scholarly journals Altered Cerebrospinal Fluid Clearance and Increased Intracranial Pressure in Rats 18 h After Experimental Cortical Ischaemia

2021 ◽  
Vol 14 ◽  
Author(s):  
Steven W. Bothwell ◽  
Daniel Omileke ◽  
Rebecca J. Hood ◽  
Debbie-Gai Pepperall ◽  
Sara Azarpeykan ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Intracranial Pressure ◽  
Lymph Nodes ◽  
Subarachnoid Space ◽  
Ex Vivo ◽  
Bimodal Distribution ◽  
Cervical Lymph Nodes ◽  
Post Stroke ◽  
Spinal Subarachnoid Space

Oedema-independent intracranial pressure (ICP) rise peaks 20–22-h post-stroke in rats and may explain early neurological deterioration. Cerebrospinal fluid (CSF) volume changes may be involved. Cranial CSF clearance primarily occurs via the cervical lymphatics and movement into the spinal portion of the cranio-spinal compartment. We explored whether impaired CSF clearance at these sites could explain ICP rise after stroke. We recorded ICP at baseline and 18-h post-stroke, when we expect changes contributing to peak ICP to be present. CSF clearance was assessed in rats receiving photothrombotic stroke or sham surgery by intraventricular tracer infusion. Tracer concentration was quantified in the deep cervical lymph nodes ex vivo and tracer transit to the spinal subarachnoid space was imaged in vivo. ICP rose significantly from baseline to 18-h post-stroke in stroke vs. sham rats [median = 5 mmHg, interquartile range (IQR) = 0.1–9.43, n = 12, vs. −0.3 mmHg, IQR = −1.9–1.7, n = 10], p = 0.03. There was a bimodal distribution of rats with and without ICP rise. Tracer in the deep cervical lymph nodes was significantly lower in stroke with ICP rise (0 μg/mL, IQR = 0–0.11) and without ICP rise (0 μg/mL, IQR = 0–4.47) compared with sham rats (4.17 μg/mL, IQR = 0.74–8.51), p = 0.02. ICP rise was inversely correlated with faster CSF transit to the spinal subarachnoid space (R = −0.59, p = 0.006, Spearman’s correlation). These data suggest that reduced cranial clearance of CSF via cervical lymphatics may contribute to post-stroke ICP rise, partially compensated via increased spinal CSF outflow.

scholarly journals Cerebrospinal fluid drainage kinetics across the cribriform plate are reduced with aging

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Molly Brady ◽  
Akib Rahman ◽  
Abigail Combs ◽  
Chethana Venkatraman ◽  
R. Tristan Kasper ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Cerebrospinal Fluid ◽  
Subarachnoid Space ◽  
Ex Vivo ◽  
Cribriform Plate ◽  
Cervical Lymph Nodes ◽  
Spinal Subarachnoid Space ◽  
Ex Vivo Tissues ◽  
The Brain

Abstract Background Continuous circulation and drainage of cerebrospinal fluid (CSF) are essential for the elimination of CSF-borne metabolic products and neuronal function. While multiple CSF drainage pathways have been identified, the significance of each to normal drainage and whether there are differential changes at CSF outflow regions in the aging brain are unclear. Methods Dynamic in vivo imaging of near infrared fluorescently-labeled albumin was used to simultaneously visualize the flow of CSF at outflow regions on the dorsal side (transcranial and -spinal) of the central nervous system. This was followed by kinetic analysis, which included the elimination rate constants for these regions. In addition, tracer distribution in ex vivo tissues were assessed, including the nasal/cribriform region, dorsal and ventral surfaces of the brain, spinal cord, cranial dura, skull base, optic and trigeminal nerves and cervical lymph nodes. Results Based on the in vivo data, there was evidence of CSF elimination, as determined by the rate of clearance, from the nasal route across the cribriform plate and spinal subarachnoid space, but not from the dorsal dural regions. Using ex vivo tissue samples, the presence of tracer was confirmed in the cribriform area and olfactory regions, around pial blood vessels, spinal subarachnoid space, spinal cord and cervical lymph nodes but not for the dorsal dura, skull base or the other cranial nerves. Also, ex vivo tissues showed retention of tracer along brain fissures and regions associated with cisterns on the brain surfaces, but not in the brain parenchyma. Aging reduced CSF elimination across the cribriform plate but not that from the spinal SAS nor retention on the brain surfaces. Conclusions Collectively, these data show that the main CSF outflow sites were the nasal region across the cribriform plate and from the spinal regions in mice. In young adult mice, the contribution of the nasal and cribriform route to outflow was much higher than from the spinal regions. In older mice, the contribution of the nasal route to CSF outflow was reduced significantly but not for the spinal routes. This kinetic approach may have significance in determining early changes in CSF drainage in neurological disorder, age-related cognitive decline and brain diseases.

