Intranasal Delivery of Granulocyte Colony-Stimulating Factor Enhances Its Neuroprotective Effects Against Ischemic Brain Injury in Rats

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• 作者：Bao-liang Sun ; Mei-qing He ; Xiang-yu Han ; Jing-yi Sun…
• 关键词：G ; CSF ; BBB ; Brain ischemia ; HO ; 1
• 刊名：Molecular Neurobiology
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：53
• 期：1
• 页码：320-330
• 全文大小：9,291 KB
• 参考文献：1.Rother J (2008) Neuroprotection does not work. Stroke 39(2):523–524CrossRef PubMed
  2.Ginsberg MD (2009) Current status of neuroprotection for cerebral ischemia: synoptic overview. Stroke 40(3 Suppl):S111–S114CrossRef PubMed PubMedCentral
  3.Hussain MS, Shuaib A (2008) Research into neuroprotection must continue … but with a different approach. Stroke 39(2):521–522CrossRef PubMed
  4.Lin R et al (2009) Mechanical approaches combined with intra-arterial pharmacological therapy are associated with higher recanalization rates than either intervention alone in revascularization of acute carotid terminus occlusion. Stroke 40(6):2092–2097CrossRef PubMed
  5.Lee K et al (2007) Beyond intravenous thrombolysis. CNS Spectr 12(8):609–614PubMed
  6.Cao G et al (2002) In vivo delivery of a Bcl-xL fusion protein containing the TAT protein transduction domain protects against ischemic brain injury and neuronal apoptosis. J Neurosci 22(13):5423–5431PubMed
  7.Yu YP et al (2005) Intranasal recombinant human erythropoietin protects rats against focal cerebral ischemia. Neurosci Lett 387(1):5–10CrossRef PubMed
  8.Zhao HM et al (2004) Intranasal delivery of nerve growth factor to protect the central nervous system against acute cerebral infarction. Chin Med Sci J 19(4):257–261PubMed
  9.Liu XF et al (2001) Intranasal administration of insulin-like growth factor-I bypasses the blood
  ain barrier and protects against focal cerebral ischemic damage. J Neurol Sci 187(1–2):91–97CrossRef PubMed
  10.Dhuria SV, Hanson LR, and Frey WH 2nd (2010) Intranasal delivery to the central nervous system: mechanisms and experimental considerations. J Pharm Sci. 99(4):1654–1673. doi:10.​1002/​jps.​21924 .
  11.Thorne RG et al (1995) Quantitative analysis of the olfactory pathway for drug delivery to the brain. Brain Res 692(1–2):278–282CrossRef PubMed
  12.Hanson LR, Frey WH 2nd (2007) Strategies for intranasal delivery of therapeutics for the prevention and treatment of neuroAIDS. J Neuroimmune Pharmacol 2(1):81–86CrossRef PubMed
  13.Xu L et al (2008) Leptin inhibits 4-aminopyridine- and pentylenetetrazole-induced seizures and AMPAR-mediated synaptic transmission in rodents. J Clin Invest 118(1):272–280CrossRef PubMed PubMedCentral
  14.Veronesi MC, Kubek DJ, Kubek MJ (2007) Intranasal delivery of a thyrotropin-releasing hormone analog attenuates seizures in the amygdala-kindled rat. Epilepsia 48(12):2280–2286PubMed
  15.Gozes I et al (1996) Neuroprotective strategy for Alzheimer disease: intranasal administration of a fatty neuropeptide. Proc Natl Acad Sci U S A 93(1):427–432CrossRef PubMed PubMedCentral
  16.Reger MA et al (2008) Intranasal insulin improves cognition and modulates beta-amyloid in early AD. Neurology 70(6):440–448CrossRef PubMed
  17.Nakayama T et al (2007) Intranasal administration of E-selectin to induce immunological tolerization can suppress subarachnoid hemorrhage-induced vasospasm implicating immune and inflammatory mechanisms in its genesis. Brain Res 1132(1):177–184CrossRef PubMed PubMedCentral
  18.Sun BL et al (2010) Intranasal delivery of calcitonin gene-related peptide reduces cerebral vasospasm in rats. Front Biosci (Elite Ed) 2:1502–1513CrossRef
  19.Ying W et al (2007) Intranasal administration with NAD+ profoundly decreases brain injury in a rat model of transient focal ischemia. Front Biosci 12:2728–2734CrossRef PubMed
