Congenital Hydrocephalus

Furey, Charuta G.; Antwi, Prince; Kahle, Kristopher T.

doi:10.1007/978-3-319-97928-1_5

Cited by 4 publications

(4 citation statements)

References 190 publications

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“…2 Instituto de Investigación Biomédica de Málaga (IBIMA), Malaga, Spain. 3 BIONAND, Andalusian Centre for Nanomedicine & Biotechnology (Junta de Andalucía-Universidad de Málaga), Malaga, Spain. 4 Department of Molecular Biology and Biochemistry, University of Seville, Seville, Spain.…”

Section: Supplementary Informationmentioning

confidence: 99%

“…In congenital hydrocephalus, there is an active accumulation of cerebrospinal fluid with a prevalence of 4-6 individuals per 10,000 births [1,2]. Clinically, it manifests with ventriculomegaly (expansion of the cerebral ventricles) and increased intracranial pressure [3], thus adversely affecting brain tissue enclosed by the skull [4]. The main pathological consequences of congenital hydrocephalus include damage to the cerebral white matter, ischemia/hypoxia, inflammation, edema, and gliosis [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

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Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells

et al. 2020

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Background: In obstructive congenital hydrocephalus, cerebrospinal fluid accumulation is associated with high intracranial pressure and the presence of periventricular edema, ischemia/hypoxia, damage of the white matter, and glial reactions in the neocortex. The viability and short time effects of a therapy based on bone marrow-derived mesenchymal stem cells (BM-MSC) have been evaluated in such pathological conditions in the hyh mouse model. Methods: BM-MSC obtained from mice expressing fluorescent mRFP1 protein were injected into the lateral ventricle of hydrocephalic hyh mice at the moment they present a very severe form of the disease. The effect of transplantation in the neocortex was compared with hydrocephalic hyh mice injected with the vehicle and nonhydrocephalic littermates. Neural cell populations and the possibility of transdifferentiation were analyzed. The possibility of a tissue recovering was investigated using 1 H High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance (1 H HR-MAS NMR) spectroscopy, thus allowing the detection of metabolites/osmolytes related with hydrocephalus severity and outcome in the neocortex. An in vitro assay to simulate the periventricular astrocyte reaction conditions was performed using BM-MSC under high TNFα level condition. The secretome in the culture medium was analyzed in this assay.

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Section: Supplementary Informationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells

et al. 2020

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“…Hydrocephalus, the most common disease treated by pediatric neurosurgeons, is a physiological disorder of the cerebrospinal fluid (CSF) typically associated with high intraventricular pressure (ICP) and a consequent expansion of the cerebral ventricles [ 1 ]. Pediatric hydrocephalus can be acquired or congenital, and in the latter case, obstruction of the cerebral aqueduct is one of the most common causes [ 1 , 2 , 3 ]. The pathophysiology of congenital obstructive hydrocephalus comprises alterations in the normal structure, physiology, and biochemistry of the brain, including ischemia/hypoxia, damage to cerebral white matter, inflammation, and microglial/astroglial reactions [ 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Generation of Periventricular Reactive Astrocytes Overexpressing Aquaporin 4 Is Stimulated by Mesenchymal Stem Cell Therapy

