Pre- and post-shunting observations in adult sheep with kaolin-induced hydrocephalus

Fluids and Barriers of the CNS

Jeff Bertrand⁴  Domenico L Di Curzio¹  Dianna Armstrong⁵  James M Drake²  Marc R Del Bigio³  Miles G Johnston⁵ 

[1] Manitoba Institute of Child Health, Winnipeg, MB, Canada;Department of Neurosurgery, Hospital for Sick Children, Toronto, ON, Canada;Department of Pathology, University of Manitoba, Winnipeg, MB, Canada;Medtronic Neurosurgery, Goleta, CA, USA;Brain Sciences, Sunnybrook Research Institute and Department of Laboratory Medicine and Pathobiology, University of Toronto, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada

关键词: Animal model;    Shunting;    Hydrocephalus;   

Others  :  806531
DOI  :  10.1186/2045-8118-10-24

 received in 2013-01-08, accepted in 2013-07-08,  发布年份 2013

【 摘 要 】

Background

The objective of this study was to examine host-shunt interactions in sheep with kaolin-induced hydrocephalus.

Methods

Forty-two sheep (29–40 kg) were utilized for this study. In 20 animals, various kaolin doses were injected into the cisterna magna including 10 and 50 mg/kg as well as 2–4 ml of a 25% kaolin suspension. Based on animal health and hydrocephalus development, 3 ml of a 25% kaolin suspension was chosen. In 16 animals, kaolin was administered and 6–8 days later, the animals received a custom made ventriculo-peritoneal shunt. In 8 animals ventricular CSF pressures were measured with a water manometer before kaolin administration and 7–8 days later. The sheep were allowed to survive for up to 9–12 weeks post-kaolin or until clinical status required euthanasia. Brains were assessed for morphological and histological changes. Ventricle/cerebrum cross sectional area ratios (V/C) were calculated from photographs of the sliced coronal planes immediately anterior to the interventricular foramina.

Results

Intraventricular pressures increased from 12.4±1.1 cm H₂O to 41.3±3.5 cm H₂O following kaolin injection (p < 0.0001, n = 8). In all animals, we observed kaolin on the basal surface of the brain and mild (V/C 0.03-0.10) to moderate (V/C >0.10) ventricular expansion. The animals lost weight between kaolin administration and shunting (33.7±1.2 kg versus 31.0±1.7 kg) with weights after shunting remaining stable up to sacrifice (31.6±2.2 kg). Of 16 shunted animals, 5 did well and were sacrificed 9–12 weeks post-kaolin. In the remainder, the study was terminated at various times due to deteriorating health. Hydrocephalus was associated with thinning of the corpus callosum, but no obvious loss of myelin staining, along with reactive astroglial (glial fibrillary acidic immunoreactive) and microglial (Iba1 immunoreactive) changes in the white matter. Ventricular shunts revealed choroid plexus ingrowth in 5/16, brain tissue ingrowth in 1/16, problems with shunt insertion in 3/16, occlusion by hemorrhagic-inflammatory material in 5/16, or no obstruction in 2/16. Free flowing CSF indicated that the peritoneal catheter was patent.

Conclusions

Cerebrospinal fluid shunts in hydrocephalic sheep fail in ways that are reminiscent of human neurosurgical experience suggesting that this model may be helpful in the development of more effective shunt technology.

