The Neuroprotective Effect of Picroside II and Its Best Therapeutic Dose and Time Window in Cerebral Ischemic Injury in Rats


Objective: To study the neuroprotective effect of picrosede II and explore the best therapeutic dose and time window according to orthogonal design in cerebral ischemic injury in rats. Methods: The forebrain ischemia rat models were established by bilateral common carotid artery occlusion (BCCAO) method. The successful models were randomly grouped according to orthogonal experimental design and treated by injecting picroside II intraperitoneally at different ischemic time with different doses. The contents of neuron-specific enolase (NSE), neuroglial marker protein S100B and myelin basic protein (MBP) in serum and brain tissue were determined by enzyme linked immunosorbent assay (ELISA) to evaluate the therapeutic effect of picroside II in cerebral ischemic injury. Results: The best therapeutic time window and dose of picroside II in cerebral ischemic injury may be 1) ischemia 1.5 h with 20 mg/kg and ischemia 1.5 h with 10 mg/kg body weight according to the content of NSE in serum and brain tissue respectively, 2) ischemia 1.5 h with 20 mg/kg according to the content of S100B in both serum and brain tissue, and 3) ischemia 1.5 h with 20 mg/kg and ischemia 1.5 h with 10 mg/kg according to the content of MBP in serum and brain tissue respectively. Conclusion: Based on the principle of the minimization of therapeutic drug dose and maximization of therapeutic time window, the optimal composition of the therapeutic dose and time window of picroside II in treating cerebral ischemic injury should be achieved by injecting picroside II intraperitoneally with 10-20 mg/kg body weight at ischemia 1.5 h in cerebral ischemic injury in rats.

Share and Cite:

L. Zhao, X. Li, Y. Guo, C. Chang and F. Pang, "The Neuroprotective Effect of Picroside II and Its Best Therapeutic Dose and Time Window in Cerebral Ischemic Injury in Rats," Journal of Behavioral and Brain Science, Vol. 3 No. 5, 2013, pp. 385-392. doi: 10.4236/jbbs.2013.35039.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] J. Joseph, F. F. Cruz-Sánchez and J. Carreras, “Enolase Activity and Isoenzyme Distribution in Human Brain Regions and Tumors,” Journal of Neurochemistry, Vol. 66, No. 6, 1996, pp. 2484-2490. doi:10.1046/j.1471-4159.1996.66062484.x
[2] V. Selakovic, R. Raicevic and L. Radenovic, “The Increase of Neuron-Specific Enolase in Cerebrospinal Fluid and Plasma as a Marker of Neuronal Damage in Patients with Acute Brain Infarction,” Journal of Clinical Neuroscience, Vol. 12, No. 5, 2005, pp. 542-547. doi:10.1016/j.jocn.2004.07.019
[3] R. H. Hatfield and R. M. McKernan, “CSF Neuron-Specific Enolase as a Quantitative Marker of Neuronal Damage in a Rat Stroke Model,” Brain Research, Vol. 577, No. 2, 1992, pp. 249-252. doi:10.1016/0006-8993(92)90280-M
[4] L. Y. Jin, Z. Y. Liu, X. W. Yang, Q. L. Sui and Y. L. Guo, “The Expression and Serum Level of NSE and S-100β after Cerebral Ischemia Reperfusion in Rabbits,” Chinese Journal of Rehabilitation Medicine, Vol. 22, No. 11, 2007, pp. 964-967.
[5] T. X. Niu, Z. Y. Shi, J. J. Luo and X. D. Meng, “Determination and Clinical Significance of NSE and S-100β Protein in Hypoxia-Ischemia Brain Injured Rats (in Chinese),” Chinese Journal of Comparative Medicine, Vol. 19, No. 9, 2009, pp. 34-37.
[6] J. Zhen, T. Chen, M. Kong, Z. D. Li, L. Kou, H. W. Liu, et al., “The Influence of Shuxuetong Injection to Serum NSE Levels and Functional Recovery in Patients with Acute Cerebral Infarction,” China Journal of Chinese Maternal Medicine, Vol. 36, No. 18, 2011, pp. 2584-2587.