  20.Wei G et al (2007) Intranasal administration of a PARG inhibitor profoundly decreases ischemic brain injury. Front Biosci 12:4986–4996CrossRef PubMed
  21.Akpan N et al (2011) Intranasal delivery of caspase-9 inhibitor reduces caspase-6-dependent axon/neuron loss and improves neurological function after stroke. J Neurosci 31(24):8894–8904CrossRef PubMed PubMedCentral
  22.Donega V et al (2013) Intranasal mesenchymal stem cell treatment for neonatal brain damage: long-term cognitive and sensorimotor improvement. PLoS One 8(1):e51253CrossRef PubMed PubMedCentral
  23.Nagata S et al (1986) Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor. Nature 319(6052):415–418CrossRef PubMed
  24.Welte K et al (1985) Purification and biochemical characterization of human pluripotent hematopoietic colony-stimulating factor. Proc Natl Acad Sci U S A 82(5):1526–1530CrossRef PubMed PubMedCentral
  25.Hasselblatt M et al (2007) Granulocyte-colony stimulating factor (G-CSF) and G-CSF receptor expression in human ischemic stroke. Acta Neuropathol 113(1):45–51CrossRef PubMed
  26.Schneider A et al (2005) The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis. J Clin Invest 115(8):2083–2098CrossRef PubMed PubMedCentral
  27.Diederich K et al (2009) The role of granulocyte-colony stimulating factor (G-CSF) in the healthy brain: a characterization of G-CSF-deficient mice. J Neurosci 29(37):11572–11581CrossRef PubMed
  28.Gibson CL, Bath PM, Murphy SP (2005) G-CSF reduces infarct volume and improves functional outcome after transient focal cerebral ischemia in mice. J Cereb Blood Flow Metab 25(4):431–439CrossRef PubMed
  29.Solaroglu I et al (2006) A novel neuroprotectant granulocyte-colony stimulating factor. Stroke 37(4):1123–1128CrossRef PubMed
  30.Solaroglu I, Jadhav V, Zhang JH (2007) Neuroprotective effect of granulocyte-colony stimulating factor. Front Biosci 12:712–724CrossRef PubMed
  31.Charles MS et al (2012) Role of the pituitary-adrenal axis in granulocyte-colony stimulating factor-induced neuroprotection against hypoxia-ischemia in neonatal rats. Neurobiol Dis 47(1):29–37CrossRef PubMed PubMedCentral
  32.Sugiyama Y et al (2011) Granulocyte colony-stimulating factor enhances arteriogenesis and ameliorates cerebral damage in a mouse model of ischemic stroke. Stroke 42(3):770–775CrossRef PubMed
  33.Minnerup J et al (2008) Meta-analysis of the efficacy of granulocyte-colony stimulating factor in animal models of focal cerebral ischemia. Stroke 39(6):1855–1861CrossRef PubMed
  34.Zhang F et al (1998) U-74389G suppresses lipid peroxidation and apoptosis following focal cerebral ischemia and reperfusion in rats. Chin Med J (Engl) 111(9):838–841
  35.Sun BL et al (2007) Effects of extract of ginkgo biloba on intracranial pressure, cerebral perfusion pressure, and cerebral blood flow in a rat model of subarachnoid haemorrhage. Int J Neurosci 117(5):655–665CrossRef PubMed
  36.Sun BL et al (2009) Dynamic alterations of cerebral pial microcirculation during experimental subarachnoid hemorrhage. Cell Mol Neurobiol 29(2):235–241CrossRef PubMed
  37.Fletcher L et al (2009) Intranasal delivery of erythropoietin plus insulin-like growth factor-I for acute neuroprotection in stroke. Laboratory investigation. J Neurosurg 111(1):164–170CrossRef PubMed
  38.Yang J-P et al (2009) The dose-effectiveness of intranasal VEGF in treatment of experimental stroke. Neurosci Lett 461(3):212–216CrossRef PubMed
  39.Zhang F et al (2010) Enhanced delivery of erythropoietin across the blood
  ain barrier for neuroprotection against ischemic neuronal injury. Transl Stroke Res 1(2):113–121CrossRef PubMed PubMedCentral
  40.Zhang F et al (2009) When hypothermia meets hypotension and hyperglycemia: the diverse effects of adenosine 5′-monophosphate on cerebral ischemia in rats. J Cereb Blood Flow Metab 29(5):1022–1034CrossRef PubMed PubMedCentral
