Dendritic and Synaptic Degeneration in Pyramidal Neurons of the Sensorimotor Cortex in Neonatal Mice With Kaolin-Induced Hydrocephalus

Femi-Akinlosotu, Omowumi; Shokunbi, Temitayo; Naicker, Thajasvarie

doi:10.3389/fnana.2019.00038

Cited by 11 publications

(14 citation statements)

References 60 publications

(71 reference statements)

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“…Notwithstanding the common finding of neuroinflammation in pediatric hydrocephalus (Savman et al, 2002;Ulfig et al, 2004;Schmitz et al, 2007;Habiyaremye et al, 2017), the role of inflammation and activated myeloid cells in hydrocephalic brains remains largely unknown. The common histologic changes in neurons in neonatal hydrocephalus, including reduced dendritic arborization and axonal growth, have been considered to be secondary to ventriculomegaly and tissue compression (Del Bigio, 2010;Femi-Akinlosotu et al, 2019). Therefore, the clinical treatment for hydrocephalus has been almost solely focused on CSF diversion (Kahle et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

The Anti-Inflammatory Agent Bindarit Attenuates the Impairment of Neural Development through Suppression of Microglial Activation in a Neonatal Hydrocephalus Mouse Model

et al. 2022

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Neonatal hydrocephalus presents with various degrees of neuroinflammation and long-term neurologic deficits in surgically treated patients, provoking a need for additional medical treatment. We previously reported elevated neuroinflammation and severe periventricular white matter damage in the progressive hydrocephalus (prh) mutant which contains a point mutation in the Ccdc39 gene, causing loss of cilia-mediated unidirectional CSF flow. In this study, we identified cortical neuropil maturation defects such as impaired excitatory synapse maturation and loss of homeostatic microglia, and swimming locomotor defects in early postnatal prh mutant mice. Strikingly, systemic application of the anti-inflammatory small molecule bindarit significantly supports healthy postnatal cerebral cortical development in the prh mutant. While bindarit only mildly reduced the ventricular volume, it significantly improved the edematous appearance and myelination of the corpus callosum. Moreover, the treatment attenuated thinning in cortical Layers II-IV, excitatory synapse formation, and interneuron morphogenesis, by supporting the ramified-shaped homeostatic microglia from excessive cell death. Also, the therapeutic effect led to the alleviation of a spastic locomotor phenotype of the mutant. We found that microglia, but not peripheral monocytes, contribute to amoeboid-shaped activated myeloid cells in prh mutants' corpus callosum and the proinflammatory cytokines expression. Bindarit blocks nuclear factor (NF)-kB activation and its downstream proinflammatory cytokines, including monocyte chemoattractant protein-1, in the prh mutant. Collectively, we revealed that amelioration of neuroinflammation is crucial for white matter and neuronal maturation in neonatal hydrocephalus. Future studies of bindarit treatment combined with CSF diversion surgery may provide long-term benefits supporting neuronal development in neonatal hydrocephalus.

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Section: Discussionmentioning

confidence: 99%

The Anti-Inflammatory Agent Bindarit Attenuates the Impairment of Neural Development through Suppression of Microglial Activation in a Neonatal Hydrocephalus Mouse Model

et al. 2022

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“…This is similar to our earlier study of the sensorimotor cortex in neonatal mice, although we reported diminished arborization in the basal but not apical dendrites. 34 Being the major output of the hippocampus, morphological changes in the CA 1 pyramidal neurons provide structural data to explain deficits in learning and memory. 35 Dendrites are the branched projections of a neuron that act to propagate the electrochemical stimulation received from other neural cells to the cell body, or soma, of the neuron from which the dendrites project.…”

Section: Discussionmentioning

confidence: 99%

Pyramidal cell morphology and cell death in the hippocampus of adult mice with experimentally induced hydrocephalus

Shokunbi¹,

Olopade²,

Femi-Akinlosotu³

et al. 2020

Nig. J. Paed.

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Background: Hippocampus is a neural structure in the temporal lobe that plays a crucial role in learning and memory. Cognitive impairment with learning disabilities is a common feature in hydrocephalus and is more prominent in adult-onset hydrocephalus. The aim of this study is to describethe morphological alterations in the pyramidal cells of the hippocampus of adult hydrocephalic mice. Method: Hydrocephalus was induced in adult albino mice by intra-cisternal injection of kaolin suspension (250 mg/ml in sterile water). They were sacrificed 7, 14 and 21 days post-induction. Morphological analysis was carried out on hematoxylin and eosinstained coronal sections of the hippocampus: the pyramidal neurons (normal and pyknotic) in the CA1 and CA3 subregions were counted and the pyknotic index (PI) was calculated. The somatic and dendritic features of Golgistained pyramidal neurons were examined by light microscopy in both hydrocephalic and control mice. Result: The PI was significantly greater in the CA1 region of the hippocampus in the hydrocephalic groups compared to the agematched controls. The dendritic processes of pyramidal neurons in the CA1 region were fewer with shorter terminal branches in the hydrocephalic mice than in controls; this was pronounced at 7 days post-induction. In the CA3 region, there was no difference in dendritic arborization between hydrocephalic and control mice. Conclusion: Acute adult-onset hydrocephalus was associated with increased pyknosis and reduced dendritic arborization in hippocampal pyramidal cells in the CA1 but not CA3 region. Keywords: Hippocampal pyramidal cell, Hydrocephalus, Pyknotic index, Golgi stain

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“…We studied the neuronal population in the sensorimotor cortex and the behavioural pattern of neonatal mice following induction on the first day of birth of hydrocephalus by intracisternal injection of kaolin, a widely employed method in experimental hydrocephalus [28][29][30][31][32][33]. We examined neurobehaviour in the pups using surface righting, cliff aversion, and negative geotaxis and studied the cortical lamination and pyramidal cell populations in the sensorimotor cortex.…”

Section: Discussionmentioning

confidence: 99%

“…Control animals were sham-operated with needle insertion only. This method is similar to techniques in previously published studies [28][29][30][31][32][33]. Each pup was observed for the appearance of developmental landmarks and general health and behaviour.…”

Section: Introductionmentioning

confidence: 96%

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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Dendritic and Synaptic Degeneration in Pyramidal Neurons of the Sensorimotor Cortex in Neonatal Mice With Kaolin-Induced Hydrocephalus

Cited by 11 publications

References 60 publications

The Anti-Inflammatory Agent Bindarit Attenuates the Impairment of Neural Development through Suppression of Microglial Activation in a Neonatal Hydrocephalus Mouse Model

The Anti-Inflammatory Agent Bindarit Attenuates the Impairment of Neural Development through Suppression of Microglial Activation in a Neonatal Hydrocephalus Mouse Model

Pyramidal cell morphology and cell death in the hippocampus of adult mice with experimentally induced hydrocephalus

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

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