Increased Intracranial Pressure

1981 ◽  
Vol 2 (9) ◽  
pp. 269-276
Author(s):  
John F. Griffith ◽  
Jimmy C. Brasfield
Keyword(s):  
Cerebrospinal Fluid ◽  
Intracranial Pressure ◽  
Subarachnoid Space ◽  
Buffering Capacity ◽  
Raised Intracranial Pressure ◽  
Cranial Cavity ◽  
Increased Intracranial Pressure ◽  
Underlying Process ◽  
Spinal Subarachnoid Space ◽  
Rate Of Absorption

The infant or child with increasing pressure within the cranial cavity must be identified early and treated promptly in order to prevent serious complications or death. When the pressure elevation is gradual it is frequently well tolerated, and the patient may seem deceptively well. There is a critical point, however, beyond which any further increase in pressure leads to a catastrophic deterioration in the patient's condition.1 When this occurs, the outlook for quality survival is poor despite the best therapy. Unfortunately, this can occur when the underlying process is benign and would have been reversible if recognized and treated promptly. For prompt recognition and treatment, the physician must be familiar with the pathophysiology of raised intracranial pressure. PATHOPHYSIOLOGY The intracranial compartment contains blood vessels, cerebrospinal fluid (CSF), brain, and leptomeninges which include the rigid dural membranes forming the falx and tentorium. Whenever there is an increase in the volume of any one of these intracranial components (brain, CSF, blood) there must be a corresponding reduction in the size of the others in order for the intracranial pressure to remain normal. This type of compensation or buffering capacity is particularly important in the early stages of intracranial disease. As the pressure mounts from any type of mass lesion, the CSF is displaced caudally into the spinal subarachnoid space and there is a corresponding increase in the rate of absorption of CSF.2

scholarly journals Clearance of cerebrospinal fluid from the sacral spine through lymphatic vessels

2019 ◽  
Vol 216 (11) ◽  
pp. 2492-2502 ◽  
Author(s):  
Qiaoli Ma ◽  
Yann Decker ◽  
Andreas Müller ◽  
Benjamin V. Ineichen ◽  
Steven T. Proulx
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Space ◽  
Near Infrared ◽  
Cranial Nerves ◽  
Lymphatic Vessels ◽  
Intraventricular Injection ◽  
Spinal Subarachnoid Space ◽  
Cord Injury ◽  
Sacral Spine

The pathways of circulation and clearance of cerebrospinal fluid (CSF) in the spine have yet to be elucidated. We have recently shown with dynamic in vivo imaging that routes of outflow of CSF in mice occur along cranial nerves to extracranial lymphatic vessels. Here, we use near-infrared and magnetic resonance imaging to demonstrate the flow of CSF tracers within the spinal column and reveal the major spinal pathways for outflow to lymphatic vessels in mice. We found that after intraventricular injection, a spread of CSF tracers occurs within both the central canal and the spinal subarachnoid space toward the caudal end of the spine. Outflow of CSF tracers from the spinal subarachnoid space occurred predominantly from intravertebral regions of the sacral spine to lymphatic vessels, leading to sacral and iliac LNs. Clearance of CSF from the spine to lymphatic vessels may have significance for many conditions, including multiple sclerosis and spinal cord injury.

Robot-assisted endoscopic exploration of the spinal cord

2010 ◽  
Vol 224 (7) ◽  
pp. 1515-1529 ◽  
Author(s):  
L Ascari ◽  
C Stefanini ◽  
U Bertocchi ◽  
P Dario
Keyword(s):  
Spinal Cord ◽  
Subarachnoid Space ◽  
Ex Vivo ◽  
Hierarchical Control ◽  
Three Dimensional ◽  
Robot Assisted ◽  
Actuation System ◽  
Spinal Subarachnoid Space

This work presents the design and development of an integrated image-guided robot-assisted endoscopic system for the safe navigation within the spinal subarachnoid space, providing the surgeon with the direct vision of the structures (i.e. spinal cord, roots, vessels) and the possibility of performing some particularly useful operations, like local electrostimulation of nerve roots. The modelling, micro-fabrication, fluidic sustentation, and cable-based actuation system of a steerable tip for a multilumen flexible catheter is described; the hierarchical control system shared between the surgeon and the computer, and based on machine vision techniques and a simple but effective three-dimensional reconstruction is detailed. The Blind Expected Perception sensory-motor scheme is proposed in robot-assited endoscopy. Results from in vitro, ex vivo, and in vivo experiments show that the described model can accurately predict the shape of the catheter given the tension distribution on the cables, that the proposed actuation system can assure smooth and precise control of the catheter tip, that the fluidic sustentation of the catheter is essential in in vivo navigation, and that the proposed rear view mirror interface to show non-visible obstacles is appropriate; in conclusion, the results proved the validity of the proposed solution to develop an intrinsically safe robotic system for navigation and intervention in a narrow and challenging environment such as the spinal subarachnoid space.