  41.Bar-Yehuda S et al (2002) Agonists to the A3 adenosine receptor induce G-CSF production via NF-[kappa] B activation: a new class of myeloprotective agents. Exp Hematol 30(12):1390–1398CrossRef PubMed
  42.Ding Y et al (2004) Local saline infusion into ischemic territory induces regional brain cooling and neuroprotection in rats with transient middle cerebral artery occlusion. Neurosurgery 54(4):956–964, discussion 964–5CrossRef PubMed
  43.Longa EZ et al (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20(1):84–91CrossRef PubMed
  44.Chen J et al (2001) Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke 32(4):1005–1011CrossRef PubMed
  45.Matsumoto Y et al (2004) Na+/H+ exchanger inhibitor, SM-20220, is protective against excitotoxicity in cultured cortical neurons. Stroke 35(1):185–190CrossRef PubMed
  46.Asanuma M et al (1993) Ischemia-induced changes in alpha-tubulin and beta-actin mRNA in the gerbil brain and effects of bifemelane hydrochloride. Brain Res 600(2):243–248CrossRef PubMed
  47.Sehara Y et al (2007) Potentiation of neurogenesis and angiogenesis by G-CSF after focal cerebral ischemia in rats. Brain Res 1151:142–149CrossRef PubMed
  48.Seki T (2002) Hippocampal adult neurogenesis occurs in a microenvironment provided by PSA-NCAM-expressing immature neurons. J Neurosci Res 69(6):772–783CrossRef PubMed
  49.Zhang F et al (2007) Neuroprotective effects of leptin against ischemic injury induced by oxygen-glucose deprivation and transient cerebral ischemia. Stroke 38(8):2329–2336CrossRef PubMed
  50.Solaroglu I et al (2009) Granulocyte colony-stimulating factor protects the brain against experimental stroke via inhibition of apoptosis and inflammation. Neurol Res 31(2):167–172CrossRef PubMed
  51.Lu CZ, Xiao BG (2007) Neuroprotection of G-CSF in cerebral ischemia. Front Biosci 12:2869–2875CrossRef PubMed
  52.Bano D, Nicotera P (2007) Ca2+ signals and neuronal death in brain ischemia. Stroke 38(2):674–676CrossRef PubMed
  53.Hori M et al (1994) Beta-adrenergic stimulation disassembles microtubules in neonatal rat cultured cardiomyocytes through intracellular Ca2+ overload. Circ Res 75(2):324–334CrossRef PubMed
  54.Moreira TJTP et al (2007) Reduced HO-1 protein expression is associated with more severe neurodegeneration after transient ischemia induced by cortical compression in diabetic Goto-Kakizaki rats. J Cereb Blood Flow Metab 27(10):1710–1723CrossRef PubMed
  55.Nariman P, Masako Y, Mahin DM (1999) Overexpression of heme oxygenase-1 is neuroprotective in a model of permanent middle cerebral artery occlusion in transgenic mice. J Neurochem 72(3):1187–1203
  56.Kim KC et al (2010) Up-regulation of Nrf2-mediated heme oxygenase-1 expression by eckol, a phlorotannin compound, through activation of Erk and PI3K/Akt. Int J Biochem Cell Biol 42(2):297CrossRef PubMed
  57.Martin D et al (2004) Regulation of heme oxygenase-1 expression through the phosphatidylinositol 3-kinase/Akt pathway and the Nrf2 transcription factor in response to the antioxidant phytochemical carnosol. J Biol Chem 279(10):8919–8929CrossRef PubMed
  58.Jung KH et al (2006) Granulocyte colony-stimulating factor stimulates neurogenesis via vascular endothelial growth factor with STAT activation. Brain Res 1073–1074:190–201CrossRef PubMed
  59.Ding J. et al (2009) Rho kinase inhibitor Fasudil induces neuroprotection and neurogenesis partially through astrocyte-derived G-CSF. Brain Behav Immun. 23(8):1083–1088. doi:10.​1016/​j.​bbi.​2009.​05.​002
  60.Sanchez-Ramos J et al (2009) Granulocyte colony stimulating factor decreases brain amyloid burden and reverses cognitive impairment in Alzheimer’s mice. Neuroscience 163(1):55–72CrossRef PubMed