[7] E. C. Jauch, C. Lindsell, J. Broderick, S. C. Fagan, B. C. Tilley and S. R. Levine, “NINDS rt-PA Stroke Study Group. Association of Serial Biochemical Markers with Acute Ischemic Stroke: The National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Study,” Stroke, Vol. 37, No. 10, 2006, pp. 2508-2513. doi:10.1161/01.STR.0000242290.01174.9e
[8] C. Foerch, M. T. Wunderlich, F. Dvorak, M. Humpich, T. Kahles, M. Goertler, et al., “Elevated Serum S100B Levels Indicate a Higher Risk of Hemorrhagic Transformation after Thrombolytic Therapy in Acute Stroke,” Stroke, Vol. 38, No. 9, 2007, pp. 2491-2495. doi:10.1161/STROKEAHA.106.480111
[9] H. Sienkiewicz-Jarosz, M. Galecka-Wolska, A. Bidziński, D. Turzyńska, A. Sobolewska, B. Lipska, et al., “Predictive Value of Selected Biochemical Markers of Brain Damage for Functional Outcome in Ischaemic Stroke Patients,” Neurologia i Neurochirurgia Polska, Vol. 43, No. 2, 2009, pp. 126-133.
[10] T. Yardan, A. K. Erenler, A. Baydin, K. Aydin and C. Cokluk, “Usefulness of S100B Protein in Neurological Disorders,” Journal of Pakistan Medical Association, Vol. 61, No. 3, 2011, pp. 276-281.
[11] R. L. Büyükuysal, “Protein S100B Release from Rat Brain Slices during and after Ischemia: Comparison with Lactate Dehydrogenase Leakage,” Neurochemistry International, Vol. 47, No. 8, 2005, pp. 580-588. doi:10.1016/j.neuint.2005.06.009
[12] M. üstündag, M. Orak, C. Güloglu, Y. Tamam, M. B. Sayhan and E. Kale, “The Role of Serum Osteoprotegerin and S-100 Protein Levels in Patients with Acute Ischaemic Stroke: Determination of Stroke Subtype, Severity and Mortality,” Journal of International Medical Research, Vol. 39, No. 3, 2011, pp. 780-789. doi:10.1177/147323001103900310
[13] R. Kazmierski, S. Michalak, A. Wencel-Warot and W. L. Nowinski, “Serum Tight-Junction Proteins Predict Hemorrhagic Transformation in Ischemic Stroke Patients,” Neurology, Vol. 79, No. 16, 2012, pp. 1677-1685. doi:10.1212/WNL.0b013e31826e9a83
[14] M. T. Wunderlich, C. W. Wallesch and M. Goertler, “Release of Neurobiochemical Markers of Brain Damage Is Related to the Neurovascular Status on Admission and the Site of Arterial Occlusion in Acute Ischemic Stroke,” Journal of the Neurological Sciences, Vol. 227, No. 1, 2004, pp. 49-53. doi:10.1016/j.jns.2004.08.005
[15] K. J. Lamers, P. Vos, M. M. Verbeek, F. Rosmalen, W. J. van Geel and B. G. van Engelen, “Protein S-100B, Neuron-Specific Enolase (NSE), Myelin Basic Protein (MBP) and Glial Fibrillary Acidic Protein (GFAP) in Cerebrospinal Fluid (CSF) and Blood of Neurological Patients,” Brain Research Bulletin, Vol. 61, No. 3, 2003, pp. 261-264. doi:10.1016/S0361-9230(03)00089-3
[16] M. A. Bedell, N. A. Jenkins and N. G. Copeland, “Good Genes in Bad Neighbourhoods,” Nature Genetics, Vol. 12, No. 3, 1996, pp. 229-232. doi:10.1038/ng0396-229
[17] Y. Z. Chen, Q. Yi, G. Liu, X. Shen, L. H. Xuan and Y. Tian, “Cerebral White Matter Injury and Damage to Myelin Sheath Following Whole-Brain Ischemia,” Brain Research, Vol. 1495, No. 1, 2013, pp. 11-17. doi:10.1016/j.brainres.2012.12.006
[18] Y. L. Guo, X. Y. Xu, Q. Li, Z. Li and F. Du, “Anti-Inflammation Effects of Picroside II in Cerebral Ischemic Injury Rats,” Behavioral Brain Function, Vol. 6, No. 1, 2010, pp. 43-53. doi:10.1186/1744-9081-6-43
[19] Z. Li, Q. Li, W. Shen and Y. L. Guo, “The Interferring Effects of Picroside II on the Expressions of NF-κB and I-κB Following Cerebral Ischemia Reperfusion Injury in Rats,” Chinese Pharmacological Bulletin, Vol. 26, No. 1, 2010, pp. 52-55.