Noninvasive optical imaging of the subarachnoid space and cerebrospinal fluid pathways based on near-infrared fluorescence

1997 ◽  
Vol 87 (5) ◽  
pp. 738-745 ◽  
Author(s):  
Kaoru Sakatani ◽  
Masaki Kashiwasake-Jibu ◽  
Yoshinori Taka ◽  
Shijie Wang ◽  
Huancong Zuo ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Injection Site ◽  
Fluorescence Imaging ◽  
Subarachnoid Space ◽  
Near Infrared ◽  
Content Type ◽  
Spinal Subarachnoid Space ◽  
Lumbar Spinal ◽  
Fine Print

✓ The authors have developed a noninvasive optical method to image the subarachnoid space and cerebrospinal fluid pathways in vivo based on the near-infrared fluorescence of indocyanine green (ICG). The ICG was bound to purified lipoproteins (ICG—lipoprotein) and injected into the subarachnoid space of neonatal and adult rats. The ICG fluorescence was detected by a cooled charge-coupled device camera. After injection of ICG—lipoprotein into the cerebral subarachnoid space of the neonatal rat, ICG fluorescence was clearly detected at the injection site through the skull and skin. The ICG fluorescence was observed in the cerebellum and the lumbar spinal cord 1 and 8 hours postinjection, respectively. After injection of ICG—lipoprotein into the lumbar spinal subarachnoid space of an adult rat, ICG fluorescence was observed from the injection site to the thoracic levels along the spinal subarachnoid space. In addition, with the rat's head tilted downward, ICG fluorescence had extended to the cerebral subarachnoid space by 1 hour postinjection. The ICG fluorescence imaging of the cerebral subarachnoid space demonstrated an increase in fluorescence intensity around the lambdoid suture and the forebrain. On dissection of the rat brain the former location was identified as the supracerebellar cistern and the latter as the olfactory cistern. The results of this study are the first to demonstrate that an optical technique is applicable to imaging of the subarachnoid space and cerebrospinal fluid pathways in vivo. In addition, ICG—lipoprotein provides a sensitive optical tracer for imaging extravascular biological structures. Finally, ICG fluorescence imaging does not require an intricate imaging system because ICG is localized near the surface of the body.

scholarly journals Acetazolamide modulates intracranial pressure directly by its action on the cerebrospinal fluid secretion apparatus

2022 ◽  
Author(s):  
Dagne Barbuskaite ◽  
Eva Kjer Oernbo ◽  
Jonathan Henry Wardman ◽  
Trine Lisberg Toft-Bertelsen ◽  
Eller Conti ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Intracranial Pressure ◽  
Ex Vivo ◽  
Direct Action ◽  
Fluid Secretion ◽  
Carbonic Anhydrases ◽  
Patient Groups ◽  
Systemic Side Effects ◽  
Cerebrospinal Fluid Secretion

Elevated intracranial pressure (ICP) is observed in many neurological pathologies, e.g. hydrocephalus and stroke. This condition is routinely relieved with neurosurgical approaches, since effective and targeted pharmacological tools are still lacking. The carbonic anhydrase inhibitor, acetazolamide (AZE), may be employed to treat elevated ICP. However, its effectiveness is questioned, its location of action unresolved, and its tolerability low. Here, we employed in vivo and ex vivo approaches to reveal the efficacy and mode of action of AZE in the rat brain. The drug effectively reduced the ICP, irrespective of the mode of drug administration and level of anaesthesia. The effect occurred via a direct action on the choroid plexus and an associated decrease in cerebrospinal fluid secretion, and not indirectly via the systemic action of AZE on renal and vascular processes. Upon a single administration, the reduced ICP endured for approximately 10 h post-AZE delivery with no long-term changes of brain water content or choroidal transporter expression. However, a persistent reduction of ICP was secured with repeated AZE administrations throughout the day. Future specific targeting of choroidal carbonic anhydrases may limit the systemic side effects, and therefore enhance the treatment tolerability and effectiveness in select patient groups experiencing elevated ICP.

