Anxiety responses and neurochemical changes in a kaolin-induced rat model of hydrocephalus

Laboratory investigation

Yong Sup Hwang Ph.D.1,3, Insop Shim Ph.D.2, and Jin Woo Chang M.D., Ph.D.1
View More View Less
  • 1 Department of Neurosurgery and Brain Research Institute, Yonsei University College of Medicine;
  • | 2 Department of Integrative Medicine, College of Medicine, Catholic University of Korea, Seoul; and
  • | 3 Institute of Interventional Medicine, M. I. Tech Co., Ltd., Pyongtaek, Korea
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $515.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $612.00
Print or Print + Online

Object

Hydrocephalus is a pathological enlargement of the ventricles of the brain, which can result from various diseases of the central nervous system. Patients with hydrocephalus frequently show motor abnormalities, such as abnormal gait and posture, as well as intellectual and emotional impairment. The present study was designed to investigate anxiety responses in rats with kaolin-induced hydrocephalus.

Methods

A total of 26 Sprague-Dawley rats were used for this study. Hydrocephalus was induced in 14 Sprague-Dawley rats by injecting 0.1 ml of 20% kaolin solution into the cisterna magna; 12 rats were administered the same volume of saline in the same fashion and served as controls. Seven of the rats that were injected with kaolin and 6 of the rats injected with saline were killed 3 days after injection (Group 1); the remaining rats were killed 4 weeks after injection (Group 2) to evaluate effects related to acute and chronic hydrocephalus. The rats were tested in an elevated plus maze after induction of hydrocephalus by kaolin injection. After the animals were killed, brain sections were immunostained for cholecystokinin and neuropeptide Y. In addition, tyrosine hydroxlyase immunoreactivity in the ventral tegmental area was evaluated by immunohistological staining.

Results

The rats with acute hydrocephalus showed decreased entry into and spent less time in the open arms of the elevated plus maze as compared with the control rats. The hydrocephalic rats had significantly more cholecystokinin-immunoreactive neurons and fewer neuropeptide Y–immunoreactive neurons in their brains. In addition, hydrocephalus progress in this model was positively correlated with the anxiety response. The numbers of tyrosine hydroxlyase–immunoreactive neurons were decreased significantly in the hydrocephalic rats as compared with the control rats.

Conclusions

These results suggest that the rat model of hydrocephalus is characterized by increased anxiety response and is associated with the functional impairment of the central dopamine system.

Abbreviations used in this paper:

CCK = cholecystokinin; NPY = neuropeptide Y; TH = tyrosine hydroxylase; VTA = ventral tegmental area.

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $515.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $612.00
  • 1

    Aigner TG, & Mishkin M: The effects of physostigmine and scopolamine on recognition memory in monkeys. Behav Neural Biol 45:8187, 1986

  • 2

    Aronin PA, & Kerrick R: Value of dynamometry in assessing upper extremity function in children with myelomeningocele. Pediatr Neurosurg 23:713, 1995

    • Search Google Scholar
    • Export Citation
  • 3

    Beninger RJ: The role of dopamine in locomotor activity and learning. Brain Res 287:173196, 1983

  • 4

    Bret P, & Chazal J: Chronic (“normal pressure”) hydrocephalus in childhood and adolescence. A review of 16 cases and reappraisal of the syndrome. Childs Nerv Syst 11:687691, 1995

    • Search Google Scholar
    • Export Citation
  • 5

    Britton KT, , Akwa Y, , Spina MG, & Koob GF: Neuropeptide Y blocks anxiogenic-like behavioral action of corticotropin-releasing factor in an operant conflict test and elevated plus maze. Peptides 21:3744, 2000

    • Search Google Scholar
    • Export Citation
  • 6

    Chang JW, , Lee BH, , Lee MS, , Chang JH, , Park YG, & Chung SS, Microelectrode recording-guided deep brain stimulation in patients with movement disorders (first trial in Korea). Kultas-Ilinsky K, & Ilinsky IA: Basal Ganglia and Thalamus in Health and Movement Disorders New York, Kluwer Academic/Plenum Publishers, 2001. 341347