  61.Lee ST et al (2005) Granulocyte colony-stimulating factor enhances angiogenesis after focal cerebral ischemia. Brain Res 1058(1–2):120–128CrossRef PubMed
  62.Bussolino F et al (1989) Granulocyte- and granulocyte-macrophage-colony stimulating factors induce human endothelial cells to migrate and proliferate. Nature 337(6206):471–473CrossRef PubMed
  63.Thorne RG et al (2004) Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration. Neuroscience 127(2):481–496CrossRef PubMed
  64.Balin BJ et al (1986) Avenues for entry of peripherally administered protein to the central nervous system in mouse, rat, and squirrel monkey. J Comp Neurol 251(2):260–280CrossRef PubMed
  65.Baker H, Spencer RF (1986) Transneuronal transport of peroxidase-conjugated wheat germ agglutinin (WGA-HRP) from the olfactory epithelium to the brain of the adult rat. Exp Brain Res 63(3):461–473CrossRef PubMed
  66.Pollock H et al (1997) Perivascular spaces in the basal ganglia of the human brain: their relationship to lacunes. J Anat 191(Pt 3):337–346CrossRef PubMed PubMedCentral
  67.Rennels ML et al (1985) Evidence for a ‘paravascular’ fluid circulation in the mammalian central nervous system, provided by the rapid distribution of tracer protein throughout the brain from the subarachnoid space. Brain Res 326(1):47–63CrossRef PubMed
  68.Rennels ML, Blaumanis OR, Grady PA (1990) Rapid solute transport throughout the brain via paravascular fluid pathways. Adv Neurol 52:431–439PubMed
  69.Zhao LR et al (2007) Brain repair by hematopoietic growth factors in a rat model of stroke. Stroke 38(9):2584–2591CrossRef PubMed
  70.Kotto-Kome AC et al (2004) Evidence that the granulocyte colony-stimulating factor (G-CSF) receptor plays a role in the pharmacokinetics of G-CSF and PegG-CSF using a G-CSF-R KO model. Pharmacol Res 50(1):55–58CrossRef PubMed
  71.Kirsch F, Kruger C, Schneider A (2008) The receptor for granulocyte-colony stimulating factor (G-CSF) is expressed in radial glia during development of the nervous system. BMC Dev Biol 8:32CrossRef PubMed PubMedCentral
  72.Panopoulos AD, Watowich SS (2008) Granulocyte colony-stimulating factor: molecular mechanisms of action during steady state and ‘emergency’ hematopoiesis. Cytokine 42(3):277–288CrossRef PubMed PubMedCentral
  73.Bai GR et al (2006) Inositol 1,4,5-trisphosphate receptor type 1 phosphorylation and regulation by extracellular signal-regulated kinase. Biochem Biophys Res Commun 348(4):1319–1327CrossRef PubMed
  74.Khan MT et al (2006) Akt kinase phosphorylation of inositol 1,4,5-trisphosphate receptors. J Biol Chem 281(6):3731–3737CrossRef PubMed
  75.Chen BS, Roche KW (2007) Regulation of NMDA receptors by phosphorylation. Neuropharmacology 53(3):362–368CrossRef PubMed PubMedCentral
  76.Zhang M et al (2013) Emerging roles of Nrf2 and phase II antioxidant enzymes in neuroprotection. Prog Neurobiol 100:30–47CrossRef PubMed PubMedCentral
  77.Wang L et al (2012) Arsenic modulates heme oxygenase-1, interleukin-6, and vascular endothelial growth factor expression in endothelial cells: roles of ROS, NF-kappaB, and MAPK pathways. Arch Toxicol 86(6):879–896CrossRef PubMed
  78.Ryu MJ et al (2014) 7,8-Dihydroxyflavone protects human keratinocytes against oxidative stress-induced cell damage via the ERK and PI3K/Akt-mediated Nrf2/HO-1 signaling pathways. Int J Mol Med 33(4):964–970PubMed
  79.Rada P et al (2012) Structural and functional characterization of Nrf2 degradation by the glycogen synthase kinase 3/beta-TrCP axis. Mol Cell Biol 32(17):3486–3499CrossRef PubMed PubMedCentral
  80.Zhang F et al (2012) Pharmacological induction of heme oxygenase-1 by a triterpenoid protects neurons against ischemic injury. Stroke 43(5):1390–1397CrossRef PubMed PubMedCentral
