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Published in: Journal of Neuroinflammation 1/2011

Open Access 01-12-2011 | Short report

Vascular endothelial growth factor-A (VEGF-A) and chemokine ligand-2 (CCL2) in amyotrophic lateral sclerosis (ALS) patients

Authors: Pawan K Gupta, Sudesh Prabhakar, Suresh Sharma, Akshay Anand

Published in: Journal of Neuroinflammation | Issue 1/2011

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Abstract

Background

Vascular endothelial growth factor-A (VEGF-A) and chemokne ligand-2 (CCL2) levels have been examined in Amyotrophic Lateral Sclerosis (ALS) patients in Western countries. We measured these values in North Indian ALS patients, since these patients display considerably enhanced survival duration.

Methods

Sporadic ALS patients were included on the basis of El Escorial criteria. VEGF-A and CCL2 levels were analyzed in serum and cerebrospinal fluid (CSF) of 50 ALS patients using enzyme linked immunosorbent assay (ELISA) and compared with normal controls. Their levels were adjusted for possible confounders like cigarette smoking, alcohol and meat consumption.

Results

Contrary to previous studies, VEGF-A was found to be elevated significantly in serum and CSF in ALS patient population studied. We also found an increase in CCL2 levels in CSF of these ALS patients. Serum and CSF from definite ALS revealed higher VEGF-A as compared to probable and possible ALS. CCL2 was unaltered between definite, probable and possible ALS. Univariate and multivariate analysis revealed a lack of association of smoking, alcohol and meat consumption with VEGF-A and CCL2 levels.