    • Search Google Scholar
    • Export Citation
  • 7

    Cosan TE, , Guner AI, , Akcar N, , Uzuner K, & Tel E: Progressive ventricular enlargement in the absence of high ventricular pressure in an experimental neonatal rat model. Childs Nerv Syst 18:1014, 2002

    • Search Google Scholar
    • Export Citation
  • 8

    da Silva MC, Pathophysiology of hydrocephalus. Cinalli G, , Maixner WJ, & Sainte-Rose C: Pediatric Hydrocephalus Milan, Springer-Verlag Italia, 2004. 6577

    • Search Google Scholar
    • Export Citation
  • 9

    da Silva MC, , Drake JM, , Lemaire C, , Cross A, & Tuor UI: High-energy phosphate metabolism in a neonatal model of hydrocephalus before and after shunting. J Neurosurg 81:544553, 1994

    • Search Google Scholar
    • Export Citation
  • 10

    da Silva MC, , Michowicz S, , Drake JM, , Chumas PD, & Tuor UI: Reduced local cerebral blood flow in periventricular white matter in experimental neonatal hydrocephalus-restoration with CSF shunting. J Cereb Blood Flow Metab 15:10571065, 1995

    • Search Google Scholar
    • Export Citation
  • 11

    Dawson GR, & Tricklebank MD: Use of the elevated plus maze in the search for novel anxiolytic agents. Trends Pharmacol Sci 16:3336, 1995

    • Search Google Scholar
    • Export Citation
  • 12

    de Oliveira AR, , Reimer AE, & Brandão ML: Role of dopamine receptors in the ventral tegmental area in conditioned fear. Behav Brain Res 199:271277, 2009

    • Search Google Scholar
    • Export Citation
  • 13

    Del Bigio MR: Neuropathological changes caused by hydrocephalus. Acta Neuropathol 85:573585, 1993

  • 14

    Del Bigio MR, & Vriend JP: Monoamine neurotransmitters and amino acids in the cerebrum and striatum of immature rats with kaolin-induced hydrocephalus. Brain Res 798:119126, 1998

    • Search Google Scholar
    • Export Citation
  • 15

    File SE, Behavioural detection of anxiolytic action. Elliott JM, , Heal DJ, & Marsden CA: Experimental Approaches to Anxiety and Depression Chichester, John Wiley & Sons, 1992. 2544

    • Search Google Scholar
    • Export Citation
  • 16

    Frye CA, & Paris JJ: Infusions of bicuculline to the ventral tegmental area attenuates sexual, exploratory, and anti-anxiety behavior of proestrous rats. Pharmacol Biochem Behav 93:474481, 2009

    • Search Google Scholar
    • Export Citation
  • 17

    Groves PM: A theory of the functional organization of the neostriatum and the neostriatal control of voluntary movement. Brain Res 286:109132, 1983

    • Search Google Scholar
    • Export Citation
  • 18

    Hwang YS, , Shim I, & Chang JW: The behavioral change of locomotor activity in a kaolin-induced hydrocephalus rat model: evaluation of the effect on the dopaminergic system with progressive ventricle dilatation. Neurosci Lett 462:198202, 2009

    • Search Google Scholar
    • Export Citation
  • 19

    Ishizaki R, , Tashiro Y, , Inomoto T, & Hashimoto N: Acute and subacute hydrocephalus in a rat neonatal model: correlation with functional injury of neurotransmitter systems. Pediatr Neurosurg 33:298305, 2000

    • Search Google Scholar
    • Export Citation
  • 20

    Jang S, , Kim D, , Lee Y, , Moon S, & Oh S: Modulation of sphingosine 1-phosphate and tyrosine hydroxylase in the stress-induced anxiety. Neurochem Res 36:258267, 2011

    • Search Google Scholar
    • Export Citation
  • 21

    Kim H, , Whang WW, , Kim HT, , Pyun KH, , Cho SY, & Hahm DH, et al.: Expression of neuropeptide Y and cholecystokinin in the rat brain by chronic mild stress. Brain Res 983:201208, 2003

