Early deterioration of cerebrospinal fluid dynamics in a neonatal piglet model of intraventricular hemorrhage and posthemorrhagic ventricular dilation

Laboratory investigation

Restricted access

Object

The optimal management of neonatal intraventricular hemorrhage (IVH) and posthemorrhagic ventricular dilation is challenging. The importance of early treatment has been demonstrated in a recent randomized study, involving early ventricular irrigation and drainage, which showed significant cognitive improvement at 2 years. The objective of this study was to define the changes in CSF absorption capacity over time in a neonatal piglet model of IVH.

Methods

Ten piglets (postnatal age 9–22 hours) underwent intraventricular injection of homologous blood. A ventricular access device was inserted 7–10 days later. Ventricular dilation was measured by ultrasonography. Serial constant flow infusion studies were performed through the access device from Week 2 to Week 8.

Results

Seven piglets survived long term, 43–60 days, and developed ventricular dilation; this reached a maximum by Week 6. There was no significant difference in baseline intracranial pressure throughout this period. The resistance to CSF outflow, Rout, increased from 63.5 mm Hg/ml/min in Week 2 to 118 mm Hg/ml/min in Week 4. Although Rout decreased after Week 5, the ventriculomegaly persisted.

Conclusions

In this neonatal piglet model, reduction in CSF absorptive capacity occurs early after IVH and accompanies progressive and irreversible ventriculomegaly. This suggests that early treatment of premature neonates with IVH is desirable.

Abbreviations used in this paper:DRIFT = drainage, irrigation, and fibrinolytic therapy; ICP = intracranial pressure; IQR = interquartile range; IVH = intraventricular hemorrhage; PHVD = posthemorrhagic ventricular dilation; Rout = resistance to CSF outflow; SAH = subarachnoid hemorrhage; TGF = transforming growth factor; VEGF = vascular endothelial growth factor.
Article Information

Contributor Notes

Address correspondence to: Kristian Aquilina, F.R.C.S., Department of Neurosurgery, Frenchay Hospital, Bristol BS16 1LE, England. email: K.Aquilina@bristol.ac.uk.Please include this information when citing this paper: published online September 28, 2012; DOI: 10.3171/2012.8.PEDS11386.
Headings
References
  • 1

    Aquilina KHobbs CCherian STucker APorter HWhitelaw A: A neonatal piglet model of intraventricular hemorrhage and posthemorrhagic ventricular dilation. J Neurosurg 107:2 Suppl1261362007

    • Search Google Scholar
    • Export Citation
  • 2

    Black PMTzouras AFoley L: Cerebrospinal fluid dynamics and hydrocephalus after experimental subarachnoid hemorrhage. Neurosurgery 17:57621985

    • Search Google Scholar
    • Export Citation
  • 3

    Boon AJTans JTDelwel EJEgeler-Peerdeman SMHanlo PWWurzer HA: Dutch normal-pressure hydrocephalus study: prediction of outcome after shunting by resistance to outflow of cerebrospinal fluid. J Neurosurg 87:6876931997

    • Search Google Scholar
    • Export Citation
  • 4

    Böttner MKrieglstein KUnsicker K: The transforming growth factor-betas: structure, signaling, and roles in nervous system development and functions. J Neurochem 75:222722402000

    • Search Google Scholar
    • Export Citation
  • 5

    Bradbury MWWestrop RJ: Factors influencing exit of substances from cerebrospinal fluid into deep cervical lymph of the rabbit. J Physiol 339:5195341983

    • Search Google Scholar
    • Export Citation
  • 6

    Brinker TBeck HKlinge PKischnik BOi SSamii M: Sinusoidal intrathecal infusion for assessment of CSF dynamics in kaolin-induced hydrocephalus. Acta Neurochir (Wien) 140:106910751998

    • Search Google Scholar
    • Export Citation
  • 7

    Cherian SThoresen MSilver IAWhitelaw ALove S: Transforming growth factor-betas in a rat model of neonatal posthaemorrhagic hydrocephalus. Neuropathol Appl Neurobiol 30:5856002004

    • Search Google Scholar
    • Export Citation
  • 8

    Cosan TEGuner AIAkcar NUzuner KTel E: Progressive ventricular enlargement in the absence of high ventricular pressure in an experimental neonatal rat model. Childs Nerv Syst 18:10142002