Conclusions

VEGF-A upregulation may indicate an activation of compensatory responses in ALS which may reflect or in fact account for increased survival of North Indian ALS patients after disease onset. The intrathecal synthesis of CCL2 suggests the involvement of adult neural stem cells and microglial activation in ALS pathogenesis which needs further investigation.
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Literature
1.
go back to reference Zheng C, Nennesmo I, Fadeel B, Henter JI: Vascular endothelial growth factor prolongs survival in a transgenic model of ALS. Ann Neurol. 2004, 56: 564-567. 10.1002/ana.20223.CrossRefPubMed Zheng C, Nennesmo I, Fadeel B, Henter JI: Vascular endothelial growth factor prolongs survival in a transgenic model of ALS. Ann Neurol. 2004, 56: 564-567. 10.1002/ana.20223.CrossRefPubMed
2.
go back to reference Li B, Xu W, Luo C, Gozal D, Liu R: VEGF-induced activation of the PI3-K/Akt pathway reduces mutant SOD1-mediated motor neuron cell death. Brain Res Mol Brain Res. 2003, 111: 155-164.CrossRefPubMed Li B, Xu W, Luo C, Gozal D, Liu R: VEGF-induced activation of the PI3-K/Akt pathway reduces mutant SOD1-mediated motor neuron cell death. Brain Res Mol Brain Res. 2003, 111: 155-164.CrossRefPubMed
3.
go back to reference Meng H, Zhang Z, Zhang R, Liu X, Wang L, Robin AM, Chopp M: Biphasic effects of exogenous VEGF on VEGF expression of adult neural progenitors. Neurosci Lett. 2006, 393: 97-101. 10.1016/j.neulet.2005.09.044.CrossRefPubMed Meng H, Zhang Z, Zhang R, Liu X, Wang L, Robin AM, Chopp M: Biphasic effects of exogenous VEGF on VEGF expression of adult neural progenitors. Neurosci Lett. 2006, 393: 97-101. 10.1016/j.neulet.2005.09.044.CrossRefPubMed
4.
go back to reference Henkel JS, Engelhardt JI, Siklos L, Simpson EP, Kim SH, Pan T, Goodman JC, Siddique T, Beers DR, Appel SH: Presence of dendritic cells, MCP-1, and activated microglia/macrophages in amyotrophic lateral sclerosis spinal cord tissue. Ann Neurol. 2004, 55: 221-235. 10.1002/ana.10805.CrossRefPubMed Henkel JS, Engelhardt JI, Siklos L, Simpson EP, Kim SH, Pan T, Goodman JC, Siddique T, Beers DR, Appel SH: Presence of dendritic cells, MCP-1, and activated microglia/macrophages in amyotrophic lateral sclerosis spinal cord tissue. Ann Neurol. 2004, 55: 221-235. 10.1002/ana.10805.CrossRefPubMed
5.
go back to reference Hughes PM, Allegrini PR, Rudin M, Perry VH, Mir AK, Wiessner C: Monocyte chemoattractant protein-1 deficiency is protective in a murine stroke model. J Cereb Blood Flow Metab. 2002, 22: 308-317.CrossRefPubMed Hughes PM, Allegrini PR, Rudin M, Perry VH, Mir AK, Wiessner C: Monocyte chemoattractant protein-1 deficiency is protective in a murine stroke model. J Cereb Blood Flow Metab. 2002, 22: 308-317.CrossRefPubMed
6.
go back to reference Huang DR, Wang J, Kivisakk P, Rollins BJ, Ransohoff RM: Absence of monocyte chemoattractant protein 1 in mice leads to decreased local macrophage recruitment and antigen-specific T helper cell type 1 immune response in experimental autoimmune encephalomyelitis. J Exp Med. 2001, 193: 713-726. 10.1084/jem.193.6.713.PubMedCentralCrossRefPubMed Huang DR, Wang J, Kivisakk P, Rollins BJ, Ransohoff RM: Absence of monocyte chemoattractant protein 1 in mice leads to decreased local macrophage recruitment and antigen-specific T helper cell type 1 immune response in experimental autoimmune encephalomyelitis. J Exp Med. 2001, 193: 713-726. 10.1084/jem.193.6.713.PubMedCentralCrossRefPubMed
7.
go back to reference Hong KH, Ryu J, Han KH: Monocyte chemoattractant protein-1-induced angiogenesis is mediated by vascular endothelial growth factor-A. Blood. 2005, 105: 1405-1407. 10.1182/blood-2004-08-3178.CrossRefPubMed Hong KH, Ryu J, Han KH: Monocyte chemoattractant protein-1-induced angiogenesis is mediated by vascular endothelial growth factor-A. Blood. 2005, 105: 1405-1407. 10.1182/blood-2004-08-3178.CrossRefPubMed
8.
