AQP4 labels a subpopulation of white matter-dependent glial radial cells affected by pediatric hydrocephalus, and its expression increased in glial microvesicles released to the cerebrospinal fluid in obstructive hydrocephalus
Abstract Hydrocephalus is a distension of the ventricular system associated with ventricular zone disruption, reactive astrogliosis, periventricular white matter ischemia, axonal impairment, and corpus callosum alterations. The condition's etiology is typically attributed to a malfunction in cl...
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| Format: | Article |
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BMC
2022-03-01
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| Series: | Acta Neuropathologica Communications |
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| Online Access: | https://doi.org/10.1186/s40478-022-01345-4 |
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| author | Leandro Castañeyra-Ruiz Ibrahim González-Marrero Luis G. Hernández-Abad Emilia M. Carmona-Calero Marta R. Pardo Rebeca Baz-Davila Seunghyun Lee Michael Muhonen Ricardo Borges Agustín Castañeyra-Perdomo |
| author_facet | Leandro Castañeyra-Ruiz Ibrahim González-Marrero Luis G. Hernández-Abad Emilia M. Carmona-Calero Marta R. Pardo Rebeca Baz-Davila Seunghyun Lee Michael Muhonen Ricardo Borges Agustín Castañeyra-Perdomo |
| author_sort | Leandro Castañeyra-Ruiz |
| collection | DOAJ |
| description | Abstract Hydrocephalus is a distension of the ventricular system associated with ventricular zone disruption, reactive astrogliosis, periventricular white matter ischemia, axonal impairment, and corpus callosum alterations. The condition's etiology is typically attributed to a malfunction in classical cerebrospinal fluid (CSF) bulk flow; however, this approach does not consider the unique physiology of CSF in fetal and perinatal patients. The parenchymal fluid contributes to the glymphatic system, and plays a fundamental role in pediatric hydrocephalus, with aquaporin 4 (AQP4) as the primary facilitator of these fluid movements. Despite the importance of AQP4 in the pathophysiology of hydrocephalus, it’s expression in human fetal life is not well-studied. This manuscript systematically defines the brain expression of AQP4 in human brain development under control (n = 13) and hydrocephalic conditions (n = 3). Brains from 8 postconceptional weeks (PCW) onward and perinatal CSF from control (n = 2), obstructive (n = 6) and communicating (n = 6) hydrocephalic samples were analyzed through immunohistochemistry, immunofluorescence, western blot, and flow cytometry. Our results indicate that AQP4 expression is observed first in the archicortex, followed by the ganglionic eminences and then the neocortex. In the neocortex, it is initially at the perisylvian regions, and lastly at the occipital and prefrontal zones. Characteristic astrocyte end-feet labeling surrounding the vascular system was not established until 25 PCW. We also found AQP4 expression in a subpopulation of glial radial cells with processes that do not progress radially but, rather, curve following white matter tracts (corpus callosum and fornix), which were considered as glial stem cells (GSC). Under hydrocephalic conditions, GSC adjacent to characteristic ventricular zone disruption showed signs of early differentiation into astrocytes which may affect normal gliogenesis and contribute to the white matter dysgenesis. Finally, we found that AQP4 is expressed in the microvesicle fraction (p < 0.01) of CSF from patients with obstructive hydrocephalus. These findings suggest the potential use of AQP4 as a diagnostic and prognostic marker of pediatric hydrocephalus and as gliogenesis biomarker. |
| first_indexed | 2024-04-12T22:32:30Z |
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| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-04-12T22:32:30Z |
| publishDate | 2022-03-01 |
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| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-1f0cb4bd3b2748599437107a839a13852022-12-22T03:13:56ZengBMCActa Neuropathologica Communications2051-59602022-03-0110111910.1186/s40478-022-01345-4AQP4 labels a subpopulation of white matter-dependent glial radial cells affected by pediatric hydrocephalus, and its expression increased in glial microvesicles released to the cerebrospinal fluid in obstructive hydrocephalusLeandro Castañeyra-Ruiz0Ibrahim González-Marrero1Luis G. Hernández-Abad2Emilia M. Carmona-Calero3Marta R. Pardo4Rebeca Baz-Davila5Seunghyun Lee6Michael Muhonen7Ricardo Borges8Agustín Castañeyra-Perdomo9CHOC Children’s Research InstituteDepartamento de Ciencias Médicas Basicas, Anatomía, Facultad de Medicina, Universidad de La LagunaDepartamento de Ciencias Médicas Basicas, Anatomía, Facultad de Medicina, Universidad de La LagunaDepartamento de Ciencias Médicas Basicas, Anatomía, Facultad de Medicina, Universidad de La LagunaUnidad de Farmacologia, Facultad de