The Neuroepithelium Disruption Could Generate Autoantibodies against AQP4 and Cause Neuromyelitis Optica and Hydrocephalus

Abstract

Neuromyelitis optica is an inflammatory disease characterized by neuritis and myelitis of the optic nerve. Its physiopathology is connected with the aquaporin-4 water channel, since antibodies against aquaporin-4 have been found in the cerebrospinal fluid and blood of neuromyelitis optica patients. The seropositivity for aquaporin-4 antibodies is used for the diagnosis of neuromyelitis optica or neuromyelitis optica spectrum disease. On the other hand, aquaporin-4 is expressed in astrocyte feet in the brain-blood barrier and subventricular zones of the brain ventricles. Aquaporin-4 expression is high in cerebrospinal fluid in hydrocephalus. Furthermore, neuroepithelial denudation precedes noncommunicating hydrocephalus and this neuroepithelial disruption could allow aquaporin-4 to reach anomalous brain areas where it is unrecognized and induce the generation of aquaporin-4 antibodies which could cause the neuromyelitis optica and certain types of hydrocephalus.

Neuroimmune Axes of the Blood–Brain Barriers and Blood–Brain Interfaces: Bases for Physiological Regulation, Disease States, and Pharmacological Interventions

“…Autoantibodies directed at aquaporin-4, a water channel primarily located on brain ependymal cells and astrocytes, are considered the immediate cause, resulting in astrocytic activation, complement fixation, neuroinflammation with cytokine release, immune cell infiltration, and BBB disruption. Aquaporin-4 is highly expressed in ependymal cells, neuroepithelium denudation occurs in NMO, and anti-aquaporin antibodies are elevated in the CSF, all suggesting that NMO involves the choroid plexus or blood–CSF barrier ( Castaneyra-Ruiz et al, 2014 ). The antibody is an IgG that must reach the brain to induce disease and is ineffective when given peripherally unless the animals already have CNS inflammation resulting from a NMO-like picture ( Castaneyra-Ruiz et al, 2014 ).…”

“…Aquaporin-4 is highly expressed in ependymal cells, neuroepithelium denudation occurs in NMO, and anti-aquaporin antibodies are elevated in the CSF, all suggesting that NMO involves the choroid plexus or blood–CSF barrier ( Castaneyra-Ruiz et al, 2014 ). The antibody is an IgG that must reach the brain to induce disease and is ineffective when given peripherally unless the animals already have CNS inflammation resulting from a NMO-like picture ( Castaneyra-Ruiz et al, 2014 ).…”

Opportunities in posthemorrhagic hydrocephalus research: outcomes of the Hydrocephalus Association Posthemorrhagic Hydrocephalus Workshop

“…Non-surgical methods that alter CSF dynamics could be used at earlier time points in isolation or later in conjunction with temporizing devices. Current targets for these interventions include pharmaceutical reduction of CSF production by the choroid plexus (reviewed in [ 134 , 222 ]), increased CSF absorption (e.g., increase absorption through aquaporin channels [ 223 – 225 ], especially following IVH [ 226 ], as well as cranial nerve lymphatics [ 227 ]), and improved CSF flow (e.g., enhancement of natural processes that repair motile cilia). This list, however, also highlights the need for a better understanding of the choroid plexus response after IVH, alternative routes of CSF production and absorption, and the role of motile cilia in the development of hydrocephalus after hemorrhage.…”

Systemic Hypertension Effects on the Ciliary Body and Iris. An Immunofluorescence Study with Aquaporin 1, Aquaporin 4, and Na+, K+ ATPase in Hypertensive Rats

“…It has been reported that aquaporins (AQP) and Na + /K + ATPase control the rate of aqueous humor formation and are located in CB epitheliums and the iris [ 14 ]. AQP expression has been investigated in the ocular tissues of humans, mice, rats, dogs, and rabbits [ 16 , 17 ]. AQP studies suggest that AQPs are involved in regulating the water balance in ocular tissues to maintain transparency in the cornea and lens.…”