Neurochemical Research

, Volume 38, Issue 3, pp 530–537 | Cite as

Propofol Increases Expression of Basic Fibroblast Growth Factor After Transient Cerebral Ischemia in Rats

  • Xiao-Chun Zhao
  • Li-Min Zhang
  • Dong-Yi Tong
  • Ping An
  • Chao Jiang
  • Ping Zhao
  • Wei-Min Chen
  • Jian Wang
Original Paper


Anesthetics such as propofol can provide neuroprotective effects against cerebral ischemia. However, the underlying mechanism of this beneficial effect is not clear. Therefore, we subjected male Sprague–Dawley rats to 2 h of middle cerebral artery occlusion and investigated how post-ischemic administration of propofol affected neurologic outcome and the expression of basic fibroblast growth factor (bFGF). After 2 h of ischemia, just before reperfusion, the animals were randomly assigned to receive either propofol (20 mg kg−1 h−1) or vehicle (10 % intralipid, 2 ml kg−1 h−1) intravenously for 4 h. Neurologic scores, infarct volume, and brain water content were measured at different time points after reperfusion. mRNA level of bFGF was measured by real-time PCR, and the protein expression level of bFGF was analyzed by immunohistochemistry and Western blot. At 6, 24, 72 h, and 7 days of reperfusion, infarct volume was significantly reduced in the propofol-treated group compared to that in the vehicle-treated group (all P < 0.05). Propofol post-treatment also attenuated brain water content at 24 and 72 h and reduced neurologic deficit score at 72 h and 7 days of reperfusion (all P < 0.05). Additionally, in the peri-infarct area, bFGF mRNA and protein expression were elevated at 6, 24, and 72 h of reperfusion compared to that in the vehicle-treated group (all P < 0.05). These results show that post-ischemic administration of propofol provides neural protection from cerebral ischemia–reperfusion injury. This protection may be related to an early increase in the expression of bFGF.


Brain Basic fibroblast growth factor Ischemia–reperfusion Propofol 



This work was supported by NSFC (81000824, 81101402, 81171782), and NIH (K01AG031926, R01AT007317, R01NS078026). We thank Claire Levine for assistance with this manuscript.


