Hydrocephalus: the role of cerebral aquaporin-4 channels and computational modeling considerations of cerebrospinal fluid

Desai, Bhargav; Hsu, Ying; Schneller, Benjamin; Hobbs, Jonathan G.; Mehta, Ankit I.; Linninger, Andreas A.

doi:10.3171/2016.7.focus16191

Cited by 46 publications

(38 citation statements)

References 137 publications

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“…However, another group of studies has shown that the role of cerebrospinal fluid (CSF) hydrodynamics is highly prominent in managing many diseases associated with the CSF circulation system 21,[33][34][35][36][37][38] . Hydrodynamic studies of CSF have shown that the incidence of CM-I is accompanied by changes in hydrodynamic parameters of CSF flow 21,[39][40][41][42][43][44][45][46] .…”

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confidence: 99%

Correlation of a new hydrodynamic index with other effective indexes in Chiari I malformation patients with different associations

Gholampour

2020

Sci Rep

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This study aimed to find a new CSF hydrodynamic index to assess Chiari type I malformation (CM-I) patients’ conditions and examine the relationship of this new index with morphometric and volumetric changes in these patients and their clinical symptoms. To this end, 58 CM-I patients in four groups and 20 healthy subjects underwent PC-MRI. Ten morphometric and three volumetric parameters were calculated. The CSF hydrodynamic parameters were also analyzed through computational fluid dynamic (CFD) simulation. The maximum CSF pressure was identified as a new hydrodynamic parameter to assess the CM-I patients’ conditions. This parameter was similar in patients with the same symptoms regardless of the group to which they belonged. The result showed a weak correlation between the maximum CSF pressure and the morphometric parameters in the patients. Among the volumetric parameters, PCF volume had the highest correlation with the maximum CSF pressure, which its value being higher in patients with CM-I/SM/scoliosis (R2 = 65.6%, P = 0.0022) than in the other patients. PCF volume was the more relevant volumetric parameter to assess the patients’ symptoms. The values of PCF volume were greater in patients that headache symptom was more obvious than other symptoms, as compared to the other patients.

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confidence: 99%

Correlation of a new hydrodynamic index with other effective indexes in Chiari I malformation patients with different associations

Gholampour

2020

Sci Rep

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“…Moreover, in congenital hydrocephalus patients, the cerebrospinal fluid also shows a higher AQP4 expression [ 13 ]. A variety of studies show that the AQP4 level in cerebrospinal fluid and parenchyma of subjects with hydrocephalus is elevated, and this disturbance is correlated with hydrocephalus severity [ 13 , 14 , 16 ]. This suggests that AQP4 has a relationship with hydrocephalus.…”

Section: Discussionmentioning

confidence: 99%

Aquaporin 4 Silencing Aggravates Hydrocephalus Induced by Injection of Autologous Blood in Rats

Guo

Zhan

et al. 2018

Med Sci Monit

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BackgroundAquaporin 4 (AQP4), the most abundant aquaporin in the brain, is a type of bidirectional water channel controlling the brain-water balance and plays a critical role in physiologic and pathologic water balance in the brain. AQP4 was reported to be elevated in hydrocephalus; therefore, we hypothesized that AQP4 contributes to hydrocephalus. In this study, the role of AQP4 in hydrocephalus was explored.Material/MethodsThe hydrocephalus rat model was established by injection of autologous blood. On Day 1 and Day 3 after injection of autologous blood, magnetic resonance imaging (MRI) and hematoxylin-eosin (HE) staining were performed to detect the changes in ventricles, and quantitative real-time PCR (qRT-PCR) and immunohistochemistry were carried out to detect the changes in AQP4 level. Thereafter, an AQP4-specific siRNA was used to downregulate AQP4. Then, on Day 3 after injection of autologous blood, the levels of AQP4 and connexin-43 were detected by qRT-PCR, immunohistochemistry, immunofluorescence, or Western blot analysis. MRI and HE staining were performed to detect the changes in ventricles, and Evans blue extravasation assay was used to assess blood-brain barrier integrity.ResultsThe hydrocephalus rat model was established successfully, and hydrocephalus rats showed a higher AQP4 level. Silencing AQP4 aggravated the hydrocephalus, with enlarged lateral ventricles and destruction of ependymal integrity and blood-brain barrier.ConclusionsOur study demonstrates that silencing AQP4 aggravates hydrocephalus, indicating that AQP4 protects against hydrocephalus.

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“…Further data suggest that aquaporin-4 channels can be implicated in the pathophysiology of iNPH [31]. Aquaporin-4 channels are transmembrane proteins that facilitate water transport in the brain and play roles in fluid secretion, cell migration, brain edema, metabolism, and many aspects of cell homeostasis; a modulation of their activity could be a potential target for pharmacological management of iNPH.…”

Section: Imaging Studiesmentioning

confidence: 99%

“…In patients who are poor candidates for shunt surgery, repeated lumbar punctures in combination with acetazolamide may be considered [45]. Recent studies on aquaporin-4 channels suggest interesting perspectives for future pharmacological treatment of iNPH [31].…”

Section: Managementmentioning

confidence: 99%

Clinical and Cognitive Features of Idiopathic Normal Pressure Hydrocephalus

Sinforiani¹,

Pacchetti²,

Picascia³

et al. 2018

Hydrocephalus - Water on the Brain

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Introduction: Idiopathic normal pressure hydrocephalus (iNPH) is characterized by dilated cerebral ventricles with progressive impaired gait, cognition, and urinary control. Firstly described in 1965 by Hakim and Adam, it remains largely under-diagnosed. The diagnosis is based on clinical and imaging (CT or MRI) investigations; a timely diagnosis and cerebrospinal fluid (CSF) shunt surgery has reported to be beneficial in 60 up to 80% of the cases. Body: The severity of motor and cognitive disturbances varies widely and it can be difficult to distinguish iNPH from other neurodegenerative disorders. The cognitive and behavioral disturbances have been commonly described as "fronto-subcortical dysfunction". However, this definition is reductive not encompassing the entire cognitive spectrum of iNPH deficits. In our sample we found an impairment in respect to healthy controls in all the neuropsychological tests, but verbal memory. We could also find a positive correlation between the severity of cognition deficit and disease progression, suggesting a common pathological mechanism. Conclusions: iNPH can be reliably diagnosed with an organized approach. Neurologists play an essential role in the care of patients and a multidisciplinary team can improve this process. An early shunt surgery might contain the progression of the disturbances and also possibly prevent their development.

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Hydrocephalus: the role of cerebral aquaporin-4 channels and computational modeling considerations of cerebrospinal fluid

Cited by 46 publications

References 137 publications

Correlation of a new hydrodynamic index with other effective indexes in Chiari I malformation patients with different associations

Correlation of a new hydrodynamic index with other effective indexes in Chiari I malformation patients with different associations

Aquaporin 4 Silencing Aggravates Hydrocephalus Induced by Injection of Autologous Blood in Rats

Clinical and Cognitive Features of Idiopathic Normal Pressure Hydrocephalus

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