García-Bonilla

Ojeda-Pérez

Shumilov

et al. 2023

IJMS

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Aquaporin-4 (AQP4) plays a crucial role in brain water circulation and is considered a therapeutic target in hydrocephalus. Congenital hydrocephalus is associated with a reaction of astrocytes in the periventricular white matter both in experimental models and human cases. A previous report showed that bone marrow-derived mesenchymal stem cells (BM-MSCs) transplanted into the lateral ventricles of hyh mice exhibiting severe congenital hydrocephalus are attracted by the periventricular astrocyte reaction, and the cerebral tissue displays recovery. The present investigation aimed to test the effect of BM-MSC treatment on astrocyte reaction formation. BM-MSCs were injected into the lateral ventricles of four-day-old hyh mice, and the periventricular reaction was detected two weeks later. A protein expression analysis of the cerebral tissue differentiated the BM-MSC-treated mice from the controls and revealed effects on neural development. In in vivo and in vitro experiments, BM-MSCs stimulated the generation of periventricular reactive astrocytes overexpressing AQP4 and its regulatory protein kinase D-interacting substrate of 220 kDa (Kidins220). In the cerebral tissue, mRNA overexpression of nerve growth factor (NGF), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 (HIF1α), and transforming growth factor beta 1 (TGFβ1) could be related to the regulation of the astrocyte reaction and AQP4 expression. In conclusion, BM-MSC treatment in hydrocephalus can stimulate a key developmental process such as the periventricular astrocyte reaction, where AQP4 overexpression could be implicated in tissue recovery.

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“…Ischemia/hypoxia and alterations in the periventricular white matter (PVWM), including myelin destruction and loss of oligodendrocytes progenitors, have been described in human and experimental models [ 8 – 11 ]. Inflammation has also been suggested to play a role in the pathogenesis of acquired hydrocephalus [ 12 ] through the increase of microglial and astroglial reactions [ 6 , 9 , 13 , 14 ]. In addition, the levels of pro-inflammatory molecules, such as interleukins IL1α, IL4, IL6, IL12, Tumor Necrosis Factor-alpha (TNF-α), or Transforming Growth Factor-beta, some of them activated by the Toll Like Receptor 4 downstream pathway [ 15 ], in the CSF correlate with the severity of the disease [ 8 , 12 , 16 – 23 ].…”

Section: Introductionmentioning

confidence: 99%

Acquired hydrocephalus is associated with neuroinflammation, progenitor loss, and cellular changes in the subventricular zone and periventricular white matter

García-Bonilla

Castañeyra-Ruiz

Zwick

et al. 2022

Fluids Barriers CNS

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Background Hydrocephalus is a neurological disease with an incidence of 80–125 per 100,000 births in the United States. Neuropathology comprises ventriculomegaly, periventricular white matter (PVWM) alterations, inflammation, and gliosis. We hypothesized that hydrocephalus in a pig model is associated with subventricular and PVWM cellular alterations and neuroinflammation that could mimic the neuropathology described in hydrocephalic infants. Methods Hydrocephalus was induced by intracisternal kaolin injections in 35-day old female pigs (n = 7 for tissue analysis, n = 10 for CSF analysis). Age-matched sham controls received saline injections (n = 6). After 19–40 days, MRI scanning was performed to measure the ventricular volume. Stem cell proliferation was studied in the Subventricular Zone (SVZ), and cell death and oligodendrocytes were examined in the PVWM. The neuroinflammatory reaction was studied by quantifying astrocytes and microglial cells in the PVWM, and inflammatory cytokines in the CSF. Results The expansion of the ventricles was especially pronounced in the body of the lateral ventricle, where ependymal disruption occurred. PVWM showed a 44% increase in cell death and a 67% reduction of oligodendrocytes. In the SVZ, the number of proliferative cells and oligodendrocyte decreased by 75% and 57% respectively. The decrease of the SVZ area correlated significantly with ventricular volume increase. Neuroinflammation occurred in the hydrocephalic pigs with a significant increase of astrocytes and microglia in the PVWM, and high levels of inflammatory interleukins IL-6 and IL-8 in the CSF. Conclusion The induction of acquired hydrocephalus produced alterations in the PVWM, reduced cell proliferation in the SVZ, and neuroinflammation.

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Congenital Hydrocephalus

Cited by 4 publications

References 190 publications

Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells

Neocortical tissue recovery in severe congenital obstructive hydrocephalus after intraventricular administration of bone marrow-derived mesenchymal stem cells

Generation of Periventricular Reactive Astrocytes Overexpressing Aquaporin 4 Is Stimulated by Mesenchymal Stem Cell Therapy

Acquired hydrocephalus is associated with neuroinflammation, progenitor loss, and cellular changes in the subventricular zone and periventricular white matter

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