Skip to main content
Top
Published in: Fluids and Barriers of the CNS 1/2007

Open Access 01-12-2007 | Research

Protein and synthetic polymer injection for induction of obstructive hydrocephalus in rats

Authors: Ili Slobodian, Dmitri Krassioukov-Enns, Marc R Del Bigio

Published in: Fluids and Barriers of the CNS | Issue 1/2007

Login to get access

Abstract

Background

The objective of this study was to develop a simple and inexpensive animal model of induced obstructive hydrocephalus with minimal tissue inflammation, as an alternative to kaolin injection.

Materials

Two-hundred and two male Sprague-Dawley rats aged 3 weeks received intracisternal injections of kaolin (25% suspension), Matrigel, type 1 collagen from rat tail, fibrin glue (Tisseel), n-butyl-cyanoacrylate (NBCA), or ethylene vinyl alcohol copolymer (Onyx-18 and Onyx-34). Magnetic resonance imaging was used to assess ventricle size. Animals were euthanized at 2, 5, 10 and 14 days post-injection for histological analysis.

Results

Kaolin was associated with 10% mortality and successful induction of hydrocephalus in 97% of survivors (ventricle area proportion 0.168 ± 0.018). Rapidly hardening agents (fibrin glue, NBCA, vinyl polymer) had high mortality rates and low success rates in survivors. Only Matrigel had relatively low mortality (17%) and moderate success rate (20%). An inflammatory response with macrophages and some lymphocytes was associated with kaolin. There was negligible inflammation associated with Matrigel. A severe inflammatory response with giant cell formation was associated with ethylene vinyl alcohol copolymer.