    • Search Google Scholar
    • Export Citation
  • 9

    Czosnyka MBatorski LLaniewski PMaksymowicz WKoszewski WZaworski W: A computer system for the identification of the cerebrospinal compensatory model. Acta Neurochir (Wien) 105:1121161990

    • Search Google Scholar
    • Export Citation
  • 10

    Czosnyka MWhitehouse HSmielewski PSimac SPickard JD: Testing of cerebrospinal compensatory reserve in shunted and non-shunted patients: a guide to interpretation based on an observational study. J Neurol Neurosurg Psychiatry 60:5495581996

    • Search Google Scholar
    • Export Citation
  • 11

    Czosnyka ZHCzosnyka MPickard JD: Shunt testing in-vivo: a method based on the data from the UK shunt evaluation laboratory. Acta Neurochir Suppl 81:27302002

    • Search Google Scholar
    • Export Citation
  • 12

    Davies MWSwaminathan MChuang SLBetheras FR: Reference ranges for the linear dimensions of the intracranial ventricles in preterm neonates. Arch Dis Child Fetal Neonatal Ed 82:F218F2232000

    • Search Google Scholar
    • Export Citation
  • 13

    de Vries LSLiem KDvan Dijk KSmit BJSie LRademaker KJ: Early versus late treatment of posthaemorrhagic ventricular dilatation: results of a retrospective study from five neonatal intensive care units in The Netherlands. Acta Paediatr 91:2122172002

    • Search Google Scholar
    • Export Citation
  • 14

    Donovan FMPike CJCotman CWCunningham DD: Thrombin induces apoptosis in cultured neurons and astrocytes via a pathway requiring tyrosine kinase and RhoA activities. J Neurosci 17:531653261997

    • Search Google Scholar
    • Export Citation
  • 15

    Douglas MRDaniel MLagord CAkinwunmi JJackowski ACooper C: High CSF transforming growth factor beta levels after subarachnoid haemorrhage: association with chronic communicating hydrocephalus. J Neurol Neurosurg Psychiatry 80:5455502009

    • Search Google Scholar
    • Export Citation
  • 16

    Flood CAkinwunmi JLagord CDaniel MBerry MJackowski A: Transforming growth factor-beta1 in the cerebrospinal fluid of patients with subarachnoid hemorrhage: titers derived from exogenous and endogenous sources. J Cereb Blood Flow Metab 21:1571622001

    • Search Google Scholar
    • Export Citation
  • 17

    Fox RJWalji AHMielke BPetruk KCAronyk KE: Anatomic details of intradural channels in the parasagittal dura: a possible pathway for flow of cerebrospinal fluid. Neurosurgery 39:84911996

    • Search Google Scholar
    • Export Citation
  • 18

    Fukushima NYokouchi KKawagishi KRen GHigashiyama FMoriizumi T: Proliferating cell populations in experimentally-induced hydrocephalus in developing rats. J Clin Neurosci 10:3343372003

    • Search Google Scholar
    • Export Citation
  • 19

    Gjerris FBørgesen SESørensen PSBoesen FSchmidt KHarmsen A: Resistance to cerebrospinal fluid outflow and intracranial pressure in patients with hydrocephalus after subarachnoid haemorrhage. Acta Neurochir (Wien) 88:79861987

    • Search Google Scholar
    • Export Citation
  • 20

    Gómez DGDiBenedetto ATPavese AMFirpo AHershan DBPotts DG: Development of arachnoid villi and granulations in man. Acta Anat (Basel) 111:2472581982

    • Search Google Scholar
    • Export Citation
  • 21

    Gonzalez-Darder JBarbera JCerda-Nicolas MSegura DBroseta JBarcia-Salorio JL: Sequential morphological and functional changes in kaolin-induced hydrocephalus. J Neurosurg 61:9189241984

    • Search Google Scholar
    • Export Citation
  • 22

    Grainger DJWakefield LBethell HWFarndale RWMetcalfe JC: Release and activation of platelet latent TGF-beta in blood clots during dissolution with plasmin. Nat Med 1:9329371995

    • Search Google Scholar
    • Export Citation
  • 23

    Guinane JE: Cerebrospinal fluid resistance and compliance in subacutely hydrocephalic cats. Neurology 24:1381421974

