Abstract
BackgroundMany 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.MethodsICP 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.ResultsICP 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).ConclusionsWe 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.
Highlights
Many aspects of Cerebrospinal fluid (CSF) dynamics are poorly understood due to the difficulties involved in quantification and visualization
Cerebrospinal fluid drainage pathways and time course CSF was observed to drain into the spinal canal and via the olfactory pathway, the optic nerves, and the cervical lymph nodes in all animals (Figure 2, an additional movie file shows this in more detail [see Additional file 2])
We have provided in vivo data using computed tomography (CT) imaging of CSF distribution over time, which indicates that the primary route of CSF drainage in young and aged rats is via the spinal and olfactory lymphatics, and that drainage into the sagittal sinus arachnoid granulations plays at most a minor role
Summary
Many aspects of CSF dynamics are poorly understood due to the difficulties involved in quantification and visualization. Physiological studies by Johnston’s group, suggested that the arachnoid granulations may only come into play when intracranial pressure is elevated and that lymphatic drainage routes may play a major role [26,27], especially in neonates where arachnoid granulations are sparse [28]. Both human and animal studies indicate that the spinal route, either via spinal arachnoid granulations or via lymphatics around spinal nerve root dural sheaths may be important [29,30,31,32,33,34,35]. These lymphatic routes may have important immunological significance [19]
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