Conclusion

Kaolin predictably produces moderate to severe hydrocephalus with a mild chronic inflammatory reaction and fibrosis of the leptomeninges. Other synthetic polymers and biopolymers tested are unreliable and cause different types of inflammation.
Appendix
Available only for authorised users
Literature
1.
go back to reference Del Bigio MR: Neuropathological changes caused by hydrocephalus. Acta Neuropathol (Berl). 1993, 85 (6): 573-585. 10.1007/BF00334666.CrossRef Del Bigio MR: Neuropathological changes caused by hydrocephalus. Acta Neuropathol (Berl). 1993, 85 (6): 573-585. 10.1007/BF00334666.CrossRef
2.
go back to reference Del Bigio MR: Cellular damage and prevention in childhood hydrocephalus. Brain Pathol. 2004, 14 (3): 317-324.CrossRefPubMed Del Bigio MR: Cellular damage and prevention in childhood hydrocephalus. Brain Pathol. 2004, 14 (3): 317-324.CrossRefPubMed
3.
go back to reference Khan OH, Del Bigio MR: Experimental models of hydrocephalus (Chapter 26). Handbook of Experimental Neurology: Methods and Techniques in Animal Research (ISBN-10: 0521838142). Edited by: Tatlisumak T, Fisher M. 2006, Cambridge , Cambridge University Press, 457-471.CrossRef Khan OH, Del Bigio MR: Experimental models of hydrocephalus (Chapter 26). Handbook of Experimental Neurology: Methods and Techniques in Animal Research (ISBN-10: 0521838142). Edited by: Tatlisumak T, Fisher M. 2006, Cambridge , Cambridge University Press, 457-471.CrossRef
4.
go back to reference Dixon WE, Heller H: Experimentelle Hypertonie durch Eröhung des intrakaniellen Druckes. Arch Exp Pathol Pharmakol. 1932, 166: 265-275. 10.1007/BF01860670.CrossRef Dixon WE, Heller H: Experimentelle Hypertonie durch Eröhung des intrakaniellen Druckes. Arch Exp Pathol Pharmakol. 1932, 166: 265-275. 10.1007/BF01860670.CrossRef
5.
go back to reference Hochwald GM: Animal models of hydrocephalus: recent developments. Proc Soc Exp Biol Med. 1985, 178: 1-11.CrossRefPubMed Hochwald GM: Animal models of hydrocephalus: recent developments. Proc Soc Exp Biol Med. 1985, 178: 1-11.CrossRefPubMed
6.
go back to reference Nakayama DK, Harrison MR, Berger MS, Chinn DH, Halks-Miller M, Edwards MS: Correction of congenital hydrocephalus in utero I. The model: intracisternal kaolin produces hydrocephalus in fetal lambs and rhesus monkeys. J Pediatr Surg. 1983, 18 (4): 331-338. 10.1016/S0022-3468(83)80177-8.CrossRefPubMed Nakayama DK, Harrison MR, Berger MS, Chinn DH, Halks-Miller M, Edwards MS: Correction of congenital hydrocephalus in utero I. The model: intracisternal kaolin produces hydrocephalus in fetal lambs and rhesus monkeys. J Pediatr Surg. 1983, 18 (4): 331-338. 10.1016/S0022-3468(83)80177-8.CrossRefPubMed
7.
go back to reference Shinoda M, Olson L: Immunological aspects of kaolin-induced hydrocephalus. Int J Neurosci. 1997, 92 (1-2): 9-28.CrossRefPubMed Shinoda M, Olson L: Immunological aspects of kaolin-induced hydrocephalus. Int J Neurosci. 1997, 92 (1-2): 9-28.CrossRefPubMed
8.
go back to reference Del Bigio MR, Zhang YW: Cell death, axonal damage, and cell birth in the immature rat brain following induction of hydrocephalus. Exp Neurol. 1998, 154 (1): 157-169. 10.1006/exnr.1998.6922.CrossRefPubMed Del Bigio MR, Zhang YW: Cell death, axonal damage, and cell birth in the immature rat brain following induction of hydrocephalus. Exp Neurol. 1998, 154 (1): 157-169. 10.1006/exnr.1998.6922.CrossRefPubMed
9.
go back to reference Khan OH, Enno TL, Del Bigio MR: Brain damage in neonatal rats following kaolin induction of hydrocephalus. Exp Neurol. 2006, 200 (2): 311-320. 10.1016/j.expneurol.2006.02.113.CrossRefPubMed Khan OH, Enno TL, Del Bigio MR: Brain damage in neonatal rats following kaolin induction of hydrocephalus. Exp Neurol. 2006, 200 (2): 311-320. 10.1016/j.expneurol.2006.02.113.CrossRefPubMed
10.
go back to reference Cherian SS, Love S, Silver IA, Porter HJ, Whitelaw AG, Thoresen M: Posthemorrhagic ventricular dilation in the neonate: development and characterization of a rat model. J Neuropathol Exp Neurol. 2003, 62 (3): 292-303.PubMed Cherian SS, Love S, Silver IA, Porter HJ, Whitelaw AG, Thoresen M: Posthemorrhagic ventricular dilation in the neonate: development and characterization of a rat model. J Neuropathol Exp Neurol. 2003, 62 (3): 292-303.PubMed
