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Immunity & Ageing
Published in: Immunity & Ageing 1/2014

Open Access 01-12-2014 | Research

Characterization of recovery, repair, and inflammatory processes following contusion spinal cord injury in old female rats: is age a limitation?

Authors: Mitra J Hooshmand, Manuel D Galvan, Elizabeth Partida, Aileen J Anderson

Published in: Immunity & Ageing | Issue 1/2014

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Abstract

Background

Although the incidence of spinal cord injury (SCI) is steadily rising in the elderly human population, few studies have investigated the effect of age in rodent models. Here, we investigated the effect of age in female rats on spontaneous recovery and repair after SCI. Young (3 months) and aged (18 months) female rats received a moderate contusion SCI at T9. Behavioral recovery was assessed, and immunohistocemical and stereological analyses performed.

Results

Aged rats demonstrated greater locomotor deficits compared to young, beginning at 7 days post-injury (dpi) and lasting through at least 28 dpi. Unbiased stereological analyses revealed a selective increase in percent lesion area and early (2 dpi) apoptotic cell death caudal to the injury epicenter in aged versus young rats. One potential mechanism for these differences in lesion pathogenesis is the inflammatory response; we therefore assessed humoral and cellular innate immune responses. No differences in either acute or chronic serum complement activity, or acute neutrophil infiltration, were observed between age groups. However, the number of microglia/macrophages present at the injury epicenter was increased by 50% in aged animals versus young.