【 授权许可】

   
2013 Johnston et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Low D, Drake JM, Seow WT, Ng WH: Management of ventriculo-peritoneal shunts in the paediatric population. Asian J Neurosurg 2010, 5:7-14.
• [2]Drake JM, Kestle JR, Milner R, Cinalli G, Boop F, Piatt J Jr, Haines S, Schiff SJ, Cochrane DD, Steinbok P, MacNeil N: Randomized trial of cerebrospinal fluid shunt valve design in pediatric hydrocephalus. Neurosurg 1998, 43:294-303.
• [3]Piatt JH Jr, Cosgriff M: Monte Carlo simulation of cerebrospinal fluid shunt failure and definition of instability among shunt-treated patients with hydrocephalus. J Neurosurg 2007, 107:474-478.
• [4]Drake JM, Kestle JR, Tuli S: CSF shunts 50 years on–past, present and future. Childs Nerv Syst 2000, 16:800-804.
• [5]Del Bigio MR: Biological reactions to cerebrospinal fluid shunt devices: a review of the cellular pathology. Neurosurg 1998, 42:319-325.
• [6]Harris CA, McAllister JP: 2nd: What we should know about the cellular and tissue response causing catheter obstruction in the treatment of hydrocephalus. Neurosurg 2012, 70:1589-1601.
• [7]Boulton M, Flessner M, Armstrong D, Hay J, Johnston M: Lymphatic drainage of the CNS: effects of lymphatic diversion/ligation on CSF protein transport to plasma. Am J Physiol 1997, 272:R1613-1619.
• [8]Silver I, Li B, Szalai J, Johnston M: Relationship between intracranial pressure and cervical lymphatic pressure and flow rates in sheep. Am J Physiol 1999, 277:R1712-1717.
• [9]Mollanji R, Bozanovic-Sosic R, Silver I, Li B, Kim C, Midha R, Johnston M: Intracranial pressure accommodation is impaired by blocking pathways leading to extracranial lymphatics. Am J Physiol Regul Integr Comp Physiol 2001, 280:R1573-1581.
• [10]Boulton M, Flessner M, Armstrong D, Hay J, Johnston M: Determination of volumetric cerebrospinal fluid absorption into extracranial lymphatics in sheep. Am J Physiol 1998, 274:R88-96.
• [11]Cambria S, Gambardella G, Cardia E, Cambria M, Labianca M: Experimental hydrocephalus in the fetus in utero. III. Injection of kaolin into the cisterna magna by transuterine puncture. Chir Patol Sper 1979, 27:267-272.
• [12]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, 18:331-338.
• [13]Wong J, Hemley S, Jones N, Cheng S, Bilston L, Stoodley M: Fluid outflow in a large-animal model of posttraumatic syringomyelia. Neurosurg 2012, 71:474-480.
• [14]Collins P: Experimental obstructive hydrocephalus in the rat: a scanning electron microscopic study. Neuropathol Appl Neurobiol 1979, 5:457-468.
• [15]Granholm L: Induced reversibility of ventricular dilatation in experimental hydrocephalus. Acta Neurol Scand 1966, 42:581-588.
• [16]Azzi GM, Canady AI, Ham S, Mitchell JA: Kaolin-induced hydrocephalus in the hamster: temporal sequence of changes in intracranial pressure, ventriculomegaly and whole-brain specific gravity. Acta Neuropathol 1999, 98:245-250.
• [17]Hochwald GM, Epstein F, Malhan C, Ransohoff J: The relationship of compensated to decompensated hydrocephalus in the cat. J Neurosurg 1973, 39:694-697.
• [18]Wilson CB, Bertan V: Interruption of the anterior choroidal artery in experimental hydrocephalus. Arch Neurol 1967, 17:614-619.
• [19]Yamada H, Yokota A, Haratake J, Horie A: Morphological study of experimental syringomyelia with kaolin-induced hydrocephalus in a canine model. J Neurosurg 1996, 84:999-1005.
• [20]Del Bigio MR: Future directions for therapy of childhood hydrocephalus: a view from the laboratory. Pediatr Neurosurg 2001, 34:172-181.
• [21]Slobodian I, Krassioukov-Enns D, Del Bigio MR: Protein and synthetic polymer injection for induction of obstructive hydrocephalus in rats. Cerebrospinal Fluid Res 2007, 4:9. BioMed Central Full Text
• [22]Del Bigio MR, da Silva MC, Drake JM, Tuor UI: Acute and chronic cerebral white matter damage in neonatal hydrocephalus. Can J Neurol Sci 1994, 21:299-305.
• [23]Di Curzio DL, Buist RJ, Del Bigio MR: Reduced subventricular zone proliferation and white matter damage in juvenile ferrets with kaolin-induced hydrocephalus. Exp Neurol 2013, 248C:112-128.
• [24]Del Bigio MR: Neuropathological changes caused by hydrocephalus. Acta Neuropathol 1993, 85:573-585.
• [25]Sekhar LN, Moossy J, Guthkelch AN: Malfunctioning ventriculoperitoneal shunts. Clinical and pathological features. J Neurosurg 1982, 56:411-416.
• [26]Di Trapani G, Garzetti GG, La Cara A, Pentimalli LC: Congenital hydrocephalus: a new experimental model with histopathological study. Ital J Neurol Sci 1990, 11:567-572.
• [27]Di Rocco C, Di Trapani G, Pettorossi VE, Caldarelli M: On the pathology of experimental hydrocephalus induced by artificial increase in endoventricular CSF pulse pressure. Childs Brain 1979, 5:81-95.
• [28]De Keersmaecker B, Vloeberghs M, Ville Y: Fetal hydrocephalus and intrauterine cerebral ventriculoscopy: an animal model. Fetal Diagn Ther 2005, 20:445-449.
• [29]Glick PL, Harrison MR, Halks-Miller M, Adzick NS, Nakayama DK, Anderson JH, Nyland TG, Villa R, Edwards MS: Correction of congenital hydrocephalus in utero II: Efficacy of in utero shunting. J Pediatr Surg 1984, 19:870-881.
• [30]Edwards MS, Harrison MR, Halks-Miller M, Nakayama DK, Berger MS, Glick PL, Chinn DH: Kaolin-induced congenital hydrocephalus in utero in fetal lambs and rhesus monkeys. J Neurosurg 1984, 60:115-122.
• [31]Cambria S, Gambardella G, Cardia E, Cambria M: Experimental endo-uterine hydrocephalus in foetal sheep and surgical treatment by ventriculo-amniotic shunt. Acta Neurochir (Wien) 1984, 72:235-240.
• [32]Cardoso EJ, Lachat JJ, Lopes LS, Santos AC, Colli BO: Changes caused by hydrocephalus, induced by kaolin, in the corpus callosum of adult dogs. Acta Cir Bras 2011, 26(Suppl 2):8-14.
• [33]Johnston M, Zakharov A, Papaiconomou C, Salmasi G, Armstrong D: Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species. Cerebrospinal Fluid Res 2004, 1:2. BioMed Central Full Text
• [34]Zakharov A, Papaiconomou C, Djenic J, Midha R, Johnston M: Lymphatic cerebrospinal fluid absorption pathways in neonatal sheep revealed by subarachnoid injection of Microfil. Neuropathol Appl Neurobiol 2003, 29:563-573.
• [35]Eskandari R, Packer M, Burdett EC, McAllister JP 2nd: Effect of delayed intermittent ventricular drainage on ventriculomegaly and neurological deficits in experimental neonatal hydrocephalus. Childs Nerv Syst 2012, 28:1849-1861.