11.
go back to reference Ohmiya M, Fukumitsu H, Nitta A, Nomoto H, Furukawa Y, Furukawa S: Administration of FGF-2 to embryonic mouse brain induces hydrocephalic brain morphology and aberrant differentiation of neurons in the postnatal cerebral cortex. J Neurosci Res. 2001, 65 (3): 228-235. 10.1002/jnr.1146.CrossRefPubMed Ohmiya M, Fukumitsu H, Nitta A, Nomoto H, Furukawa Y, Furukawa S: Administration of FGF-2 to embryonic mouse brain induces hydrocephalic brain morphology and aberrant differentiation of neurons in the postnatal cerebral cortex. J Neurosci Res. 2001, 65 (3): 228-235. 10.1002/jnr.1146.CrossRefPubMed
12.
go back to reference Johanson CE, Szmydynger Chodobska J, Chodobski A, Baird A, McMillan P, Stopa EG: Altered formation and bulk absorption of cerebrospinal fluid in FGF-2-induced hydrocephalus. Am J Physiol. 1999, 277 (1): R263-R271.PubMed Johanson CE, Szmydynger Chodobska J, Chodobski A, Baird A, McMillan P, Stopa EG: Altered formation and bulk absorption of cerebrospinal fluid in FGF-2-induced hydrocephalus. Am J Physiol. 1999, 277 (1): R263-R271.PubMed
13.
go back to reference Nakazato F, Tada T, Sekiguchi Y, Murakami K, Yanagisawa S, Tanaka Y, Hongo K: Disturbed spatial learning of rats after intraventricular administration of transforming growth factor-beta 1. Neurol Med Chir (Tokyo). 2002, 42 (4): 151-156. 10.2176/nmc.42.151.CrossRef Nakazato F, Tada T, Sekiguchi Y, Murakami K, Yanagisawa S, Tanaka Y, Hongo K: Disturbed spatial learning of rats after intraventricular administration of transforming growth factor-beta 1. Neurol Med Chir (Tokyo). 2002, 42 (4): 151-156. 10.2176/nmc.42.151.CrossRef
14.
go back to reference Tada T, Kanaji M, Kobayashi S: Induction of communicating hydrocephalus in mice by intrathecal injection of human recombinant transforming growth factor-beta 1. J Neuroimmunol. 1994, 50 (2): 153-158. 10.1016/0165-5728(94)90041-8.CrossRefPubMed Tada T, Kanaji M, Kobayashi S: Induction of communicating hydrocephalus in mice by intrathecal injection of human recombinant transforming growth factor-beta 1. J Neuroimmunol. 1994, 50 (2): 153-158. 10.1016/0165-5728(94)90041-8.CrossRefPubMed
15.
go back to reference Emonard H, Grimaud JA, Nusgens B, Lapiere CM, Foidart JM: Reconstituted basement-membrane matrix modulates fibroblast activities in vitro. J Cell Physiol. 1987, 133 (1): 95-102. 10.1002/jcp.1041330112.CrossRefPubMed Emonard H, Grimaud JA, Nusgens B, Lapiere CM, Foidart JM: Reconstituted basement-membrane matrix modulates fibroblast activities in vitro. J Cell Physiol. 1987, 133 (1): 95-102. 10.1002/jcp.1041330112.CrossRefPubMed
16.
go back to reference Kleinman HK, Martin GR: Matrigel: basement membrane matrix with biological activity. Semin Cancer Biol. 2005, 15 (5): 378-386. 10.1016/j.semcancer.2005.05.004.CrossRefPubMed Kleinman HK, Martin GR: Matrigel: basement membrane matrix with biological activity. Semin Cancer Biol. 2005, 15 (5): 378-386. 10.1016/j.semcancer.2005.05.004.CrossRefPubMed
17.
go back to reference Joosten EA, Bar PR, Gispen WH: Collagen implants and cortico-spinal axonal growth after mid-thoracic spinal cord lesion in the adult rat. J Neurosci Res. 1995, 41 (4): 481-490. 10.1002/jnr.490410407.CrossRefPubMed Joosten EA, Bar PR, Gispen WH: Collagen implants and cortico-spinal axonal growth after mid-thoracic spinal cord lesion in the adult rat. J Neurosci Res. 1995, 41 (4): 481-490. 10.1002/jnr.490410407.CrossRefPubMed
18.
go back to reference Kassam A, Horowitz M, Carrau R, Snyderman C, Welch W, Hirsch B, Chang YF: Use of Tisseel fibrin sealant in neurosurgical procedures: incidence of cerebrospinal fluid leaks and cost-benefit analysis in a retrospective study. Neurosurgery. 2003, 52 (5): 1102-1105. 10.1227/01.NEU.0000057699.37541.76.CrossRefPubMed Kassam A, Horowitz M, Carrau R, Snyderman C, Welch W, Hirsch B, Chang YF: Use of Tisseel fibrin sealant in neurosurgical procedures: incidence of cerebrospinal fluid leaks and cost-benefit analysis in a retrospective study. Neurosurgery. 2003, 52 (5): 1102-1105. 10.1227/01.NEU.0000057699.37541.76.CrossRefPubMed