go back to reference Cedarbaum JM, Stambler N, Malta E, Fuller C, Hilt D, Thurmond B, Nakanishi A: The ALSFRS-R: a revised ALS functional rating scale that incorporates assessmentsof respiratory function. BDNF ALS Study Group (Phase III). J Neurol Sci. 1999, 169: 13-21. 10.1016/S0022-510X(99)00210-5.CrossRefPubMed Cedarbaum JM, Stambler N, Malta E, Fuller C, Hilt D, Thurmond B, Nakanishi A: The ALSFRS-R: a revised ALS functional rating scale that incorporates assessmentsof respiratory function. BDNF ALS Study Group (Phase III). J Neurol Sci. 1999, 169: 13-21. 10.1016/S0022-510X(99)00210-5.CrossRefPubMed
9.
go back to reference Prabhakar S, Vinish M, Das CP, Anand A: Occurrence of PARK2 Mutations in a Never-Smoker Population with Parkinson's Disease in North India. Neuroepidemiology. 2010, 35: 152-159. 10.1159/000313855.CrossRefPubMed Prabhakar S, Vinish M, Das CP, Anand A: Occurrence of PARK2 Mutations in a Never-Smoker Population with Parkinson's Disease in North India. Neuroepidemiology. 2010, 35: 152-159. 10.1159/000313855.CrossRefPubMed
10.
go back to reference Bradley WG: Commentary on Professor Stephen Hawking's disability advice. Annals of Neurosciences. 2009, 16: 101-102. 10.5214/ans.0972.7531.2009.160303.CrossRef Bradley WG: Commentary on Professor Stephen Hawking's disability advice. Annals of Neurosciences. 2009, 16: 101-102. 10.5214/ans.0972.7531.2009.160303.CrossRef
11.
go back to reference Nalini A, Thennarasu K, Gourie-Devi M, Shenoy S, Kulshreshtha D: Clinical characteristics and survival pattern of 1,153 patients with amyotrophic lateral sclerosis: experience over 30 years from India. J Neurol Sci. 2008, 272: 60-70. 10.1016/j.jns.2008.04.034.CrossRefPubMed Nalini A, Thennarasu K, Gourie-Devi M, Shenoy S, Kulshreshtha D: Clinical characteristics and survival pattern of 1,153 patients with amyotrophic lateral sclerosis: experience over 30 years from India. J Neurol Sci. 2008, 272: 60-70. 10.1016/j.jns.2008.04.034.CrossRefPubMed
12.
go back to reference Sorenson EJ, Stalker AP, Kurland LT, Windebank AJ: Amyotrophic lateral sclerosis in Olmsted County, Minnesota, 1925 to 1998. Neurology. 2002, 59: 280-282.CrossRefPubMed Sorenson EJ, Stalker AP, Kurland LT, Windebank AJ: Amyotrophic lateral sclerosis in Olmsted County, Minnesota, 1925 to 1998. Neurology. 2002, 59: 280-282.CrossRefPubMed
13.
go back to reference Osuntokun BO, Adeuja AOG, Bademosi O: The prognosis of motor neuron disease in Nigerian Africans. A prospective study of 92 patients. Brain. 1974, 97: 385-394. 10.1093/brain/97.1.385.CrossRefPubMed Osuntokun BO, Adeuja AOG, Bademosi O: The prognosis of motor neuron disease in Nigerian Africans. A prospective study of 92 patients. Brain. 1974, 97: 385-394. 10.1093/brain/97.1.385.CrossRefPubMed
14.
go back to reference Nygren I, Larsson A, Johansson A, Askmark H: VEGF-A is increased in serum but not in spinal cord from patients with amyotrophic lateral sclerosis. Neuroreport. 2002, 13: 2199-201. 10.1097/00001756-200212030-00007.CrossRefPubMed Nygren I, Larsson A, Johansson A, Askmark H: VEGF-A is increased in serum but not in spinal cord from patients with amyotrophic lateral sclerosis. Neuroreport. 2002, 13: 2199-201. 10.1097/00001756-200212030-00007.CrossRefPubMed
15.
go back to reference Devos D, Moreau C, Lassalle P, Perez T, De Seze J, Brunaud-Danel V, Destée A, Tonnel AB, Just N: Low levels of the vascular endothelial growth factor in CSF from early ALS patients. Neurology. 2004, 62: 2127-2129.CrossRefPubMed Devos D, Moreau C, Lassalle P, Perez T, De Seze J, Brunaud-Danel V, Destée A, Tonnel AB, Just N: Low levels of the vascular endothelial growth factor in CSF from early ALS patients. Neurology. 2004, 62: 2127-2129.CrossRefPubMed
16.
go back to reference Cronin S, Greenway MJ, Ennis S, Kieran D, Green A, Prehn JH, Hardiman O: Elevated serum angiogenin levels in ALS. Neurology. 2006, 67: 1833-1836. 10.1212/01.wnl.0000244466.46020.47.CrossRefPubMed Cronin S, Greenway MJ, Ennis S, Kieran D, Green A, Prehn JH, Hardiman O: Elevated serum angiogenin levels in ALS. Neurology. 2006, 67: 1833-1836. 10.1212/01.wnl.0000244466.46020.47.CrossRefPubMed
17.
go back to reference McCloskey DP, Hintz TM, Scharfman HE: Modulation of vascular endothelial growth factor (VEGF) expression in motor neurons and its electrophysiological effects. Brain Res Bull. 2008, 76: 36-44. 10.1016/j.brainresbull.2007.11.018.PubMedCentralCrossRefPubMed McCloskey DP, Hintz TM, Scharfman HE: Modulation of vascular endothelial growth factor (VEGF) expression in motor neurons and its electrophysiological effects. Brain Res Bull. 2008, 76: 36-44. 10.1016/j.brainresbull.2007.11.018.PubMedCentralCrossRefPubMed