  1. 1.
    Kawaguchi M, Furuya H, Patel PM (2005) Neuroprotective effects of anesthetic agents. J Anesth 19:150–156PubMedCrossRefGoogle Scholar
  2. 2.
    Harman F, Hasturk AE, Yaman M, Arca T, Kilinc K, Sargon MF, Kaptanoglu E (2012) Neuroprotective effects of propofol, thiopental, etomidate, and midazolam in fetal rat brain in ischemia-reperfusion model. Childs Nerv Syst 28:1055–1062PubMedCrossRefGoogle Scholar
  3. 3.
    Schwartz-Bloom RD, Miller KA, Evenson DA, Crain BJ, Nadler JV (2000) Benzodiazepines protect hippocampal neurons from degeneration after transient cerebral ischemia: an ultrastructural study. Neuroscience 98:471–484PubMedCrossRefGoogle Scholar
  4. 4.
    Cole DJ, Cross LM, Drummond JC, Patel PM, Jacobsen WK (2001) Thiopentone and methohexital, but not pentobarbitone, reduce early focal cerebral ischemic injury in rats. Can J Anaesth 48:807–814PubMedCrossRefGoogle Scholar
  5. 5.
    Li H, Tan J, Zou Z, Huang CG, Shi XY (2011) Propofol post-conditioning protects against cardiomyocyte apoptosis in hypoxia/reoxygenation injury by suppressing nuclear factor-kappa B translocation via extracellular signal-regulated kinase mitogen-activated protein kinase pathway. Eur J Anaesthesiol 28:525–534PubMedCrossRefGoogle Scholar
  6. 6.
    Ariyama J, Shimada H, Aono M, Tsuchida H, Hirai KI (2000) Propofol improves recovery from paraquat acute toxicity in vitro and in vivo. Intensive Care Med 26:981–987PubMedCrossRefGoogle Scholar
  7. 7.
    Hans P, Bonhomme V, Collette J, Albert A, Moonen G (1994) Propofol protects cultured rat hippocampal neurons against N-methyl-D-aspartate receptor-mediated glutamate toxicity. J Neurosurg Anesthesiol 6:249–253PubMedGoogle Scholar
  8. 8.
    Schlunzen L, Juul N, Hansen KV, Cold GE (2012) Regional cerebral blood flow and glucose metabolism during propofol anaesthesia in healthy subjects studied with positron emission tomography. Acta Anaesthesiol Scand 56:248–255PubMedCrossRefGoogle Scholar
  9. 9.
    Jin YH, Zhang Z, Mendelowitz D, Andresen MC (2009) Presynaptic actions of propofol enhance inhibitory synaptic transmission in isolated solitary tract nucleus neurons. Brain Res 1286:75–83PubMedCrossRefGoogle Scholar
  10. 10.
    Herring BE, McMillan K, Pike CM, Marks J, Fox AP, Xie Z (2011) Etomidate and propofol inhibit the neurotransmitter release machinery at different sites. J Physiol 589:1103–1115Google Scholar
  11. 11.
    Watanabe T, Okuda Y, Nonoguchi N et al (2004) Postischemic intraventricular administration of FGF-2 expressing adenoviral vectors improves neurologic outcome and reduces infarct volume after transient focal cerebral ischemia in rats. J Cereb Blood Flow Metab 24:1205–1213PubMedCrossRefGoogle Scholar
  12. 12.
    Kiprianova I, Schindowski K, von Bohlen und Halbach O, Krause S, Dono R, Schwaninger M, Unsicker K (2004) Enlarged infarct volume and loss of BDNF mRNA induction following brain ischemia in mice lacking FGF-2. Exp Neurol 189:252–260PubMedCrossRefGoogle Scholar
  13. 13.
    Chen J, Li Y, Katakowski M, Chen X, Wang L, Lu D, Lu M, Gautam SC, Chopp M (2003) Intravenous bone marrow stromal cell therapy reduces apoptosis and promotes endogenous cell proliferation after stroke in female rat. J Neurosci Res 73:778–786PubMedCrossRefGoogle Scholar
  14. 14.
    Lasarzik I, Winkelheide U, Stallmann S, Orth C, Schneider A, Tresch A, Werner C, Engelhard K (2009) Assessment of postischemic neurogenesis in rats with cerebral ischemia and propofol anesthesia. Anesthesiology 110:529–537PubMedCrossRefGoogle Scholar
  15. 15.
    Jiang X, Gao L, Zhang Y, Wang G, Liu Y, Yan C, Sun H (2011) A comparison of the effects of ketamine, chloral hydrate and pentobarbital sodium anesthesia on isolated rat hearts and cardiomyocytes. J Cardiovasc Med (Hagerstown) 12:732–735CrossRefGoogle Scholar
  16. 16.
    Li W, Zheng B, Xu H, Deng Y, Wang S, Wang X, Su D (2012) Isoflurane prevents neurocognitive dysfunction after cardiopulmonary bypass in rats. J Cardiothorac Vasc Anesth. doi: 10.1053/j.jvca.2012.09.005..
  17. 17.
    Longa EZ, Weinstein PR, Carlson S, Cummins R (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke J Cerebral circul 20:84–91CrossRefGoogle Scholar
  18. 18.
    Wang H, Luo M, Li C, Wang G (2011) Propofol post-conditioning induced long-term neuroprotection and reduced internalization of AMPAR GluR2 subunit in a rat model of focal cerebral ischemia/reperfusion. J Neurochem 119:210–219PubMedCrossRefGoogle Scholar
  19. 19.
    Chen J, Sanberg PR, Li Y, Wang L, Lu M, Willing AE, Sanchez-Ramos J, Chopp M (2001) Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats. Stroke J Cerebral Circul 32:2682–2688CrossRefGoogle Scholar
  20. 20.
    Chen J, Li Y, Wang L, Zhang Z, Lu D, Lu M, Chopp M (2001) Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke 32:1005–1011PubMedCrossRefGoogle Scholar