19.
go back to reference Buchta C, Hedrich HC, Macher M, Hocker P, Redl H: Biochemical characterization of autologous fibrin sealants produced by CryoSeal and Vivostat in comparison to the homologous fibrin sealant product Tissucol/Tisseel. Biomaterials. 2005, 26 (31): 6233-6241. 10.1016/j.biomaterials.2005.04.014.CrossRefPubMed Buchta C, Hedrich HC, Macher M, Hocker P, Redl H: Biochemical characterization of autologous fibrin sealants produced by CryoSeal and Vivostat in comparison to the homologous fibrin sealant product Tissucol/Tisseel. Biomaterials. 2005, 26 (31): 6233-6241. 10.1016/j.biomaterials.2005.04.014.CrossRefPubMed
20.
go back to reference Weisman RA, Torsiglieri AJ, Schreiber AD, Epstein GH: Biochemical characterization of autologous fibrinogen adhesive. Laryngoscope. 1987, 97 (10): 1186-1190. 10.1288/00005537-198710000-00013.CrossRefPubMed Weisman RA, Torsiglieri AJ, Schreiber AD, Epstein GH: Biochemical characterization of autologous fibrinogen adhesive. Laryngoscope. 1987, 97 (10): 1186-1190. 10.1288/00005537-198710000-00013.CrossRefPubMed
21.
go back to reference Brothers MF, Kaufmann JC, Fox AJ, Deveikis JP: n-Butyl 2-cyanoacrylate--substitute for IBCA in interventional neuroradiology: histopathologic and polymerization time studies. AJNR Am J Neuroradiol. 1989, 10 (4): 777-786.PubMed Brothers MF, Kaufmann JC, Fox AJ, Deveikis JP: n-Butyl 2-cyanoacrylate--substitute for IBCA in interventional neuroradiology: histopathologic and polymerization time studies. AJNR Am J Neuroradiol. 1989, 10 (4): 777-786.PubMed
22.
go back to reference Johnson MJ, Ayzman I, Wood AS, Tkach JA, Klauschie J, Skarupa DJ, McAllister JP, Luciano MG: Development and characterization of an adult model of obstructive hydrocephalus. J Neurosci Meth. 1999, 91 (1-2): 55-65. 10.1016/S0165-0270(99)00072-2.CrossRef Johnson MJ, Ayzman I, Wood AS, Tkach JA, Klauschie J, Skarupa DJ, McAllister JP, Luciano MG: Development and characterization of an adult model of obstructive hydrocephalus. J Neurosci Meth. 1999, 91 (1-2): 55-65. 10.1016/S0165-0270(99)00072-2.CrossRef
23.
go back to reference Ayad M, Eskioglu E, Mericle RA: Onyx: a unique neuroembolic agent. Expert Rev Med Devices. 2006, 3 (6): 705-715. 10.1586/17434440.3.6.705.CrossRefPubMed Ayad M, Eskioglu E, Mericle RA: Onyx: a unique neuroembolic agent. Expert Rev Med Devices. 2006, 3 (6): 705-715. 10.1586/17434440.3.6.705.CrossRefPubMed
24.
go back to reference Del Bigio MR, Crook CR, Buist R: Magnetic resonance imaging and behavioral analysis of immature rats with kaolin-induced hydrocephalus: pre- and postshunting observations. Exp Neurol. 1997, 148 (1): 256-264. 10.1006/exnr.1997.6644.CrossRefPubMed Del Bigio MR, Crook CR, Buist R: Magnetic resonance imaging and behavioral analysis of immature rats with kaolin-induced hydrocephalus: pre- and postshunting observations. Exp Neurol. 1997, 148 (1): 256-264. 10.1006/exnr.1997.6644.CrossRefPubMed
25.
go back to reference Huang NF, Yu J, Sievers R, Li S, Lee RJ: Injectable biopolymers enhance angiogenesis after myocardial infarction. Tissue Eng. 2005, 11 (11-12): 1860-1866. 10.1089/ten.2005.11.1860.CrossRefPubMed Huang NF, Yu J, Sievers R, Li S, Lee RJ: Injectable biopolymers enhance angiogenesis after myocardial infarction. Tissue Eng. 2005, 11 (11-12): 1860-1866. 10.1089/ten.2005.11.1860.CrossRefPubMed
26.
go back to reference Menovsky T, de Vries J, van den Bergh Weerman M, Grotenhuis JA: Stability of fibrin sealant in cerebrospinal fluid: an in vitro study. Neurosurgery. 2002, 51 (6): 1453-1456. 10.1097/00006123-200212000-00016.PubMed Menovsky T, de Vries J, van den Bergh Weerman M, Grotenhuis JA: Stability of fibrin sealant in cerebrospinal fluid: an in vitro study. Neurosurgery. 2002, 51 (6): 1453-1456. 10.1097/00006123-200212000-00016.PubMed
27.
go back to reference de Vries J, Menovsky T, van Gulik S, Wesseling P: Histological effects of fibrin glue on nervous tissue: a safety study in rats. Surg Neurol. 2002, 57 (6): 415-422. 10.1016/S0090-3019(02)00736-X.CrossRefPubMed de Vries J, Menovsky T, van Gulik S, Wesseling P: Histological effects of fibrin glue on nervous tissue: a safety study in rats. Surg Neurol. 2002, 57 (6): 415-422. 10.1016/S0090-3019(02)00736-X.CrossRefPubMed
