The paper aims to optimize
the therapeutic dose and time window of picroside II by orthogonal test in cerebral
ischemic injury in rats. The forebrain ischemia models were established by
bilateral common carotid artery occlusion (BCCAO) methods. The successful
models were randomly divided into sixteen groups according to orthogonal
and treated by injecting picroside IIintraperitonenally at different
ischemic time with different dose. The
neuron-specific enolase (NSE), neuroglial marker protein S100B and myelin basic
protein (MBP) in serum were determined by enzyme linked immunosorbent assay to
evaluate the therapeutic effect of picroside II in cerebral ischemic injury. The
results indicated that best therapeutic time window and dose of picroside II in cerebral ischemic injury were
with 20mg/kgbody weight according to the
concentrations of NSE, S100B and MBP in serum. It is
concluded that according to the principle of lowest therapeutic dose with
longest time window, the optimized therapeutic dose and time window are injecting picroside II intraperitonenally with 20mg/kg body weight at ischemia 1.5h in cerebral ischemic injury in rats.
Cite this paper
H. Huang, L. Sun, L. Wang, L. Fang, L. Zhao and Y. Li, "To Optimize the Therapeutic Dose and Time Window of Picroside II in Cerebral Ischemic Injury in Rats by Orthogonal Test," Neuroscience and Medicine, Vol. 4 No. 3, 2013, pp. 166-171. doi: 10.4236/nm.2013.43027.
 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.
 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.
 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. 557, No. 2, 1992, pp. 249-252.
 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 Comprehensive Medical, Vol. 19, 2009, pp. 34-37.
 E. C. Jauch, C. Lindsell, J. Broderick, S. C. Fagan, B. C. Tilley, S. R. Levine and 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, 2006, pp. 2508-2513. doi:10.1161/01.STR.0000242290.01174.9e
 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, 2011, pp. 276-281.
 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,” Severity and Mortality, Vol. 39, 2011, pp. 780-789.
 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, 2012, pp. 1677-1685.
 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
 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
 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, 2013, pp. 11-17.
 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, 2010, pp. 52-55.
 Z. Li, Q. Li, Y. L. Guo, L. H. Qin and L. J. Luan, “Intervention Effects of PicrosideⅡ in Cerebral Ischemic Injury Rats,” Acta Anat Sinica, Vol. 41, 2010, pp. 9-12.
 Y. L. Guo, X. Y. Xu, Q. Li, Z. Li and F. Du, “Anti-Inflammation Effects of PicrosideⅡ in Cerebral Ischemic Injury Rats,” Behavioral Brain Function, Vol. 6, 2010, pp. 43-53.
 H. T. Pei, X. Su, L. Zhao, H. Y. Li, Y. L. Guo, M. Z. Zhang and H. Xin, “Primary Study for the Therapeutic Dose and Time Window of PicrosideⅡ in Treating Cerebral Ischemic Injury in Rats,” International Journal of Molecular Sciences, Vol. 13, 2012, pp. 2551-2562.
 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, 2012, pp. 511-518. doi:10.1152/japplphysiol.00998.2011
 R. Gerlach, G. Demel, H. G. Konig, U. Gross, J. H. Prehn, A. Raabe, V. Seifert and D. Kogel, “Active Secretion of S100B from Astrocytes during Metabolic Stress,” Neuroscience, Vol. 141, No. 4, 2006, pp. 1697-1701.
 D. T. Laskowitz, S. E. Kasner, J. Saver, K. S. Remmel and E. C. Jauch, “Clinical Usefulness of a BiomarkerBased Diagnostic Test for Acute Stroke: The Biomarker Rapid Assessment in Ischemic Injury (BRAIN) Study,” Stroke, Vol. 40, 2009, pp. 77-85.
 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
 M. T. Wunderlich, H. Lins, M. Skalej, C. W. Wallesch and M. Goertler, “Neuron-Specific Enolase and Tau Protein 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.
 R. Gregersen, T. Christensen, E. Lehrmann, N. H. Diemer and B. Finsen, “Focal Cerebral Ischemia Induces Increased Myelin Basic Protein and Growth-Associated Protein-43 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
 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, 1984, pp. 138-144. doi:10.1161/01.STR.15.1.138