title: Cerebrospinal fluid is drained primarily via the spinal canal and olfactory route in young and aged spontaneously hypertensive rats.
abstract: BACKGROUND
  Many aspects of CSF dynamics are poorly understood due to the difficulties involved in quantification and visualization. In particular, there is debate surrounding the route of CSF drainage. Our aim was to quantify CSF flow, volume, and drainage route dynamics in vivo in young and aged spontaneously hypertensive rats (SHR) using a novel contrast-enhanced computed tomography (CT) method.
  
  
  METHODS
  ICP was recorded in young (2-5 months) and aged (16 months) SHR. Contrast was administered into the lateral ventricles bilaterally and sequential CT imaging was used to visualize the entire intracranial CSF system and CSF drainage routes. A customized contrast decay software module was used to quantify CSF flow at multiple locations.
  
  
  RESULTS
  ICP was significantly higher in aged rats than in young rats (11.52 ± 2.36 mmHg, versus 7.04 ± 2.89 mmHg, p = 0.03). Contrast was observed throughout the entire intracranial CSF system and was seen to enter the spinal canal and cross the cribriform plate into the olfactory mucosa within 9.1 ± 6.1 and 22.2 ± 7.1 minutes, respectively. No contrast was observed adjacent to the sagittal sinus. There were no significant differences between young and aged rats in either contrast distribution times or CSF flow rates. Mean flow rates (combined young and aged) were 3.0 ± 1.5 μL/min at the cerebral aqueduct; 3.5 ± 1.4 μL/min at the 3rd ventricle; and 2.8 ± 0.9 μL/min at the 4th ventricle. Intracranial CSF volumes (and as percentage total brain volume) were 204 ± 97 μL (8.8 ± 4.3%) in the young and 275 ± 35 μL (10.8 ± 1.9%) in the aged animals (NS).
  
  
  CONCLUSIONS
  We have demonstrated a contrast-enhanced CT technique for measuring and visualising CSF dynamics in vivo. These results indicate substantial drainage of CSF via spinal and olfactory routes, but there was little evidence of drainage via sagittal sinus arachnoid granulations in either young or aged animals. The data suggests that spinal and olfactory routes are the primary routes of CSF drainage and that sagittal sinus arachnoid granulations play a minor role, even in aged rats with higher ICP.
authors.affiliation: University of Newcastle and Hunter Medical Research Institute, University of Newcastle: School of Biomedical Sciences & Pharmacy, Medical Sciences Building, Callaghan, NSW 2308, Australia.
authors.forename: Lucy A
authors.initials: LA
authors.lastname: Murtha
authors.affiliation: Apollo Medical Imaging Technology Pty Ltd, Suite 611, 365 Little Collins Street, Melbourne, Vic 3000, Australia.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Hunter New England Local Health District: Department of Neurology, John Hunter Hospital, Locked Bag 1, Hunter Region M.C, NSW 2310, Australia.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Parsons
authors.affiliation: Hunter New England Local Health District: Department of Neurology, John Hunter Hospital, Locked Bag 1, Hunter Region M.C, NSW 2310, Australia.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Levi
authors.affiliation: University of Newcastle and Hunter Medical Research Institute, University of Newcastle: School of Biomedical Sciences & Pharmacy, Medical Sciences Building, Callaghan, NSW 2308, Australia.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Beard
authors.affiliation: University of Newcastle and Hunter Medical Research Institute, University of Newcastle: School of Biomedical Sciences & Pharmacy, Medical Sciences Building, Callaghan, NSW 2308, Australia ; Hunter New England Local Health District: Department of Neurology, John Hunter Hospital, Locked Bag 1, Hunter Region M.C, NSW 2310, Australia.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Spratt
authors.affiliation: University of Newcastle and Hunter Medical Research Institute, University of Newcastle: School of Biomedical Sciences & Pharmacy, Medical Sciences Building, Callaghan, NSW 2308, Australia.
authors.forename: Damian D
authors.initials: DD
authors.lastname: McLeod
keywords: Age; CSF; Cerebrospinal fluid dynamics; Computed tomography; Contrast; Intracranial pressure (ICP); SHR; Spontaneously hypertensive rat