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 GLP-1R agonist exendin-4 reduces cerebrospinal fluid secretion and intracranial pressure

2017 ◽  
Author(s):  
Hannah Botfield ◽  
Maria Uldall ◽  
Connar Westgate ◽  
James Mitchell ◽  
Snorre Hagen ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Intracranial Pressure ◽  
Fluid Secretion ◽  
Cerebrospinal Fluid Secretion

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.

Papilledema

2019 ◽  
pp. 41-46
Author(s):  
Matthew J. Thurtell ◽  
Robert L. Tomsak
Keyword(s):  
Cerebrospinal Fluid ◽  
Intracranial Pressure ◽  
Fluid Secretion ◽  
Management Approach ◽  
Fluid Absorption ◽  
Increased Intracranial Pressure ◽  
Absorption Increase ◽  
Cerebrospinal Fluid Absorption ◽  
Symptoms And Signs ◽  
Cerebrospinal Fluid Secretion

Papilledema is the cardinal clinical sign of increased intracranial pressure. In this chapter, we begin by reviewing the symptoms and signs of increased intracranial pressure. We next review potential causes of increased intracranial pressure, which include intracranial masses, obstruction of the ventricular system, obstruction of cerebral venous outflow, decrease in cerebrospinal fluid absorption, increase in cerebrospinal fluid secretion, cerebral edema, medications, and idiopathic intracranial hypertension. We then review the approach to the diagnostic evaluation of increased intracranial pressure, including the recommended neuroimaging studies and cerebrospinal fluid evaluation. Lastly, we discuss the basic management approach for the patient with symptoms and signs of increased intracranial pressure.

scholarly journals Acetazolamide lowers intracranial pressure and modulates the cerebrospinal fluid secretion pathway in healthy rats

2017 ◽  
Vol 645 ◽  
pp. 33-39 ◽  
Author(s):  
Maria Uldall ◽  
Hannah Botfield ◽  
Inger Jansen-Olesen ◽  
Alexandra Sinclair ◽  
Rigmor Jensen
Keyword(s):  
Cerebrospinal Fluid ◽  
Intracranial Pressure ◽  
Fluid Secretion ◽  
Secretion Pathway ◽  
Cerebrospinal Fluid Secretion

Opinion of the Pathogenesis of the Mumps Meningites

2020 ◽  
Keyword(s):  
Cerebrospinal Fluid ◽  
Intracranial Pressure ◽  
Choroid Plexus ◽  
Present Article ◽  
Clinical Data ◽  
Fluid Secretion ◽  
Mumps Virus ◽  
Direct Involvement ◽  
Glymphatic System ◽  
Cerebrospinal Fluid Secretion

It is generally accepted that meningeal reactions in patients with mumps are due to the direct involvement of the meninges by the mumps virus. With the development of mumps vaccines, this view was extended to vaccinated people, who are considered serious post-vaccine meningitis. In present article, the author states that these reactions are not due to inflammation of the meninges, but to the choroid plexus caused by virulent and vaccine strains. Inflammation leads to an increase in cerebrospinal fluid secretion, which increases intracranial pressure and is manifested by meningeal symptoms. In the presence of this evidence, the author considers that meningeal reactions are not meningitis, but meningisms, based on clinical data, experiments on monkeys and the glymphatic system.

History, Anatomy, Histology, and Embryology of the Ventricles and Physiology of the Cerebrospinal Fluid

2021 ◽  
Author(s):  
Pinar Kuru Bektaşoğlu ◽  
Bora Gürer
Keyword(s):  
Cerebrospinal Fluid ◽  
Fluid Secretion ◽  
Colorless Liquid ◽  
Brain Ventricles ◽  
Arachnoid Granulations ◽  
Choroid Plexuses ◽  
Subarachnoid Spaces ◽  
The Mean ◽  
The Brain ◽  
Cerebrospinal Fluid Secretion

Cerebrospinal fluid is an essential, clear, and colorless liquid for the homeostasis of the brain and neuronal functioning. It circulates in the brain ventricles, the cranial and spinal subarachnoid spaces. The mean cerebrospinal fluid volume is 150 ml, with 125 ml in subarachnoid spaces and 25 ml in the ventricles. Cerebrospinal fluid is mainly secreted by the choroid plexuses. Cerebrospinal fluid secretion in adults ranges between 400 and 600 ml per day and it is renewed about four or five times a day. Cerebrospinal fluid is mainly reabsorbed from arachnoid granulations. Any disruption in this well-regulated system from overproduction to decreased absorption or obstruction could lead to hydrocephalus.

scholarly journals Cerebrospinal fluid secretion by the choroid plexus?

2016 ◽  
Vol 96 (4) ◽  
pp. 1661-1662 ◽  
Author(s):  
Darko Orešković ◽  
Milan Radoš ◽  
Marijan Klarica
Keyword(s):  
Cerebrospinal Fluid ◽  
Choroid Plexus ◽  
Fluid Secretion ◽  
Cerebrospinal Fluid Secretion

scholarly journals Radiochemical examination of transthyretin (TTR) brain penetration assisted by iododiflunisal, a TTR tetramer stabilizer and a new candidate drug for AD

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Xabier Rios ◽  
Vanessa Gómez-Vallejo ◽  
Abraham Martín ◽  
Unai Cossío ◽  
Miguel Ángel Morcillo ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Blood Brain Barrier ◽  
Mechanism Of Action ◽  
Ex Vivo ◽  
Aβ Peptide ◽  
Brain Penetration ◽  
Aβ Peptides ◽  
Candidate Drug ◽  
Aβ Aggregation

Abstract It is well settled that the amyloidogenic properties of the plasma protein transporter transthyretin (TTR) can be modulated by compounds that stabilize its native tetrameric conformation. TTR is also present in cerebrospinal fluid where it can bind to Aβ-peptides and prevent Aβ aggregation. We have previously shown that treatment of Alzheimer’s Disease (AD) model mice with iododiflunisal (IDIF), a TTR tetramer stabilizing compound, prevents AD pathologies. This evidence positioned IDIF as a new lead drug for AD. In dissecting the mechanism of action of IDIF, we disclose here different labeling strategies for the preparation of 131I-labeled IDIF and 131I- and 124I-labeled TTR, which have been further used for the preparation of IDIF-TTR complexes labeled either on the compound or the protein. The biodistribution of all labeled species after intravenous administration has been investigated in mice using ex vivo and in vivo techniques. Our results confirm the capacity of TTR to cross the blood brain barrier (BBB) and suggest that the formation of TTR-IDIF complexes enhances BBB permeability of both IDIF and TTR. The increased TTR and IDIF brain concentrations may result in higher Aβ-peptide sequestration capacity with the subsequent inhibition of AD symptoms as we have previously observed in mice.

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