28.
go back to reference Terasaka S, Iwasaki Y, Shinya N, Uchida T: Fibrin glue and polyglycolic Acid nonwoven fabric as a biocompatible dural substitute. Neurosurgery. 2006, 58 (1 Suppl): ONS134-139.PubMed Terasaka S, Iwasaki Y, Shinya N, Uchida T: Fibrin glue and polyglycolic Acid nonwoven fabric as a biocompatible dural substitute. Neurosurgery. 2006, 58 (1 Suppl): ONS134-139.PubMed
29.
go back to reference Agarwal A, Varma A, Sarkar C: Histopathological changes following the use of biological and synthetic glue for dural grafts: an experimental study. Br J Neurosurg. 1998, 12 (3): 213-216. 10.1080/02688699845014.CrossRefPubMed Agarwal A, Varma A, Sarkar C: Histopathological changes following the use of biological and synthetic glue for dural grafts: an experimental study. Br J Neurosurg. 1998, 12 (3): 213-216. 10.1080/02688699845014.CrossRefPubMed
30.
go back to reference Duffner F, Ritz R, Bornemann A, Freudenstein D, Wiendl H, Siekmann R: Combined therapy of cerebral arteriovenous malformations: histological differences between a non-adhesive liquid embolic agent and n butyl 2-cyanoacrylate (NBCA). Clin Neuropathol. 2002, 21 (1): 13-17.PubMed Duffner F, Ritz R, Bornemann A, Freudenstein D, Wiendl H, Siekmann R: Combined therapy of cerebral arteriovenous malformations: histological differences between a non-adhesive liquid embolic agent and n butyl 2-cyanoacrylate (NBCA). Clin Neuropathol. 2002, 21 (1): 13-17.PubMed
31.
go back to reference Germano IM, Davis RL, Wilson CB, Hieshima GB: Histopathological follow-up study of 66 cerebral arteriovenous malformations after therapeutic embolization with polyvinyl alcohol. J Neurosurg. 1992, 76 (4): 607-614.CrossRefPubMed Germano IM, Davis RL, Wilson CB, Hieshima GB: Histopathological follow-up study of 66 cerebral arteriovenous malformations after therapeutic embolization with polyvinyl alcohol. J Neurosurg. 1992, 76 (4): 607-614.CrossRefPubMed
32.
go back to reference Quisling RG, Mickle JP, Ballinger WB, Carver CC, Kaplan B: Histopathologic analysis of intraarterial polyvinyl alcohol microemboli in rat cerebral cortex. AJNR Am J Neuroradiol. 1984, 5 (1): 101-104.PubMed Quisling RG, Mickle JP, Ballinger WB, Carver CC, Kaplan B: Histopathologic analysis of intraarterial polyvinyl alcohol microemboli in rat cerebral cortex. AJNR Am J Neuroradiol. 1984, 5 (1): 101-104.PubMed
33.
go back to reference Murayama Y, Vinuela F, Ulhoa A, Akiba Y, Duckwiler GR, Gobin YP, Vinters HV, Greff RJ: Nonadhesive liquid embolic agent for cerebral arteriovenous malformations: preliminary histopathological studies in swine rete mirabile. Neurosurgery. 1998, 43 (5): 1164-1175. 10.1097/00006123-199811000-00081.CrossRefPubMed Murayama Y, Vinuela F, Ulhoa A, Akiba Y, Duckwiler GR, Gobin YP, Vinters HV, Greff RJ: Nonadhesive liquid embolic agent for cerebral arteriovenous malformations: preliminary histopathological studies in swine rete mirabile. Neurosurgery. 1998, 43 (5): 1164-1175. 10.1097/00006123-199811000-00081.CrossRefPubMed
34.
go back to reference Santos NC, Figueira-Coelho J, Martins-Silva J, Saldanha C: Multidisciplinary utilization of dimethyl sulfoxide: pharmacological, cellular, and molecular aspects. Biochem Pharmacol. 2003, 65 (7): 1035-1041. 10.1016/S0006-2952(03)00002-9.CrossRefPubMed Santos NC, Figueira-Coelho J, Martins-Silva J, Saldanha C: Multidisciplinary utilization of dimethyl sulfoxide: pharmacological, cellular, and molecular aspects. Biochem Pharmacol. 2003, 65 (7): 1035-1041. 10.1016/S0006-2952(03)00002-9.CrossRefPubMed
Metadata
Title
Protein and synthetic polymer injection for induction of obstructive hydrocephalus in rats
Authors
Ili Slobodian
Dmitri Krassioukov-Enns
Marc R Del Bigio
Publication date
01-12-2007
Publisher
BioMed Central
Published in
Fluids and Barriers of the CNS / Issue 1/2007
Electronic ISSN: 2045-8118
DOI
https://doi.org/10.1186/1743-8454-4-9

Other articles of this Issue 1/2007

Fluids and Barriers of the CNS 1/2007 Go to the issue