  • 24

    Heep AStoffel-Wagner BBartmann PBenseler SSchaller CGroneck P: Vascular endothelial growth factor and transforming growth factor-beta1 are highly expressed in the cerebrospinal fluid of premature infants with posthemorrhagic hydrocephalus. Pediatr Res 56:7687742004

    • Search Google Scholar
    • Export Citation
  • 25

    Hochwald GMLux WE JrSahar ARansohoff J: Experimental hydrocephalus. Changes in cerebrospinal fluid dynamics as a function of time. Arch Neurol 26:1201291972

    • Search Google Scholar
    • Export Citation
  • 26

    Hochwald GMNakamura SCamins MB: The rat in experimental obstructive hydrocephalus. Z Kinderchir 34:4034101981

  • 27

    Hochwald GMSahar ASadik ARRansohoff J: Cerebrospinal fluid production and histological observations in animals with experimental obstructive hydrocephalus. Exp Neurol 25:1901991969

    • Search Google Scholar
    • Export Citation
  • 28

    Jones HCBucknall RM: Changes in cerebrospinal fluid pressure and outflow from the lateral ventricles during development of congenital hydrocephalus in the H-Tx rat. Exp Neurol 98:5735831987

    • Search Google Scholar
    • Export Citation
  • 29

    Katzman RHussey F: A simple constant-infusion manometric test for measurement of CSF absorption. I. Rationale and method. Neurology 20:5345441970

    • Search Google Scholar
    • Export Citation
  • 30

    Khan OHEnno TLDel Bigio MR: Brain damage in neonatal rats following kaolin induction of hydrocephalus. Exp Neurol 200:3113202006

    • Search Google Scholar
    • Export Citation
  • 31

    Kida SPantazis AWeller RO: CSF drains directly from the subarachnoid space into nasal lymphatics in the rat. Anatomy, histology and immunological significance. Neuropathol Appl Neurobiol 19:4804881993

    • Search Google Scholar
    • Export Citation
  • 32

    Kim DJCzosnyka ZKeong NRadolovich DKSmielewski PSutcliffe MP: Index of cerebrospinal compensatory reserve in hydrocephalus. Neurosurgery 64:4945022009

    • Search Google Scholar
    • Export Citation
  • 33

    Kohn DFChinookoswong NChou SM: A new model of congenital hydrocephalus in the rat. Acta Neuropathol 54:2112181981

  • 34

    Kondziella DLüdemann WBrinker TSletvold OSonnewald U: Alterations in brain metabolism, CNS morphology and CSF dynamics in adult rats with kaolin-induced hydrocephalus. Brain Res 927:35412002

    • Search Google Scholar
    • Export Citation
  • 35

    Kosteljanetz M: CSF dynamics in patients with subarachnoid and/or intraventricular hemorrhage. J Neurosurg 60:9409461984

  • 36

    Kosteljanetz M: Pressure-volume conditions in patients with subarachnoid and/or intraventricular hemorrhage. J Neurosurg 63:3984031985

    • Search Google Scholar
    • Export Citation
  • 37

    Kuchiwaki HHasuo MFuruse MBrock MDietz H: [Measurement of ventricular fluid pressure and brain tissue pressure in acute experimental communicating hydrocephalus (author's transl).]. No To Shinkei 30:110911131978. (Jpn)

    • Search Google Scholar
    • Export Citation
  • 38

    Larroche JC: Post-haemorrhagic hydrocephalus in infancy. Anatomical study. Biol Neonate 20:2872991972

  • 39

    Leeds SEKong AKWise BL: Alternative pathways for drainage of cerebrospinal fluid in the canine brain. Lymphology 22:1441461989

  • 40

    Lollis SSHoopes PJKane SPaulsen KWeaver JRoberts DW: Low-dose kaolin-induced feline hydrocephalus and feline ventriculostomy: an updated model. Laboratory investigation. J Neurosurg Pediatr 4:3833882009

    • Search Google Scholar
    • Export Citation
  • 41

    Nyberg-Hansen RTorvik ABhatia R: On the pathology of experimental hydrocephalus. Brain Res 95:3433501975

  • 42

    Oi SDi Rocco C: Proposal of “evolution theory in cerebrospinal fluid dynamics” and minor pathway hydrocephalus in developing immature brain. Childs Nerv Syst 22:6626692006

