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

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.

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

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.

Opinion of the Pathogenesis of the Mumps Meningites

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.

Papilledema

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.