Medicina, Universidad de La LagunaUnidad de Farmacologia, Facultad de Medicina, Universidad de La LagunaCHOC Children’s Research InstituteNeurosurgery Department, CHOC Children’s HospitalUnidad de Farmacologia, Facultad de Medicina, Universidad de La LagunaDepartamento de Ciencias Médicas Basicas, Anatomía, Facultad de Medicina, Universidad de La LagunaAbstract Hydrocephalus is a distension of the ventricular system associated with ventricular zone disruption, reactive astrogliosis, periventricular white matter ischemia, axonal impairment, and corpus callosum alterations. The condition's etiology is typically attributed to a malfunction in classical cerebrospinal fluid (CSF) bulk flow; however, this approach does not consider the unique physiology of CSF in fetal and perinatal patients. The parenchymal fluid contributes to the glymphatic system, and plays a fundamental role in pediatric hydrocephalus, with aquaporin 4 (AQP4) as the primary facilitator of these fluid movements. Despite the importance of AQP4 in the pathophysiology of hydrocephalus, it’s expression in human fetal life is not well-studied. This manuscript systematically defines the brain expression of AQP4 in human brain development under control (n = 13) and hydrocephalic conditions (n = 3). Brains from 8 postconceptional weeks (PCW) onward and perinatal CSF from control (n = 2), obstructive (n = 6) and communicating (n = 6) hydrocephalic samples were analyzed through immunohistochemistry, immunofluorescence, western blot, and flow cytometry. Our results indicate that AQP4 expression is observed first in the archicortex, followed by the ganglionic eminences and then the neocortex. In the neocortex, it is initially at the perisylvian regions, and lastly at the occipital and prefrontal zones. Characteristic astrocyte end-feet labeling surrounding the vascular system was not established until 25 PCW. We also found AQP4 expression in a subpopulation of glial radial cells with processes that do not progress radially but, rather, curve following white matter tracts (corpus callosum and fornix), which were considered as glial stem cells (GSC). Under hydrocephalic conditions, GSC adjacent to characteristic ventricular zone disruption showed signs of early differentiation into astrocytes which may affect normal gliogenesis and contribute to the white matter dysgenesis. Finally, we found that AQP4 is expressed in the microvesicle fraction (p < 0.01) of CSF from patients with obstructive hydrocephalus. These findings suggest the potential use of AQP4 as a diagnostic and prognostic marker of pediatric hydrocephalus and as gliogenesis biomarker.https://doi.org/10.1186/s40478-022-01345-4AQP4HydrocephalusGliogenesisGlial stem cellsReactive astrogliosisMicrovesicles |
| spellingShingle | Leandro Castañeyra-Ruiz Ibrahim González-Marrero Luis G. Hernández-Abad Emilia M. Carmona-Calero Marta R. Pardo Rebeca Baz-Davila Seunghyun Lee Michael Muhonen Ricardo Borges Agustín Castañeyra-Perdomo AQP4 labels a subpopulation of white matter-dependent glial radial cells affected by pediatric hydrocephalus, and its expression increased in glial microvesicles released to the cerebrospinal fluid in obstructive hydrocephalus Acta Neuropathologica Communications AQP4 Hydrocephalus Gliogenesis Glial stem cells Reactive astrogliosis Microvesicles |
| title | AQP4 labels a subpopulation of white matter-dependent glial radial cells affected by pediatric hydrocephalus, and its expression increased in glial microvesicles released to the cerebrospinal fluid in obstructive hydrocephalus |
| title_full | AQP4 labels a subpopulation of white matter-dependent glial radial cells affected by pediatric hydrocephalus, and its expression increased in glial microvesicles released to the cerebrospinal fluid in obstructive hydrocephalus |
| title_fullStr | AQP4 labels a subpopulation of white matter-dependent glial radial cells affected by pediatric hydrocephalus, and its expression increased in glial microvesicles released to the cerebrospinal fluid in obstructive hydrocephalus |
| title_full_unstemmed | AQP4 labels a subpopulation of white matter-dependent glial radial cells affected by pediatric hydrocephalus, and its expression increased in glial microvesicles released to the cerebrospinal fluid in obstructive hydrocephalus |
| title_short | AQP4 labels a subpopulation of white matter-dependent glial radial cells affected by pediatric hydrocephalus, and its expression increased in glial microvesicles released to the cerebrospinal fluid in obstructive hydrocephalus |
| title_sort | aqp4 labels a subpopulation of white matter dependent glial radial cells affected by pediatric hydrocephalus and its expression increased in glial microvesicles released to the cerebrospinal fluid in obstructive hydrocephalus |
| topic | AQP4 Hydrocephalus Gliogenesis Glial stem cells Reactive astrogliosis Microvesicles |
| url | https://doi.org/10.1186/s40478-022-01345-4 |
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