title: A novel method to study cerebrospinal fluid dynamics in rats.
abstract: BACKGROUND
  Cerebrospinal fluid (CSF) flow dynamics play critical roles in both the immature and adult brain, with implications for neurodevelopment and disease processes such as hydrocephalus and neurodegeneration. Remarkably, the only reported method to date for measuring CSF formation in laboratory rats is the indirect tracer dilution method (a.k.a., ventriculocisternal perfusion), which has limitations.
  
  
  METHODS
  Anesthetized rats were mounted in a stereotaxic apparatus, both lateral ventricles were cannulated, and the Sylvian aqueduct was occluded. Fluid exited one ventricle at a rate equal to the rate of CSF formation plus the rate of infusion (if any) into the contralateral ventricle. Pharmacological agents infused at a constant known rate into the contralateral ventricle were tested for their effect on CSF formation in real-time.
  
  
  RESULTS
  The measured rate of CSF formation was increased by blockade of the Sylvian aqueduct but was not changed by increasing the outflow pressure (0-3cm of H2O). In male Wistar rats, CSF formation was age-dependent: 0.39±0.06, 0.74±0.05, 1.02±0.04 and 1.40±0.06μL/min at 8, 9, 10 and 12 weeks, respectively. CSF formation was reduced 57% by intraventricular infusion of the carbonic anhydrase inhibitor, acetazolamide.
  
  
  METHODS
  Tracer dilution methods do not permit ongoing real-time determination of the rate of CSF formation, are not readily amenable to pharmacological manipulations, and require critical assumptions. Direct measurement of CSF formation overcomes these limitations.
  
  
  CONCLUSIONS
  Direct measurement of CSF formation in rats is feasible. Our method should prove useful for studying CSF dynamics in normal physiology and disease models.
authors.affiliation: Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, United States.
authors.forename: Jason K
authors.initials: JK
authors.lastname: Karimy
authors.affiliation: Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, United States; Department of Neurosurgery, Boston Children's Hospital, Boston, MA, United States.
authors.forename: Kristopher T
authors.initials: KT
authors.lastname: Kahle
authors.affiliation: Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, United States.
authors.forename: David B
authors.initials: DB
authors.lastname: Kurland
authors.affiliation: Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, United States.
authors.forename: Edward
authors.initials: E
authors.lastname: Yu
authors.affiliation: Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, United States.
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Gerzanich
authors.affiliation: Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, United States; Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, United States; Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, United States. Electronic address: msimard@smail.umaryland.edu.
authors.forename: J Marc
authors.initials: JM
authors.lastname: Simard
mesh_terms: D000818:Animals; D002404:Catheterization / Q000379:methods*; D002535:Cerebral Aqueduct / Q000502:physiology; D002552:Cerebral Ventricles / Q000502:physiology; D002555:Cerebrospinal Fluid / Q000502:physiology*; D057446:Hydrodynamics; D008297:Male; D051381:Rats; D017208:Rats, Wistar
keywords: Acetazolamide; CSF formation; Method