  21. 21.
    Shimakura A, Kamanaka Y, Ikeda Y, Kondo K, Suzuki Y, Umemura K (2000) Neutrophil elastase inhibition reduces cerebral ischemic damage in the middle cerebral artery occlusion. Brain Res 858:55–60PubMedCrossRefGoogle Scholar
  22. 22.
    Ping A, Chun ZX, Xue XY (2005) Bradykinin preconditioning induces protective effects against focal cerebral ischemia in rats. Brain Res 1059:105–112PubMedCrossRefGoogle Scholar
  23. 23.
    Wang J, Tsirka SE (2005) Neuroprotection by inhibition of matrix metalloproteinases in a mouse model of intracerebral haemorrhage. Brain 128:1622–1633PubMedCrossRefGoogle Scholar
  24. 24.
    Van Hemelrijck J, Fitch W, Mattheussen M, Van Aken H, Plets C, Lauwers T (1990) Effect of propofol on cerebral circulation and autoregulation in the baboon. Anesth Analg 71:49–54PubMedGoogle Scholar
  25. 25.
    Watts AD, Eliasziw M, Gelb AW (1998) Propofol and hyperventilation for the treatment of increased intracranial pressure in rabbits. Anesth Analg 87:564–568PubMedGoogle Scholar
  26. 26.
    Dam M, Ori C, Pizzolato G, Ricchieri GL, Pellegrini A, Giron GP, Battistin L (1990) The effects of propofol anesthesia on local cerebral glucose utilization in the rat. Anesthesiology 73:499–505PubMedCrossRefGoogle Scholar
  27. 27.
    Wilson JX, Gelb AW (2002) Free radicals, antioxidants, and neurologic injury: possible relationship to cerebral protection by anesthetics. J Neurosurg Anesthesiol 14:66–79PubMedCrossRefGoogle Scholar
  28. 28.
    Ito H, Watanabe Y, Isshiki A, Uchino H (1999) Neuroprotective properties of propofol and midazolam, but not pentobarbital, on neuronal damage induced by forebrain ischemia, based on the GABAA receptors. Acta Anaesthesiol Scand 43:153–162PubMedCrossRefGoogle Scholar
  29. 29.
    Engelhard K, Werner C, Hoffman WE, Matthes B, Blobner M, Kochs E (2003) The effect of sevoflurane and propofol on cerebral neurotransmitter concentrations during cerebral ischemia in rats. Anesth Analg 97:1155–1161 table of contentsPubMedCrossRefGoogle Scholar
  30. 30.
    Engelhard K, Werner C, Eberspacher E, Pape M, Blobner M, Hutzler P, Kochs E (2004) Sevoflurane and propofol influence the expression of apoptosis-regulating proteins after cerebral ischaemia and reperfusion in rats. Eur J Anaesthesiol 21:530–537PubMedGoogle Scholar
  31. 31.
    Jin-qiao S, Bin S, Wen-hao Z, Yi Y (2009) Basic fibroblast growth factor stimulates the proliferation and differentiation of neural stem cells in neonatal rats after ischemic brain injury. Brain Dev 31:331–340PubMedCrossRefGoogle Scholar
  32. 32.
    Lenhard T, Schober A, Suter-Crazzolara C, Unsicker K (2002) Fibroblast growth factor-2 requires glial-cell-line-derived neurotrophic factor for exerting its neuroprotective actions on glutamate-lesioned hippocampal neurons. Mol Cell Neurosci 20:181–197PubMedCrossRefGoogle Scholar
  33. 33.
    Tanaka R, Miyasaka Y, Yada K, Ohwada T, Kameya T (1995) Basic fibroblast growth factor increases regional cerebral blood flow and reduces infarct size after experimental ischemia in a rat model. Stroke 26:2154–2158 discussion 2158–2159PubMedCrossRefGoogle Scholar
  34. 34.
    Speliotes EK, Caday CG, Do T, Weise J, Kowall NW, Finklestein SP (1996) Increased expression of basic fibroblast growth factor (bFGF) following focal cerebral infarction in the rat. Brain Res Mol Brain Res 39:31–42PubMedCrossRefGoogle Scholar
  35. 35.
    Lin TN, Te J, Lee M, Sun GY, Hsu CY (1997) Induction of basic fibroblast growth factor (bFGF) expression following focal cerebral ischemia. Brain Res Mol Brain Res 49:255–265PubMedCrossRefGoogle Scholar
  36. 36.
    Wei OY, Huang YL, Da CD, Cheng JS (2000) Alteration of basic fibroblast growth factor expression in rat during cerebral ischemia. Acta Pharmacol Sin 21:296–300PubMedGoogle Scholar
  37. 37.
    Fujiwara K, Date I, Shingo T, Yoshida H, Kobayashi K, Takeuchi A, Yano A, Tamiya T, Ohmoto T (2003) Reduction of infarct volume and apoptosis by grafting of encapsulated basic fibroblast growth factor-secreting cells in a model of middle cerebral artery occlusion in rats. J Neurosurg 99:1053–1062PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Xiao-Chun Zhao
    • 1
  • Li-Min Zhang
    • 1
  • Dong-Yi Tong
    • 1
  • Ping An
    • 2
  • Chao Jiang
    • 3
  • Ping Zhao
    • 1
  • Wei-Min Chen
    • 1
  • Jian Wang
    • 4
  1. 1.Department of AnesthesiologyShengJing Hospital of China Medical UniversityShenyangChina
  2. 2.Department of Neurobiology, College of Basic MedicineChina Medical UniversityShenyangChina
  3. 3.Department of NeurologyFifth Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
  4. 4.Department of Anesthesiology and Critical Care Medicine, School of MedicineJohns Hopkins UniversityBaltimoreUSA

Personalised recommendations