    • Search Google Scholar
    • Export Citation
  • 22

    Kito Y, , Kazui H, , Kubo Y, , Yoshida T, , Takaya M, & Wada T, et al.: Neuropsychiatric symptoms in patients with idiopathic normal pressure hydrocephalus. Behav Neurol 21:165174, 2009

    • Search Google Scholar
    • Export Citation
  • 23

    Laurence KM, & Coates S: Further thoughts on the natural history of hydrocephalus. Dev Med Child Neurol 4:263267, 1962

  • 24

    Lee B, , Shim I, , Lee HJ, , Yang Y, & Hahm DH: Effects of acupuncture on chronic corticosterone-induced depression-like behavior and expression of neuropeptide Y in the rats. Neurosci Lett 453:151156, 2009

    • Search Google Scholar
    • Export Citation
  • 25

    Marsden CD: Function of the basal ganglia as revealed by cognitive and motor disorders in Parkinson's disease. Can J Neurol Sci 11:1 Suppl 129135, 1984

    • Search Google Scholar
    • Export Citation
  • 26

    McAllister JP II, & Chovan P: Neonatal hydrocephalus. Mechanisms and consequences. Neurosurg Clin N Am 9:7393, 1998

  • 27

    Park HJ, , Chae Y, , Jang J, , Shim I, , Lee H, & Lim S: The effect of acupuncture on anxiety and neuropeptide Y expression in the basolateral amygdala of maternally separated rats. Neurosci Lett 377:179184, 2005

    • Search Google Scholar
    • Export Citation
  • 28

    Paxinos G, & Watson C: The Rat Brain in Stereotaxic Coordinates ed 4 San Diego, Academic Press, 1998

  • 29

    Rotzinger S, , Lovejoy DA, & Tan LA: Behavioral effects of neuropeptides in rodent models of depression and anxiety. Peptides 31:736756, 2010

    • Search Google Scholar
    • Export Citation
  • 30

    Sanberg PR, & Coyle JT: Scientific approaches to Huntington's disease. CRC Crit Rev Clin Neurobiol 1:144, 1984

  • 31

    Shim IS, , Ha Y, , Chung JY, , Lee HJ, , Yang KH, & Chang JW: Association of learning and memory impairments with changes in the septohippocampal cholinergic system in rats with kaolin-induced hydrocephalus. Neurosurgery 53:416425, 2003

    • Search Google Scholar
    • Export Citation
  • 32

    Shurtleff DB, , Foltz EL, & Loeser JD: Hydrocephalus. A definition of its progression and relationship to intellectual function, diagnosis, and complications. Am J Dis Child 125:688693, 1973

    • Search Google Scholar
    • Export Citation
  • 33

    Stanford SC, Anxiety. Webster RA: Neurotransmitters, Drugs and Brain Function Chichester, John Wiley & Sons, 2001. 395423

  • 34

    Tashiro Y, & Drake JM: Reversibility of functionally injured neurotransmitter systems with shunt placement in hydrocephalic rats: implications for intellectual impairment in hydrocephalus. J Neurosurg 88:709717, 1998

    • Search Google Scholar
    • Export Citation
  • 35

    Tashiro Y, , Drake JM, , Chakrabortty S, & Hattori T: Functional injury of cholinergic, GABAergic and dopaminergic systems in the basal ganglia of adult rat with kaolin-induced hydrocephalus. Brain Res 770:4552, 1997

    • Search Google Scholar
    • Export Citation
  • 36

    Thompson NM, , Fletcher JM, , Chapieski L, , Landry SH, , Miner ME, & Bixby J: Cognitive and motor abilities in preschool hydrocephalics. J Clin Exp Neuropsychol 13:245258, 1991

    • Search Google Scholar
    • Export Citation
  • 37

    Webster RA, Dopamine. Webster RA: Neurotransmitters, Drugs and Brain Function Chichester, John Wiley & Sons, 2001. 137161

Metrics

All Time Past Year Past 30 Days
Abstract Views 604 102 12
Full Text Views 52 4 0
PDF Downloads 43 2 0
EPUB Downloads 0 0 0