A Novel Experimental Animal Model of Adult Chronic Hydrocephalus

Jusué-Torres, Ignacio; Jeon, Lee; Sankey, Eric W.; Lu, Jennifer; Vivas-Buitrago, Tito; Crawford, Joshua; Pletnikov, Mikhail V.; Xu, Jiadi; Blitz, Ari M.; Herzka, Daniel A.; Crain, Barbara J.; Hulbert, Alicia; Guerrero-Cázares, Hugo; González-Pérez, Óscar; McAllister, James P.; Quiñones‐Hinojosa, Alfredo; Rigamonti, Daniele

doi:10.1227/neu.0000000000001405

Cited by 20 publications

(14 citation statements)

References 37 publications

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“…Furthermore, differences in neurobehavioural data of kaolin-induced hydrocephalus may be due to differences in timing of injection, procedures, and severity of the hydrocephalic state [43]. In attestation to our data on the decreased movements of the hydrocephalic mice, Jusué-Torres and co-researchers also observed that increase in ventricular size in hydrocephalic rats led to locomotor impairment, resembling the course seen in adult humans with chronic hydrocephalus [44]. Developmental neurobehavioural testing is also essential for postnatal evaluation for studying behavioural teratology.…”

Section: Discussionsupporting

confidence: 76%

Changes in Neuronal Density of the Sensorimotor Cortex and Neurodevelopmental Behaviour in Neonatal Mice with Kaolin-Induced Hydrocephalus

Femi-Akinlosotu

Shokunbi

2020

Pediatr Neurosurg

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Introduction: Hydrocephalus is a disorder in which the circulation of cerebrospinal fluid is altered in a manner that leads to its accumulation in the ventricles and subarachnoid space. Its impact on the neuronal density and networks in the overlying cerebral cortex in a time-dependent neonatal hydrocephalic process is largely unknown. We hypothesize that hydrocephalus will affect the cytoarchitecture of the cerebral cortical mantle of neonatal hydrocephalic mice, which will in turn modify sensorimotor processing and neurobehaviour. Objective: The purpose of this study is to probe the effect of hydrocephalus on 3 developmental milestones (surface righting reflex, cliff avoidance reflex, and negative geotaxis) and on cortical neuronal densities in neonatal hydrocephalic mice. Methods: Hydrocephalus was induced in 1-day-old mice by intracisternal injection of sterile kaolin suspension. The pups were tested for reflex development and sensorimotor ability using surface righting reflex (PND 5, 7, and 9), cliff avoidance (PND 6), and negative geotaxis (PND 10 and 12) prior to their sacrifice on PND 7, 14, and 21. Neuronal density and cortical thickness in the sensorimotor cortex were evaluated using atlas-based segmentation of the neocortex and boundary definition in 4-μm paraffin-embedded histological sections with hematoxylin and eosin as well as cresyl violet stains. Results: Surface righting and cliff avoidance activities were significantly impaired in hydrocephalic pups but no statistically significant difference was observed in negative geotaxis in both experimental and control pups. The neuronal density of the sensorimotor cortex was significantly higher in hydrocephalic mice than in age-matched controls on PND 14 and 21 (373.20 ± 21.54 × 10−6 μm2 vs. 157.70 ± 21.88 × 10−6 μm2; 230.0 ± 44.1 × 10−6 μm2 vs. 129.60 ± 3.72 × 10−6 μm2, respectively; p < 0.05). This was accompanied by reduction in the cortical thickness (µm) in the hydrocephalic mice on PND 7 (2,409 ± 43.37 vs. 3,752 ± 65.74, p < 0.05), PND 14 (2,035 ± 322.10 vs. 4,273 ± 67.26, p < 0.05), and PND 21 (1,676 ± 33.90 vs. 4,945 ± 81.79, p < 0.05) compared to controls. Conclusion: In this murine model of neonatal hydrocephalus, the quantitative changes in the cortical neuronal population may play a role in the observed changes in neurobehavioural findings.