    • Search Google Scholar
    • Export Citation
  • 43

    Osaka KHanda HMatsumoto SYasuda M: Development of the cerebrospinal fluid pathway in the normal and abnormal human embryos. Childs Brain 6:26381980

    • Search Google Scholar
    • Export Citation
  • 44

    Papaiconomou CBozanovic-Sosic RZakharov AJohnston M: Does neonatal cerebrospinal fluid absorption occur via arachnoid projections or extracranial lymphatics?. Am J Physiol Regul Integr Comp Physiol 283:R869R8762002

    • Search Google Scholar
    • Export Citation
  • 45

    Petrella GCzosnyka MSmielewski PAllin DGuazzo EPPickard JD: In vivo assessment of hydrocephalus shunt. Acta Neurol Scand 120:3173232009

    • Search Google Scholar
    • Export Citation
  • 46

    Sahar A: Experimental progressive hydrocephalus in the young animal. Childs Brain 5:14231979

  • 47

    Savman KNilsson UABlennow MKjellmer IWhitelaw A: Non-protein-bound iron is elevated in cerebrospinal fluid from preterm infants with posthemorrhagic ventricular dilatation. Pediatr Res 49:2082122001

    • Search Google Scholar
    • Export Citation
  • 48

    Sundström NAndersson KMarmarou AMalm JEklund A: Comparison between 3 infusion methods to measure cerebrospinal fluid outflow conductance. Clinical article. J Neurosurg 113:129413032010

    • Search Google Scholar
    • Export Citation
  • 49

    Suzuki SIshii MOttomo MIwabuchi T: Changes in the subarachnoid space after experimental subarachnoid haemorrhage in the dog: scanning electron microscopic observation. Acta Neurochir (Wien) 39:1141977

    • Search Google Scholar
    • Export Citation
  • 50

    Thoresen MHaaland KLøberg EMWhitelaw AApricena FHankø E: A piglet survival model of posthypoxic encephalopathy. Pediatr Res 40:7387481996

    • Search Google Scholar
    • Export Citation
  • 51

    Ventriculomegaly Trial Group: Randomised trial of early tapping in neonatal posthaemorrhagic ventricular dilatation. Arch Dis Child 65:1 Spec No3101990

    • Search Google Scholar
    • Export Citation
  • 52

    Ventriculomegaly Trial Group: Randomised trial of early tapping in neonatal posthaemorrhagic ventricular dilatation: results at 30 months. Arch Dis Child Fetal Neonatal Ed 70:F129F1361994

    • Search Google Scholar
    • Export Citation
  • 53

    Wagner KRSharp FRArdizzone TDLu AClark JF: Heme and iron metabolism: role in cerebral hemorrhage. J Cereb Blood Flow Metab 23:6296522003

    • Search Google Scholar
    • Export Citation
  • 54

    Whitelaw ACherian SThoresen MPople I: Posthaemorrhagic ventricular dilatation: new mechanisms and new treatment. Acta Paediatr Suppl 93:11142004

    • Search Google Scholar
    • Export Citation
  • 55

    Whitelaw AChristie SPople I: Transforming growth factorbeta1: a possible signal molecule for posthemorrhagic hydrocephalus?. Pediatr Res 46:5765801999

    • Search Google Scholar
    • Export Citation
  • 56

    Whitelaw AEvans DCarter MThoresen MWroblewska JMandera M: Randomized clinical trial of prevention of hydrocephalus after intraventricular hemorrhage in preterm infants: brain-washing versus tapping fluid. Pediatrics 119:e1071e10782007

    • Search Google Scholar
    • Export Citation
  • 57

    Whitelaw AJary SKmita GWroblewska JMusialik-Swietlinska EMandera M: Randomized trial of drainage, irrigation and fibrinolytic therapy for premature infants with posthemorrhagic ventricular dilatation: developmental outcome at 2 years. Pediatrics 125:e852e8582010

    • Search Google Scholar
    • Export Citation
  • 58

    Whitelaw AKennedy CRBrion LP: Diuretic therapy for newborn infants with posthemorrhagic ventricular dilatation. Cochrane Database Syst Rev 2CD0022702001

    • Search Google Scholar
    • Export Citation
TrendMD
Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 158 155 12
Full Text Views 86 78 1
PDF Downloads 225 161 1
EPUB Downloads 0 0 0
PubMed
Google Scholar