18.
go back to reference Bogaert E, Van Damme P, Poesen K, Dhondt J, Hersmus N, Kiraly D, Scheveneels W, Robberecht W, Van Den Bosch L: VEGF protects motor neurons against excitotoxicity by upregulation of GluR2. Neurobiol Aging. 2008 Bogaert E, Van Damme P, Poesen K, Dhondt J, Hersmus N, Kiraly D, Scheveneels W, Robberecht W, Van Den Bosch L: VEGF protects motor neurons against excitotoxicity by upregulation of GluR2. Neurobiol Aging. 2008
19.
go back to reference Madrigal JL, Leza JC, Polak P, Kalinin S, Feinstein DL: Astrocyte-derived MCP-1 mediates neuroprotective effects of noradrenaline. J Neurosci. 2009, 29: 263-267. 10.1523/JNEUROSCI.4926-08.2009.CrossRefPubMed Madrigal JL, Leza JC, Polak P, Kalinin S, Feinstein DL: Astrocyte-derived MCP-1 mediates neuroprotective effects of noradrenaline. J Neurosci. 2009, 29: 263-267. 10.1523/JNEUROSCI.4926-08.2009.CrossRefPubMed
20.
go back to reference Liu XS, Zhang ZG, Zhang RL, Gregg SR, Wang L, Yier T, Chopp M: Chemokine ligand 2 (CCL2) induces migration and differentiation of subventricular zone cells after stroke. J Neurosci Res. 2007, 85: 2120-2125. 10.1002/jnr.21359.CrossRefPubMed Liu XS, Zhang ZG, Zhang RL, Gregg SR, Wang L, Yier T, Chopp M: Chemokine ligand 2 (CCL2) induces migration and differentiation of subventricular zone cells after stroke. J Neurosci Res. 2007, 85: 2120-2125. 10.1002/jnr.21359.CrossRefPubMed
21.
go back to reference Magge SN, Malik SZ, Royo NC, Chen HI, Yu L, Snyder EY, O'Rourke DM, Watson DJ: Role of monocyte chemoattractant protein-1 (MCP-1/CCL2) in migration of neural progenitor cells toward glial tumors. J Neurosci Res. 2009, 87: 1547-1555. 10.1002/jnr.21983.CrossRefPubMed Magge SN, Malik SZ, Royo NC, Chen HI, Yu L, Snyder EY, O'Rourke DM, Watson DJ: Role of monocyte chemoattractant protein-1 (MCP-1/CCL2) in migration of neural progenitor cells toward glial tumors. J Neurosci Res. 2009, 87: 1547-1555. 10.1002/jnr.21983.CrossRefPubMed
22.
go back to reference Marumo T, Schini-Kerth VB, Busse R: Vascular endothelial growth factor activates nuclear factor-kappaB and induces monocyte chemoattractant protein-1 in bovine retinal endothelial cells. Diabetes. 1999, 48: 1131-1137. 10.2337/diabetes.48.5.1131.CrossRefPubMed Marumo T, Schini-Kerth VB, Busse R: Vascular endothelial growth factor activates nuclear factor-kappaB and induces monocyte chemoattractant protein-1 in bovine retinal endothelial cells. Diabetes. 1999, 48: 1131-1137. 10.2337/diabetes.48.5.1131.CrossRefPubMed
23.
go back to reference Schichor C, Birnbaum T, Etminan N, Schnell O, Grau S, Miebach S, Aboody K, Padovan C, Straube A, Tonn JC, Goldbrunner R: Vascular endothelial growth factor A contributes to glioma-induced migration of human marrow stromal cells (hMSC). Exp Neurol. 2006, 199: 301-310. 10.1016/j.expneurol.2005.11.027.CrossRefPubMed Schichor C, Birnbaum T, Etminan N, Schnell O, Grau S, Miebach S, Aboody K, Padovan C, Straube A, Tonn JC, Goldbrunner R: Vascular endothelial growth factor A contributes to glioma-induced migration of human marrow stromal cells (hMSC). Exp Neurol. 2006, 199: 301-310. 10.1016/j.expneurol.2005.11.027.CrossRefPubMed
24.
go back to reference El-Badri NS, Hakki A, Saporta S, Liang X, Madhusodanan S, Willing AE, Sanberg CD, Sanberg PR: Cord blood mesenchymal stem cells: Potential use in neurological disorders. Stem Cells Dev. 2006, 15: 497-506. 10.1089/scd.2006.15.497.CrossRefPubMed El-Badri NS, Hakki A, Saporta S, Liang X, Madhusodanan S, Willing AE, Sanberg CD, Sanberg PR: Cord blood mesenchymal stem cells: Potential use in neurological disorders. Stem Cells Dev. 2006, 15: 497-506. 10.1089/scd.2006.15.497.CrossRefPubMed
Metadata
Title
Vascular endothelial growth factor-A (VEGF-A) and chemokine ligand-2 (CCL2) in amyotrophic lateral sclerosis (ALS) patients
Authors
Pawan K Gupta
Sudesh Prabhakar
Suresh Sharma
Akshay Anand
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2011
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-8-47

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