Conclusions

These data suggest that age affects recovery of locomotor function, lesion pathology, and microglia/macrophage response following SCI.
Appendix
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Literature
1.
Cifu DX, Seel RT, Kreutzer JS, Marwitz J, McKinley WO, Wisor D: Age, outcome, and rehabilitation costs after tetraplegia spinal cord injury. Neurorehabilitation. 1999, 12 (3): 177-185.
2.
Dai LY: Acute central cervical cord injury: the effect of age upon prognosis. Inj Int J Care Inj. 2001, 32 (3): 195-199. 10.1016/S0020-1383(00)00176-5.CrossRef
3.
Furlan JC, Bracken MB, Fehlings MG: Is age a key determinant of mortality and neurological outcome after acute traumatic spinal cord injury?. Neurobiol Aging. 2010, 31 (3): 434-446. 10.1016/j.neurobiolaging.2008.05.003.CrossRefPubMed
4.
Fehlings MG, Furlan JC: Effect of age on spinal cord injury. J Neurosurg Spine. 2007, 7 (3): 275-276. 10.3171/SPI-07/09/275. discussion 276CrossRefPubMed
5.
Gwak YS, Hains BC, Johnson KM, Hulsebosch CE: Effect of age at time of spinal cord injury on behavioral outcomes in rat. J Neurotrauma. 2004, 21 (8): 983-993. 10.1089/0897715041650999.CrossRefPubMed
6.
Genovese T, Genovese T, Mazzon E, Di Paola R, Crisafulli C, Muia C, Bramanti P, Cuzzocrea S: Increased oxidative-related mechanisms in the spinal cord injury in old rats. Neurosci Lett. 2006, 393 (2–3): 141-146.CrossRefPubMed
7.
Siegenthaler MM, Berchtold NC, Cotman CW, Keirstead HS: Voluntary running attenuates age-related deficits following SCI. Exp Neurol. 2008, 210 (1): 207-216. 10.1016/j.expneurol.2007.10.019.PubMedCentralCrossRefPubMed
8.
CDRF: Spinal Cord Injury Information Network. 2008, Birmingham: University of Alabama
9.
Chaovipoch P, Jelks KA, Gerhold LM, West EJ, Chongthammakun S, Floyd CL: 17beta-estradiol is protective in spinal cord injury in post- and pre-menopausal rats. J Neurotrauma. 2006, 23 (6): 830-852. 10.1089/neu.2006.23.830.CrossRefPubMed
10.
Siegenthaler MM, Ammon DL, Keirstead HS: Myelin pathogenesis and functional deficits following SCI are age-associated. Exp Neurol. 2008, 213 (2): 363-371. 10.1016/j.expneurol.2008.06.015.PubMedCentralCrossRefPubMed
11.
Jaerve A, Kruse F, Malik K, Hartung HP, Muller HW: Age-dependent modulation of cortical transcriptomes in spinal cord injury and repair. PLoS ONE. 2012, 7 (12): e49812-10.1371/journal.pone.0049812.PubMedCentralCrossRefPubMed
12.
Kumamaru H, Saiwai H, Ohkawa Y, Yamada H, Iwamoto Y, Okada S: Age-related differences in cellular and molecular profiles of inflammatory responses after spinal cord injury. J Cell Physiol. 2012, 227 (4): 1335-1346. 10.1002/jcp.22845.CrossRefPubMed
13.
Long JM, Mouton PR, Jucker M, Ingram DK: What counts in brain aging? Design-based stereological analysis of cell number. J Gerontol A Biol Sci Med Sci. 1999, 54 (10): B407-B417. 10.1093/gerona/54.10.B407.CrossRefPubMed
14.
Laing AC, Cox R, Tetzlaff W, Oxland T: Effects of advanced age on the morphometry and degenerative state of the cervical spine in a rat model. Anat Rec (Hoboken). 2011, 294 (8): 1326-1336. 10.1002/ar.21436.CrossRef
15.
Scheff SW, Rabchevsky AG, Fugaccia I, Main JA, Lumpp JE: Experimental modeling of spinal cord injury: characterization of a force-defined injury device. J Neurotrauma. 2003, 20 (2): 179-193. 10.1089/08977150360547099.CrossRefPubMed
16.
Nishi RA, Liu H, Chu Y, Hamamura M, Su MY, Nalcioglu O, Anderson AJ: Behavioral, histological, and ex vivo magnetic resonance imaging assessment of graded contusion spinal cord injury in mice. J Neurotrauma. 2007, 24 (4): 674-689. 10.1089/neu.2006.0204.CrossRefPubMed
17.
Hamers FP, Lankhorst AJ, van Laar TJ, Veldhuis WB, Gispen WH: Automated quantitative gait analysis during overground locomotion in the rat: its application to spinal cord contusion and transection injuries. J Neurotrauma. 2001, 18 (2): 187-201. 10.1089/08977150150502613.CrossRefPubMed
18.
Vrinten DH, Hamers FF: ‘CatWalk’ automated quantitative gait analysis as a novel method to assess mechanical allodynia in the rat; a comparison with von Frey testing. Pain. 2003, 102 (1–2): 203-209.CrossRefPubMed
19.
Bresnahan JC, Beattie MS, Todd FD, Noyes DH: A behavioral and anatomical analysis of spinal cord injury produced by a feedback-controlled impaction device. Exp Neurol. 1987, 95 (3): 548-570. 10.1016/0014-4886(87)90299-8.CrossRefPubMed
20.
Guth L, Zhang Z, Steward O: The unique histopathological responses of the injured spinal cord. Implications for neuroprotective therapy. Ann N Y Acad Sci. 1999, 890: 366-384. 10.1111/j.1749-6632.1999.tb08017.x.CrossRefPubMed
21.