[20] H. T. Pei, X. Su, L. Zhao, H. Y. Li, Y. L. Guo, M. Z. Zhang, et al., “Primary Study for the Therapeutic Dose and Time Window of Picroside II in Treating Cerebral Ischemic Injury in Rats,” International Journal of Molecular Sciences, Vol. 13, No. 3, 2012, pp. 2551-2562.
[21] A. Márquez-Martín, F. Jiménez-Altayó, A. P. Dantas, L. Caracuel, A. M. Planas and E. Vila, “Middle Cerebral Artery Alterations in a Rat Chronic Hypoperfusion Model,” Journal of Applied Physiology, Vol. 112, No. 3, 2012, pp. 511-518. doi:10.1152/japplphysiol.00998.2011
[22] G. B. Uinn, I. G. Reeves and I. N. Day, “Mapping of Antigenic Sites in Human Neuron Specific Enolase by Expression Subcloning,” Clinical Chemistry, Vol. 40, No. 5, 1994, pp. 790-795.
[23] M. T. Wunderlich, H. Lins, M. Skalej, C. W. Wallesch and M. Goertler, “Neuron-Specific Enolase and Tau Pro tein as Neurobiochemical Markers of Neuronal Damage Are Related to Early Clinical Course and Long-Term Outcome in Acute Ischemic Stroke,” Clinical Neurology and Neurosurgery, Vol. 108, No. 6, 2006, pp. 558-563. doi:10.1016/j.clineuro.2005.12.006
[24] M. Murabayashi, M. Minato, Y. Okuhata, M. Makimoto, S. Hosono, N. Masaoka, et al., “Kinetics of Serum S100B in Newborns with Intracranial Lesions,” Pediatrics International, Vol. 50, No. 1, 2008, pp. 17-22. doi:10.1111/j.1442-200X.2007.02506.x
[25] R. Gerlach, G. Demel, H. G. Konig, U. Gross, J. H. Prehn, A. Raabe, et al., “Active Secretion of S100B from Astrocytes during Metabolic Stress,” Neuroscience, Vol. 141, No. 4, 2006, pp. 1697-1701. doi:10.1016/j.neuroscience.2006.05.008
[26] D. T. Laskowitz, S. E. Kasner, J. Saver, K. S. Remmel, E. C. Jauch and BRAIN Study Group, “Clinical Usefulness of a Biomarker-Based Diagnostic Test for Acute Stroke: The Biomarker Rapid Assessment in Ischemic Injury (BRAIN) Study,” Stroke, Vol. 40, No. 1, 2009, pp. 77-85. doi:10.1161/STROKEAHA.108.516377
[27] C. Reali, R. Pillai, F. Saba, S. Cabras, F. Michetti and V. Sogos, “S100B Modulates Growth Factors and Costimulatory Molecules Expression in Cultured Human Astrocytes,” Journal of Neuroimmunology, Vol. 243, No. 1-2, 2012, pp. 95-99. doi:10.1016/j.jneuroim.2011.11.011
[28] T. Mori, J. Tan, G. W. Arendash, N. Koyama, Y. Nojima and T. Town, “Overexpression of Human S100B Exacerbates Brain Damage and Periinfarct Gliosis after Permanent Focal Ischemia,” Stroke, Vol. 39, No. 7, 2008, pp. 2114-2121. doi:10.1161/STROKEAHA.107.503821
[29] R. Brouns, B. De Vil, P. Cras, D. De Surgeloose, P. Marien and P. P. De Deyn, “Neurobiochemical Markers of Brain Damage in Cerebrospinal Fluid of Acute Ischemic Stroke Patients,” Clinical Chemistry, Vol. 56, No. 3, 2010, pp. 451-458. doi:10.1373/clinchem.2009.134122
[30] R. Gregersen, T. Christensen, E. Lehrmann, N. H. Diemer and B. Finsen, “Focal Cerebral Ischemia Induces Increased Myelin Basic Protein and Growth-Associated Protein43 Gene Transcription in Peri-Infarct Areas in the Rat Brain,” Experimental Brain Research, Vol. 138, No. 3, 2001, pp. 384-392. doi:10.1007/s002210100715
[31] T. Strand, C. Alling, B. Karlsson, I. Karlsson and B. Winblad, “Brain and Plasma Proteins in Spinal Fluid as Markers for Brain Damage and Severity of Stroke,” Stroke, Vol. 15, No. 1, 1984, pp. 138-144. doi:10.1161/01.STR.15.1.138

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.