against Ischemia Injury in MCAO Rats
Abstract
:1. Introduction
2. Results
2.1. Cell Viability and (Hematoxylin-Eosin) HE Stains
2.2. The Expression of NF-κB/p65
2.3. The Expression of COX-2
2.4. Acute Toxic Test in Vivo
2.5. Behavioral Evaluation
2.5.1. T-VA Reduced the Neurological Deficit Score
2.5.2. Beam Walking Test
2.5.3. Bar-Grasping Test
Groups | Dose (mg/kg) | Neurologic Deficit Score | Beam-Walking Test Score | Grasping (g) | |||
---|---|---|---|---|---|---|---|
Ischemia for 3 Days | Ischemia for 7 Days | Ischemia for 3 Days | Ischemia for 7 Days | Ischemia for 3 Days | Ischemia for 7 Days | ||
Sham | – | 0 ± 0 ** | 0 ± 0 ** | 6 ± 0 ** | 6 ± 0 ** | 442.65 ± 62.84 ** | 531.44 ± 64.30 ** |
Model | – | 2.14 ± 0.51 | 1.81 ± 0.56 | 1.47 ± 0.84 | 1.92 ± 2.02 | 317.01 ± 53.81 | 285.58 ± 80.02 |
NMDP | 30 | 1.35 ± 0.39 * | 1.11 ± 0.48 * | 2.71 ± 1.49 ** | 3.50 ± 1.71 * | 409.08 ± 65.13 ** | 393.08 ± 59.61 * |
T-VA | 60 | 1.46 ± 0.41 | 1.26 ± 0.35 * | 3.6 ± 1.76 ** | 3.83 ± 1.70 * | 395.50 ± 16.88 ** | 468.81 ± 78.14 ** |
T-VA | 120 | 1.57 ± 0.37 | 1.34 ± 0.44 | 2.88 ± 1.62 ** | 3.20 ± 1.66 | 386.57 ± 42.35 ** | 421.68 ± 59.87 ** |
TMP | 37 | 1.63 ± 0.4 | 1.45 ± 0.48 | 2.86 ± 1.79 * | 2.40 ± 2.32 | 415.19 ± 26.81 ** | 434.22 ± 50.23 ** |
2.6. Effect of T-VA on Histological Alterations
2.7. Effect of T-VA on VEGF in MCAO Rats
2.8. Detection of Superoxide Dismutase (SOD) Activity and Ca2+–Mg2+ATP Enzyme Activity of Ischemic Brain Tissue
Groups | Dose (mg/kg) | SOD (U/mg Protein) | Ca2+–Mg2+ ATP Enzyme (μmolPi/(mg Protein/h)) |
---|---|---|---|
Sham | – | 61.85 ± 12.53 ** | 3.66 ± 1.29 * |
Model | – | 40.28 ± 7.51 | 5.32 ± 2.61 |
NMDP | 30 | 79.85 ± 36.57 ** | 13.25 ± 5.73 ** |
T-VA | 60 | 75.29 ± 30.08 ** | 8.91 ± 4.05 * |
T-VA | 120 | 85.03 ± 28.03 ** | 10.07 ± 5.15 * |
TMP | 37 | 61.58 ± 16.23 ** | 9.13 ± 4.11 * |
2.9. Statistical Analysis
3. Discussion
4. Experimental Section
4.1. General
4.2. Cell Viability Assay and HE Staining
4.3. The Expression of NF-κB/p65 and COX-2
4.4. Acute Toxicity
4.5. Animal Models for Transient Focal Cerebral Ischemia
4.6. Behavioral Evaluation
4.6.1. Neurological Deficit Score
4.6.2. Beam Walking Test
4.6.3. Bar-Grasping Test
4.7. Pharmacological Analysis: Brain Tissue Preparation for Nissl Stains
4.8. VEGF Expression in Rats with MCAO
4.9. Detection of SOD Activity and Ca2+–Mg2+ATP Enzyme Activity of Ischemic Brain Tissue
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Li, G.; Tian, Y.; Zhang, Y.; Hong, Y.; Hao, Y.; Chen, C.; Wang, P.; Lei, H. A Novel Ligustrazine Derivative T-VA Prevents Neurotoxicity in Differentiated PC12 Cells and Protects the Brain against Ischemia Injury in MCAO Rats. Int. J. Mol. Sci. 2015, 16, 21759-21774. https://doi.org/10.3390/ijms160921759
Li G, Tian Y, Zhang Y, Hong Y, Hao Y, Chen C, Wang P, Lei H. A Novel Ligustrazine Derivative T-VA Prevents Neurotoxicity in Differentiated PC12 Cells and Protects the Brain against Ischemia Injury in MCAO Rats. International Journal of Molecular Sciences. 2015; 16(9):21759-21774. https://doi.org/10.3390/ijms160921759
Chicago/Turabian StyleLi, Guoliang, Yufei Tian, Yuzhong Zhang, Ying Hong, Yingzhi Hao, Chunxiao Chen, Penglong Wang, and Haimin Lei. 2015. "A Novel Ligustrazine Derivative T-VA Prevents Neurotoxicity in Differentiated PC12 Cells and Protects the Brain against Ischemia Injury in MCAO Rats" International Journal of Molecular Sciences 16, no. 9: 21759-21774. https://doi.org/10.3390/ijms160921759