Jaerve A, Schiwy N, Schmitz C, Mueller HW: Differential effect of aging on axon sprouting and regenerative growth in spinal cord injury. Exp Neurol. 2011, 231 (2): 284-294. 10.1016/j.expneurol.2011.07.002.CrossRefPubMed
22.
Liu XZ, Xu XM, Hu R, Du C, Zhang SX, McDonald JW, Dong HX, Wu YJ, Fan GS, Jacquin MF, Hsu CY, Choi DW: Neuronal and glial apoptosis after traumatic spinal cord injury. J Neurosci. 1997, 17 (14): 5395-5406.PubMed
23.
Popovich PG, Guan Z, Wei P, Huitinga I, van Rooijen N, Stokes BT: Depletion of hematogenous macrophages promotes partial hindlimb recovery and neuroanatomical repair after experimental spinal cord injury. Exp Neurol. 1999, 158 (2): 351-365. 10.1006/exnr.1999.7118.CrossRefPubMed
24.
Sroga JM, Jones TB, Kigerl KA, McGaughy VM, Popovich PG: Rats and mice exhibit distinct inflammatory reactions after spinal cord injury. J Comp Neurol. 2003, 462 (2): 223-240. 10.1002/cne.10736.CrossRefPubMed
25.
Gris D, Marsh DR, Oatway MA, Chen Y, Hamilton EF, Dekaban GA, Weaver LC: Transient blockade of the CD11d/CD18 integrin reduces secondary damage after spinal cord injury, improving sensory, autonomic, and motor function. J Neurosci. 2004, 24 (16): 4043-4051. 10.1523/JNEUROSCI.5343-03.2004.CrossRefPubMed
26.
Fleming JC, Norenberg MD, Ramsay DA, Dekaban GA, Marcillo AE, Saenz AD, Pasquale-Styles M, Dietrich WD, Weaver LC: The cellular inflammatory response in human spinal cords after injury. Brain. 2006, 129 (Pt 12): 3249-3269.CrossRefPubMed
27.
Beck KD, Nguyen HX, Galvan MD, Salazar DL, Woodruff TM, Anderson AJ: Quantitative analysis of cellular inflammation after traumatic spinal cord injury: evidence for a multiphasic inflammatory response in the acute to chronic environment. Brain. 2010, 133 (Pt 2): 433-447.PubMedCentralCrossRefPubMed
28.
Anderson AJ, Robert S, Huang W, Young W, Cotman CW: Activation of complement pathways after contusion-induced spinal cord injury. J Neurotrauma. 2004, 21 (12): 1831-1846. 10.1089/neu.2004.21.1831.CrossRefPubMed
29.
Cole DS, Hughes TR, Gasque P, Morgan BP: Complement regulator loss on apoptotic neuronal cells causes increased complement activation and promotes both phagocytosis and cell lysis. Mol Immunol. 2006, 43 (12): 1953-1964. 10.1016/j.molimm.2005.11.015.CrossRefPubMed
30.
Ziporen L, Donin N, Shmushkovich T, Gross A, Fishelson Z: Programmed necrotic cell death induced by complement involves a Bid-dependent pathway. J Immunol. 2009, 182 (1): 515-521. 10.4049/jimmunol.182.1.515.CrossRefPubMed
31.
Rodakowski J, Skidmore ER, Anderson SJ, Begley A, Jensen MP, Buhule OD, Boninger ML: Additive effect of Age on disability for individuals with spinal cord injuries. Arch Phys Med Rehabil. 2014, 95 (6): 1076-1082. 10.1016/j.apmr.2014.01.022.PubMedCentralCrossRefPubMed
32.
Selvarajah S, Hammond ER, Haider AH, Abularrage CJ, Becker D, Dhiman N, Hyder O, Gupta D, Black JH, Schneider EB: The burden of acute traumatic spinal cord injury among adults in the united states: an update. J Neurotrauma. 2014, 31 (3): 228-238. 10.1089/neu.2013.3098.CrossRefPubMed
33.
Carlson SL, Parrish ME, Springer JE, Doty K, Dossett L: Acute inflammatory response in spinal cord following impact injury. Exp Neurol. 1998, 151 (1): 77-88. 10.1006/exnr.1998.6785.CrossRefPubMed
34.
Popovich PG, Wei P, Stokes BT: Cellular inflammatory response after spinal cord injury in Sprague–Dawley and Lewis rats. J Comp Neurol. 1997, 377 (3): 443-464. 10.1002/(SICI)1096-9861(19970120)377:3<443::AID-CNE10>3.0.CO;2-S.CrossRefPubMed
35.
Rebhun J, Madorsky JG, Glovsky MM: Proteins of the complement system and acute phase reactants in sera of patients with spinal cord injury. Ann Allergy. 1991, 66 (4): 335-338.PubMed
36.
Duce JA, Hollander W, Jaffe R, Abraham CR: Activation of early components of complement targets myelin and oligodendrocytes in the aged rhesus monkey brain. Neurobiol Aging. 2006, 27 (4): 633-644. 10.1016/j.neurobiolaging.2005.03.027.CrossRefPubMed
37.
Nagra RM, Becher B, Tourtellotte WW, Antel JP, Gold D, Paladino T, Smith RA, Nelson JR, Reynolds WF: Immunohistochemical and genetic evidence of myeloperoxidase involvement in multiple sclerosis. J Neuroimmunol. 1997, 78 (1–2): 97-107.CrossRefPubMed
38.
Reynolds WF, Rhees J, Maciejewski D, Paladino T, Sieburg H, Maki RA, Masliah E: Myeloperoxidase polymorphism is associated with gender specific risk for Alzheimer’s disease. Exp Neurol. 1999, 155 (1): 31-41. 10.1006/exnr.1998.6977.CrossRefPubMed
39.