The perivascular pathways for influx of cerebrospinal fluid are most efficient in the midbrain

2017 ◽  
Vol 131 (22) ◽  
pp. 2745-2752 ◽  
Author(s):  
Howard Dobson ◽  
Matthew MacGregor Sharp ◽  
Richard Cumpsty ◽  
Theodore P. Criswell ◽  
Tyler Wellman ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Cerebrospinal Fluid ◽  
Subarachnoid Space ◽  
Lymphatic Vessels ◽  
Brain Parenchyma ◽  
Basement Membranes ◽  
Post Mortem ◽  
Cervical Lymph Nodes ◽  
The Brain

Although there are no conventional lymphatic vessels in the brain, fluid and solutes drain along basement membranes (BMs) of cerebral capillaries and arteries towards the subarachnoid space and cervical lymph nodes. Convective influx/glymphatic entry of the cerebrospinal fluid (CSF) into the brain parenchyma occurs along the pial-glial BMs of arteries. This project tested the hypotheses that pial-glial BM of arteries are thicker in the midbrain, allowing more glymphatic entry of CSF. The in vivo MRI and PET images were obtained from a 4.2-year-old dog, whereas the post-mortem electron microscopy was performed in a 12-year-old dog. We demonstrated a significant increase in the thickness of the pial-glial BM in the midbrain compared with the same BM in different regions of the brain and an increase in the convective influx of fluid from the subarachnoid space. These results are highly significant for the intrathecal drug delivery into the brain, indicating that the midbrain is better equipped for convective influx/glymphatic entry of the CSF.

scholarly journals Spinal cerebrospinal fluid flow is increased in rats with elevated intracranial pressure 18 hours after cortical ischaemic stroke

2020 ◽  
Author(s):  
Steven William Bothwell ◽  
Daniel Omileke ◽  
Debbie-Gai Pepperall ◽  
Adjanie Patabendige ◽  
Neil J Spratt
Keyword(s):  
Cerebrospinal Fluid ◽  
Intracranial Pressure ◽  
Infarct Volume ◽  
Compensatory Mechanism ◽  
Tracer Transport ◽  
Cerebrospinal Fluid Flow ◽  
Post Stroke ◽  
Spinal Subarachnoid Space ◽  
Infarct Expansion ◽  
Underlying Mechanisms

Abstract Background A dramatic oedema-independent intracranial pressure (ICP) rise occurs 24 hours post-stroke in rats and may explain infarct expansion. Underlying mechanisms of this rise are unknown but evidence suggests cerebrospinal fluid (CSF) dynamics are involved. Methods We investigated how CSF flow changes post-stroke and how this relates to ICP by infusing CSF tracer into the lateral ventricles of rats and assessing transport time and total tracer transport to the spinal subarachnoid space over a 90 minute period. Results Stroke animals with ICP rise had faster tracer transit when compared with stroke animals without ICP rise (27.6 ± 4, n = 6, vs 48.6 ± 4.5 mins, n = 6) or animals subjected to a sham procedure (47.9 ± 4 mins, n = 8), F(2,17) = 0.1, p≤0.01. There was a correlation between tracer transit time and ΔICP (R = -0.52, p=0.02) and infarct volume (R = -0.6, p=0.04). There was no difference in total tracer observed. Conclusions Faster tracer transit in stroke animals may be explained by impairment of other CSF outflow pathways, whereby, spinal drainage acts as a compensatory mechanism. Investigation into the disruption of other CSF drainage routes post-stroke may offer insight into the underlying mechanisms of infarct expansion post-stroke.

A Coupled Simulation of Spinal Cord Blood Flow and Cerebrospinal Fluid Motion in the Spinal Subarachnoid Space Based on In Vivo Measurements

2011 ◽  
Author(s):  
Bryn Martin ◽  
Philippe Reymond ◽  
Olivier Balédent ◽  
Jan Novy ◽  
Nikos Stergiopulos
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Cerebrospinal Fluid ◽  
Subarachnoid Space ◽  
Tree Model ◽  
Arterial Tree ◽  
In Vivo Measurements ◽  
Spinal Subarachnoid Space ◽  
Systemic Arterial Tree

A preliminary coupled 1-D model of the systemic arterial tree and cerebrospinal fluid (CSF) system was constructed. The systemic tree model includes arteries greater than 2 mm in diameter and a simplified spinal cord vasculature. Coupling of the arterial tree and CSF system is accomplished by a transfer function based on in vivo cerebral blood flow (CBF) and CSF pulsation measurements in 17 young healthy adults. A 1-D tube model of the CSF in the spinal subarachnoid space (SSS) is formed based on in vivo measurements and used to determine flow and pressure along the SSS. The pressure and flow results in the CSF and systemic arterial tree are qualitatively and quantitatively similar to in vivo measurements in healthy subjects. The relative arrival time of blood pulsations in the spinal cord and CSF in the SSS is impacted by CSF system compliance and geometry. With low CSF system compliance the CSF pulsations arrive around the spinal cord before arterial pulsations and vice versa. Overall, the preliminary results support that geometric and mechanical properties of the CSF and cardiovascular system have an important impact on the flow and pressure environment and accent the importance to obtain in vivo measurements to improve modeling capabilities.

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