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CSF circulation and dispersion yield rapid clearance from intracranial compartments.

ABSTRACT: In this paper, we used a computational model to estimate the clearance of a tracer driven by the circulation of cerebrospinal fluid (CSF) produced in the choroid plexus (CP) located within the lateral ventricles. CSF was assumed to exit the subarachnoid space (SAS) via different outflow routes such as the parasagittal dura, cribriform plate, and/or meningeal lymphatics. We also modelled a reverse case where fluid was produced within the spinal canal and absorbed in the choroid plexus in line with observations on certain iNPH patients. No directional interstitial fluid flow was assumed within the brain parenchyma. Tracers were injected into the foramen magnum. The models demonstrate that convection in the subarachnoid space yields rapid clearance from both the SAS and the brain interstitial fluid and can speed up intracranial clearance from years, as would be the case for purely diffusive transport, to days.

SUBMITTER: Hornkjol M

PROVIDER: S-EPMC9510842 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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CSF circulation and dispersion yield rapid clearance from intracranial compartments.

Hornkjøl Martin M Valnes Lars Magnus LM Ringstad Geir G Rognes Marie E ME Eide Per-Kristian PK Mardal Kent-André KA Vinje Vegard V

Frontiers in bioengineering and biotechnology 20220912

In this paper, we used a computational model to estimate the clearance of a tracer driven by the circulation of cerebrospinal fluid (CSF) produced in the choroid plexus (CP) located within the lateral ventricles. CSF was assumed to exit the subarachnoid space (SAS) via different outflow routes such as the parasagittal dura, cribriform plate, and/or meningeal lymphatics. We also modelled a reverse case where fluid was produced within the spinal canal and absorbed in the choroid plexus in line wit ...[more]

PMID: 36172015

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Project description:BACKGROUND:Infusion testing is a common procedure to determine whether shunting will be beneficial in patients with normal pressure hydrocephalus. The method has a well-developed theoretical foundation and corresponding mathematical models that describe the CSF circulation from the choroid plexus to the arachnoid granulations. Here, we investigate to what extent the proposed glymphatic or paravascular pathway (or similar pathways) modifies the results of the traditional mathematical models. METHODS:We used a compartment model to estimate pressure in the subarachnoid space and the paravascular spaces. For the arachnoid granulations, the cribriform plate and the glymphatic circulation, resistances were calculated and used to estimate pressure and flow before and during an infusion test. Finally, different variations to the model were tested to evaluate the sensitivity of selected parameters. RESULTS:At baseline intracranial pressure (ICP), we found a very small paravascular flow directed into the subarachnoid space, while 60% of the fluid left through the arachnoid granulations and 40% left through the cribriform plate. However, during the infusion, 80% of the fluid left through the arachnoid granulations, 20% through the cribriform plate and flow in the PVS was stagnant. Resistance through the glymphatic system was computed to be 2.73 mmHg/(mL/min), considerably lower than other fluid pathways, giving non-realistic ICP during infusion if combined with a lymphatic drainage route. CONCLUSIONS:The relative distribution of CSF flow to different clearance pathways depends on ICP, with the arachnoid granulations as the main contributor to outflow. As such, ICP increase is an important factor that should be addressed when determining the pathways of injected substances in the subarachnoid space. Our results suggest that the glymphatic resistance is too high to allow for pressure driven flow by arterial pulsations and at the same time too small to allow for a direct drainage route from PVS to cervical lymphatics.

Project description:BackgroundBorrelia burgdorferi is a tick-borne spirochete that causes Lyme borreliosis (LB). After an initial tick bite, it spreads from the deposition site in the dermis to distant tissues of the host. It is generally believed that this spirochete disseminates via the hematogenous route. Borrelia persica causes relapsing fever and is able to replicate in the blood stream. Currently the exact dissemination pathway of LB pathogens in the host is not known and controversially discussed.MethodsIn this study, we established a strict intravenous infection murine model using host-adapted spirochetes. Survival capacity and infectivity of host-adapted B. burgdorferi sensu stricto (Bbss) were compared to those of B. persica (Bp) after either intradermal (ID) injection into the dorsal skin of immunocompetent mice or strict intravenous (IV) inoculation via the jugular vein. By in vitro culture and PCR, viable spirochetes and their DNA load in peripheral blood were periodically monitored during a 49/50-day course post-injection, as well as in various tissue samples collected at day 49/50. Specific antibodies in individual plasma/serum samples were detected with serological methods.ResultsRegardless of ID or IV injection, DNA of Bp was present in blood samples up to day 24 post-challenge, while no Bbss was detectable in the blood circulation during the complete observation period. In contrast to the brain tropism of Bp, Bbss spirochetes were found in ear, skin, joint, bladder, and heart tissue samples of only ID-inoculated mice. All tested tissues collected from IV-challenged mice were negative for traces of Bbss. ELISA testing of serum samples showed that Bp induced gradually increasing antibody levels after ID or IV inoculation, while Bbss did so only after ID injection but not after IV inoculation.ConclusionsThis study allows us to draw the following conclusions: (i) Bp survives in the blood and disseminates to the host's brain via the hematogenous route; and (ii) Bbss, in contrast, is cleared rapidly from the blood stream and is a tissue-bound spirochete.