Kyrkanides S, O'Banion MK, Whiteley PE, Daeschner JC, Olschowka JA: Enhanced glial activation and expression of specific CNS inflammation-related molecules in aged versus young rats following cortical stab injury. J Neuroimmunol. 2001, 119 (2): 269-277. 10.1016/S0165-5728(01)00404-0.CrossRefPubMed
40.
Sutherland GR, Dix GA, Auer RN: Effect of age in rodent models of focal and forebrain ischemia. Stroke. 1996, 27 (9): 1663-1667. 10.1161/01.STR.27.9.1663. discussion 1668CrossRefPubMed
41.
Hurley SD, Coleman PD: Facial nerve axotomy in aged and young adult rats: analysis of the glial response. Neurobiol Aging. 2003, 24 (3): 511-518. 10.1016/S0197-4580(02)00097-0.CrossRefPubMed
42.
Saville LR, Pospisil CH, Mawhinney LA, Bao F, Simedrea FC, Peters AA, O'Connell PJ, Weaver LC, Dekaban GA: A monoclonal antibody to CD11d reduces the inflammatory infiltrate into the injured spinal cord: a potential neuroprotective treatment. J Neuroimmunol. 2004, 156 (1–2): 42-57.CrossRefPubMed
43.
Fleming JC, Bao F, Chen Y, Hamilton EF, Relton JK, Weaver LC: Alpha4beta1 integrin blockade after spinal cord injury decreases damage and improves neurological function. Exp Neurol. 2008, 214 (2): 147-159. 10.1016/j.expneurol.2008.04.024.CrossRefPubMed
44.
Rapalino O, Lazarov-Spiegler O, Agranov E, Velan GJ, Yoles E, Fraidakis M, Solomon A, Gepstein R, Katz A, Belkin M, Hadani M, Schwartz M: Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nat Med. 1998, 4 (7): 814-821. 10.1038/nm0798-814.CrossRefPubMed
45.
Shechter R, Raposo C, London A, Sagi I, Schwartz M: The glial scar-monocyte interplay: a pivotal resolution phase in spinal cord repair. PLoS One. 2011, 6 (12): e27969-10.1371/journal.pone.0027969.PubMedCentralCrossRefPubMed
46.
Popovich PG, van Rooijen N, Hickey WF, Preidis G, McGaughy V: Hematogenous macrophages express CD8 and distribute to regions of lesion cavitation after spinal cord injury. Exp Neurol. 2003, 182 (2): 275-287. 10.1016/S0014-4886(03)00120-1.CrossRefPubMed
47.
Batchelor PE, Tan S, Wills TE, Porritt MJ, Howells DW: Comparison of inflammation in the brain and spinal cord following mechanical injury. J Neurotrauma. 2008, 25 (10): 1217-1225. 10.1089/neu.2007.0308.CrossRefPubMed
48.
Kigerl KA, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, Popovich PG: Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci. 2009, 29 (43): 13435-13444. 10.1523/JNEUROSCI.3257-09.2009.PubMedCentralCrossRefPubMed
49.
Ondarza AB, Ye Z, Hulsebosch CE: Direct evidence of primary afferent sprouting in distant segments following spinal cord injury in the rat: colocalization of GAP-43 and CGRP. Exp Neurol. 2003, 184 (1): 373-380. 10.1016/j.expneurol.2003.07.002.CrossRefPubMed
50.
Mills CD, Grady JJ, Hulsebosch CE: Changes in exploratory behavior as a measure of chronic central pain following spinal cord injury. J Neurotrauma. 2001, 18 (10): 1091-1105. 10.1089/08977150152693773.CrossRefPubMed
51.
Hulsebosch CE, Hains BC, Crown ED, Carlton SM: Mechanisms of chronic central neuropathic pain after spinal cord injury. Brain Res Rev. 2009, 60 (1): 202-213. 10.1016/j.brainresrev.2008.12.010.PubMedCentralCrossRefPubMed
52.
Bomstein Y, Marder JB, Vitner K, Smirnov I, Lisaey G, Butovsky O, Fulga V, Yoles E: Features of skin-coincubated macrophages that promote recovery from spinal cord injury. J Neuroimmunol. 2003, 142 (1–2): 10-16.CrossRefPubMed
53.
Swartz KR, Fee DB, Joy KM, Roberts KN, Sun S, Scheff NN, Wilson ME, Scheff SW: Gender differences in spinal cord injury are not estrogen-dependent. J Neurotrauma. 2007, 24 (3): 473-480. 10.1089/neu.2006.0167.CrossRefPubMed
54.
Yune TY, Kim SJ, Lee SM, Lee YK, Oh YJ, Kim YC, Markelonis GJ, Oh TH: Systemic administration of 17beta-estradiol reduces apoptotic cell death and improves functional recovery following traumatic spinal cord injury in rats. J Neurotrauma. 2004, 21 (3): 293-306. 10.1089/089771504322972086.CrossRefPubMed
55.
Schmitz C, Hof PR: Recommendations for straightforward and rigorous methods of counting neurons based on a computer simulation approach. J Chem Neuroanat. 2000, 20 (1): 93-114. 10.1016/S0891-0618(00)00066-1.CrossRefPubMed
56.
Dodds AW, Sim RB: Complement: A Practical Approach. 1997, Oxford; New York: IRL Press at Oxford University Press, 274-
Metadata
Title
Characterization of recovery, repair, and inflammatory processes following contusion spinal cord injury in old female rats: is age a limitation?
Authors
Mitra J Hooshmand
Manuel D Galvan
Elizabeth Partida
Aileen J Anderson
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Immunity & Ageing / Issue 1/2014
Electronic ISSN: 1742-4933
DOI
https://doi.org/10.1186/1742-4933-11-15

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