  81.Zhang M et al (2014) Omega-3 fatty acids protect the brain against ischemic injury by activating Nrf2 and upregulating heme oxygenase 1. J Neurosci 34(5):1903–1915CrossRef PubMed PubMedCentral
  82.Piao CS et al (2009) The role of stem cell factor and granulocyte-colony stimulating factor in brain repair during chronic stroke. J Cereb Blood Flow Metab 29(4):759–770CrossRef PubMed
  83.Shyu WC et al (2004) Functional recovery of stroke rats induced by granulocyte colony-stimulating factor-stimulated stem cells. Circulation 110(13):1847–1854CrossRef PubMed
  84.Strecker J-K et al (2010) Effects of G-CSF treatment on neutrophil mobilization and neurological outcome after transient focal ischemia. Exp Neurol 222(1):108–113CrossRef PubMed
  85.Popa-Wagner A et al (2010) Effects of granulocyte-colony stimulating factor after stroke in aged rats. Stroke 41(5):1027–1031CrossRef PubMed
  86.Lu F et al (2014) Neuroprotection of granulocyte colony-stimulating factor during the acute phase of transient forebrain ischemia in gerbils. Brain Res 1548:49–55CrossRef PubMed
  
• 作者单位：Bao-liang Sun (1) (2)
  Mei-qing He (1) (3)
  Xiang-yu Han (1) (4)
  Jing-yi Sun (1) (5)
  Ming-feng Yang (1) (2)
  Hui Yuan (1) (2)
  Cun-dong Fan (1) (2)
  Shuai Zhang (1) (2)
  Lei-lei Mao (1) (2) (9)
  Da-wei Li (1) (2)
  Zong-yong Zhang (1) (2)
  Cheng-bi Zheng (1) (2) (6)
  Xiao-yi Yang (1) (2)
  Yang V. Li (7)
  R. Anne Stetler (8) (9)
  Jun Chen (8) (9)
  Feng Zhang (1) (8) (9)
  
  1. Key Laboratory of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, Shandong, 271000, China
  2. Department of Neurology, Affiliated Hospital of Taishan Medical University, Taian, Shandong, 271000, China
  3. Department of Neurology, Taishan Hospital, Taian, Shandong, 271000, China
  4. Department of Emergency, Jining People’s Hospital, Jining, Shandong, 272000, China
  5. College of Basic Medicine, Taishan Medical University, Taian, Shandong, 271016, China
  9. Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, PA, 15260, USA
  6. Library, Taishan Medical University, Taian, Shandong, 271016, China
  7. Department of Biomedical Sciences, Ohio University Heritage College of Osteopathic Medicine, Athens, OH, 45701, USA
  8. Department of Neurology and Center of Cerebrovascular Disease Research, University of Pittsburgh, Pittsburgh, PA, USA
  
• 刊物主题：Neurosciences; Neurobiology; Cell Biology; Neurology;
• 出版者：Springer US
• ISSN：1559-1182

文摘

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor with strong neuroprotective properties. However, it has limited capacity to cross the blood-brain barrier and thus potentially limiting its protective capacity. Recent studies demonstrated that intranasal drug administration is a promising way in delivering neuroprotective agents to the central nervous system. The current study therefore aimed at determining whether intranasal administration of G-CSF increases its delivery to the brain and its neuroprotective effect against ischemic brain injury. Transient focal cerebral ischemia in rat was induced with middle cerebral artery occlusion. Our resulted showed that intranasal administration is 8–12 times more effective than subcutaneous injection in delivering G-CSF to cerebrospinal fluid and brain parenchyma. Intranasal delivery enhanced the protective effects of G-CSF against ischemic injury in rats, indicated by decreased infarct volume and increased recovery of neurological function. The neuroprotective mechanisms of G-CSF involved enhanced upregulation of HO-1 and reduced calcium overload following ischemia. Intranasal G-CSF application also promoted angiogenesis and neurogenesis following brain ischemia. Taken together, G-CSF is a legitimate neuroprotective agent and intranasal administration of G-CSF is more effective in delivery and neuroprotection and could be a practical approach in clinic.