Project description:BackgroundImpaired cerebrospinal fluid (CSF) homeostasis is central to the pathogenesis of idiopathic intracranial hypertension (IIH), although the precise mechanisms involved are still not completely understood. The aim of the current study was to assess the CSF/serum ratio of neurofilament light chain levels (QNfL) as a potential indicator of functional CSF outflow obstruction in IIH patients.MethodsNfL levels were measured by single molecule array in CSF and serum samples of 87 IIH patients and in three control groups, consisting of 52 multiple sclerosis (MS) patients with an acute relapse, 21 patients with an axonal polyneuropathy (PNP), and 41 neurologically healthy controls (HC). QNfL was calculated as the ratio of CSF and serum NfL levels. Similarly, we also assessed the CSF/serum ratio of glial fibrillary acidic protein (QGFAP) levels to validate the QNfL data. Routine CSF parameters including the CSF/serum albumin ratio (QAlb) were determined in all groups. Lumbar puncture opening pressure of IIH patients was measured by manometry.ResultsCSF-NfL levels (r = 0.29, p = 0.008) and QNfL (0.40, p = 0.0009), but not serum NfL (S-NfL) levels, were associated with lumbar puncture opening pressure in IIH patients. CSF-NfL levels were increased in IIH patients, MS patients, and PNP patients, whereas sNfL levels were normal in IIH, but elevated in MS and PNP. Remarkably, QNfL (p < 0.0001) as well as QGFAP (p < 0.01) were only increased in IIH patients. QNfL was positively correlated with CSF-NfL levels (r = 0.51, p = 0.0012) and negatively correlated with S-NfL levels (r = - 0.51, p = 0.0012) in HC, while it was only positively associated with CSF-NfL levels in IIH patients (r = 0.71, p < 0.0001). An increase in blood-CSF barrier permeability assessed by QAlb did not lead to a decrease in QNfL in any cohort.ConclusionsThe observed elevation of QNfL in IIH patients, which was associated with lumbar puncture opening pressure, indicates a reduced NfL transition from the CSF to serum compartment. This supports the hypothesis of a pressure-dependent CSF outflow obstruction to be critically involved in IIH pathogenesis.

Project description:Background and purposeCSF hypovolemia is a core feature of spontaneous intracranial hypotension. Spontaneous intracranial hypotension is characterized by orthostatic headache and radiologic manifestations, including CSF along the neural sleeves, diffuse pachymeningeal enhancement, and/or venous engorgement. However, these characteristics are only qualitative. Quantifying intraspinal CSF volumes could improve spontaneous intracranial hypotension diagnosis and evaluation of hypovolemic statuses in patients with spontaneous intracranial hypotension. The purpose of this study was to compare intraspinal CSF volumes across spontaneous intracranial hypotension stages and to test the clinical applicability of these measures.Materials and methodsA cohort of 23 patients with spontaneous intracranial hypotension and 32 healthy controls was subjected to brain MR imaging and MR myelography with 1.5T imaging. An automatic threshold-based segmentation method was used to calculate intraspinal CSF volumes at initial hospitalization (spontaneous intracranial hypotension-initial), partial improvement (spontaneous intracranial hypotension-intermediate), and complete recovery (spontaneous intracranial hypotension-recovery) stages.ResultsThe mean intraspinal CSF volumes observed were the following: 95.31 mL for healthy controls, 72.31 mL for spontaneous intracranial hypotension-initial, 81.15 mL for spontaneous intracranial hypotension-intermediate, and 93.74 mL for spontaneous intracranial hypotension-recovery. Increased intraspinal CSF volumes were related to disease recovery (P < .001). The intraspinal CSF volumes of patients before complete recovery were significantly lower than those of healthy controls. With the estimated intradural CSF volumes as a reference, the intraspinal CSF volume percentage was lower in patients with spontaneous intracranial hypotension with venous engorgement than in those without it (P = .058).ConclusionsWith a threshold-based segmentation method, we found that spinal CSF hypovolemia is fundamentally related to spontaneous intracranial hypotension. Intraspinal CSF volumes could be a sensitive parameter for the evaluation of treatment response and follow-up monitoring in patients with spontaneous intracranial hypotension.

Project description:Background The safety of extracranial–intracranial (EC–IC) bypass in the management of anterior circulation intracranial aneurysms (IAs) remains to be determined. This systematic review aims to summarize the existing evidence and provide guidance for the precise management of IAs. Data source We constructed search strategies and comprehensively searched Pubmed, Medline, Embase, Web of science, and Cochrane library. Methods This systematic review was actualized according to the PRISMA statement. We evaluated study quality using the methodological index for non-randomized study (MINORS). Effect sizes were pooled using a random-effects model. Heterogeneity between studies was assessed using the I2 test. Publication bias was assessed using the Egger's test. The registration number for this systematic review is CRD42023396730. Result This systematic review included a total of 21 articles, involving 915 patients. Postoperative bypass patency rate was 99% (95% CI 0.98–1.00); short-term follow-up was 98% (95% CI 0.94–1.00); long-term follow-up was 95% (95% CI 0.93–0.97). The long-term follow-up occlusion rate of saphenous vein was higher than that of radial artery (OR 6.10 95% CI 1.04–35.59). Short-term surgery-related mortality was 0.3% (95% CI 0.000–0.012); long-term follow-up was 0.4% (95% CI 0.000–0.013); The proportion of patients with a score of 0–2 on the modified Rankin Scale (mRS) during long-term follow-up was 92% (95% CI 0.86–0.98). The incidence rates of long-term follow-up complications were: ischemic 3% (95% CI 0.01–0.06); hemorrhagic 1% (95% CI 0.00–0.03); neurological deficit 1% (95% CI 0.00–0.03); other 3% (95% CI 0.01–0.06). Limitation Most of the included studies were retrospective studies. Studies reporting preoperative status were not sufficient to demonstrate postoperative improvement. Lack of sufficient subgroup information such as aneurysm rupture status. Conclusion EC–IC therapy for anterior circulation IAs has a high safety profile. Higher level of evidence is still needed to support clinical decision. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023396730, identifier: CRD42023396730.

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CSF circulation and dispersion yield rapid clearance from intracranial compartments.

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CSF circulation and dispersion yield rapid clearance from intracranial compartments.

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