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. 2014 Jun 6;11:12.
doi: 10.1186/2045-8118-11-12. eCollection 2014.

Cerebrospinal fluid is drained primarily via the spinal canal and olfactory route in young and aged spontaneously hypertensive rats

Lucy A Murtha  1 , Qing Yang  2 , Mark W Parsons  3 , Christopher R Levi  3 , Daniel J Beard  1 , Neil J Spratt  4 , Damian D McLeod  1
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Cerebrospinal fluid is drained primarily via the spinal canal and olfactory route in young and aged spontaneously hypertensive rats

Lucy A Murtha et al. Fluids Barriers CNS. .
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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.

Keywords: Age; CSF; Cerebrospinal fluid dynamics; Computed tomography; Contrast; Intracranial pressure (ICP); SHR; Spontaneously hypertensive rat.

Figures

Figure 1
Calculating cerebrospinal fluid flow through the cerebral aqueduct of the rat. Radio-opaque contrast (20 μl) was simultaneously injected into each lateral ventricle at 2 μl/min for 10 min while plain CT images (0.6 mm slice thickness) were taken over 60 minutes. A small region-of-interest (ROI) (yellow box, arrow) was positioned within the centre of the aqueduct and the decay rate used to generate flow maps. An additional movie file shows this in more detail [see Additional file 1].
Figure 2
Figure 2
Cerebrospinal fluid (CSF) system in a rat imaged with contrast-enhanced computed tomography (CT). Images show a 3D render reconstruction of CT images after 20 μL of radio-opaque contrast was injected into each lateral ventricle via cannulae guided through hollow screws inserted into the skull. Anatomical landmarks of the CSF system in the rat are based on a stereotaxic rat atlas [61]. Basal cisterns are not depicted in the rat atlas, but their location at the base of the brain is indicated by presence of contrast enhanced CSF in this location. An additional movie file shows this in more detail [see Additional file 2].
Figure 3
Time taken for contrast-enhanced cerebrospinal fluid to reach major anatomical landmarks within the rat CSF system. Young (2–5 months); Aged (16 months). Mean ± SD.
Figure 4
Cerebrospinal fluid (CSF) dynamics in the rat. (A) Flow rate through the cerebral aqueduct; (B) Flow rate through the 3rd ventricle; (C) Flow rate through the 4th ventricle; (D) Total intracranial CSF volume, in young (2–5 months) versus aged (16 months) spontaneously hypertensive rats. Data presented as individual data points with mean ± SD.
Figure 5
Total brain volume calculated from baseline non-contrast images. Young (2–5 months); Aged (16 months). Mean ± SD.
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