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Section: Discussionsupporting

confidence: 76%

Changes in Neuronal Density of the Sensorimotor Cortex and Neurodevelopmental Behaviour in Neonatal Mice with Kaolin-Induced Hydrocephalus

Femi-Akinlosotu

Shokunbi

2020

Pediatr Neurosurg

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“…Some clinical studies have reported that significantly increased inflammatory fibrogenic cytokines or ferritin levels in CSF are associated with sNPH after subarachnoid haemorrhage515253. Additionally, a rat model of communicating hydrocephalus by injecting kaolin in the subarachnoid spaces mimics human sNPH545556. In a kaolin-induced sNPH model, the subarachnoid spaces were obstructed with the number of macrophages and severe fibrosis5556.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, a rat model of communicating hydrocephalus by injecting kaolin in the subarachnoid spaces mimics human sNPH545556. In a kaolin-induced sNPH model, the subarachnoid spaces were obstructed with the number of macrophages and severe fibrosis5556. Inflammation in CSF is known to be associated with arachnoid and pia matter fibrosis57, which might lead to the closure of subarachnoid spaces.…”

Section: Discussionmentioning

confidence: 99%

Choroidal fissure acts as an overflow device in cerebrospinal fluid drainage: morphological comparison between idiopathic and secondary normal-pressure hydrocephalus

Yamada

Ishikawa

Iwamuro

et al. 2016

Sci Rep

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To clarify the pathogenesis of two different types of adult-onset normal-pressure hydrocephalus (NPH), we investigated cerebrospinal fluid distribution on the high-field three-dimensional MRI. The subarachnoid spaces in secondary NPH were smaller than those in the controls, whereas those in idiopathic NPH were of similar size to the controls. In idiopathic NPH, however, the basal cistern and Sylvian fissure were enlarged in concurrence with ventricular enlargement towards the z-direction, but the convexity subarachnoid space was severely diminished. In this article, we provide evidence that the key cause of the disproportionate cerebrospinal fluid distribution in idiopathic NPH is the compensatory direct CSF communication between the inferior horn of the lateral ventricles and the ambient cistern at the choroidal fissure. In contrast, all parts of the subarachnoid spaces were equally and severely decreased in secondary NPH. Blockage of CSF drainage from the subarachnoid spaces could cause the omnidirectional ventricular enlargement in secondary NPH.

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“…To unveil the pathogenesis of brain damage in hydrocephalus and develop more effective nonsurgical treatments, researchers have developed different animal models such as intraventricular injection of blood or kaolin to induce hydrocephalus in rats. 14 , 15 At the same time, some congenital hydrocephalus models characterized by aqueduct stenosis, ependymal stripping, and astrocytes activation have also been applied. 16 , 17 Although animal models cannot fully simulate human body condition, they still play important roles in hydrocephalus research.…”

Section: Introductionmentioning

confidence: 99%

Novel therapeutics for hydrocephalus: Insights from animal models

Wang

Tan

et al. 2021

CNS Neurosci Ther

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Hydrocephalus is a cerebrospinal fluid physiological disorder that causes ventricular dilation with normal or high intracranial pressure. The current regular treatment for hydrocephalus is cerebrospinal fluid shunting, which is frequently related to failure and complications. Meanwhile, considering that the current nonsurgical treatments of hydrocephalus can only relieve the symptoms but cannot eliminate this complication caused by primary brain injuries, the exploration of more effective therapies has become the focus for many researchers. In this article, the current research status and progress of nonsurgical treatment in animal models of hydrocephalus are reviewed to provide new orientations for animal research and clinical practice.

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A Novel Experimental Animal Model of Adult Chronic Hydrocephalus

Abstract: NPH, normal pressure hydrocephalus.

Cited by 20 publications

References 37 publications

Changes in Neuronal Density of the Sensorimotor Cortex and Neurodevelopmental Behaviour in Neonatal Mice with Kaolin-Induced Hydrocephalus

Changes in Neuronal Density of the Sensorimotor Cortex and Neurodevelopmental Behaviour in Neonatal Mice with Kaolin-Induced Hydrocephalus

Choroidal fissure acts as an overflow device in cerebrospinal fluid drainage: morphological comparison between idiopathic and secondary normal-pressure hydrocephalus

Novel therapeutics for hydrocephalus: Insights from animal models

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