Effect of Pneumolysin on Rat Brain Ciliary Function: Comparison of Brain Slices with Cultured Ependymal Cells

Hirst, Robert A.; Rutman, Andrew; Sikand, Kulvinder; Andrew, Peter W.; Mitchell, Timothy J.; O’Callaghan, Christopher

doi:10.1203/00006450-200003000-00016

Cited by 35 publications

(48 citation statements)

References 11 publications

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“…That study reported a significant reduction in CBF almost immediately after exposure to RSV, with complete ciliostasis as early as 6 h post-infection [9]. In our experience the rapid onset of ciliostasis is frequently attributed to the presence of a toxin or to the nonphysiological nature of the carrier fluid; solutions with a low pH can cause rapid ciliostasis [18]. Another study reported that the addition of unwashed ultraviolet-irradiated RSV increased toxicity to HeLa cells, suggesting their viral preparation may have contained a toxic contaminant [13].…”

Section: Basal Cell Cultures Infected With Rsv Increase Secretion Of mentioning

confidence: 97%

Ciliary dyskinesia is an early feature of respiratory syncytial virus infection

Smith

Kulkarni

Radhakrishnan

et al. 2013

European Respiratory Journal

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Respiratory syncytial virus is a major cause of respiratory disease. There are conflicting accounts of the response of human epithelial cells to respiratory syncytial virus and a lack of data on its effect on ciliary function. Our aim was to study the early stages of respiratory syncytial virus infection of primary human basal and ciliated cultures.Using high speed videomicroscopy, we found that ciliary beat frequency was unaffected by respiratory syncytial virus infection over 72 h; however, ciliary dyskinesia significantly increased within 24 h of infection (p,0.05). Transmission electron microscopy revealed that ultrastructural abnormalities were confined to ciliated cells, including increased cilia loss and mitochondrial damage. Confocal immunofluorescence microscopy showed that respiratory syncytial virus antigen gradually spread from the cell surface to the ciliary tip of infected cells over 3 days. Interestingly, ciliated cultures secreted fewer viruses than basal (progenitor) cell cultures and produced a chemokine response focused on recruitment of neutrophils.This study highlights differences in infection models and underscores the need to explore further the role of ciliated cells in the establishment of respiratory syncytial virus infection.Increased ciliary dyskinesia combined with ciliary loss and epithelial damage is likely to result in reduced mucociliary clearance early in the infective process. @ERSpublications Increased ciliary dyskinesia with ciliary loss and epithelial damage can result in reduced mucociliary clearance

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Section: Basal Cell Cultures Infected With Rsv Increase Secretion Of mentioning

confidence: 97%

Ciliary dyskinesia is an early feature of respiratory syncytial virus infection

Smith

Kulkarni

Radhakrishnan

et al. 2013

European Respiratory Journal

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“…Ciliated rat ependymal cells were grown using a method adapted from Wiebel and colleagues (Weibel et al, 1986) and described previously (Hirst et al, 2000).…”

Section: Ependymal Cell Culturementioning

confidence: 99%

“…Ependymal cilia also have been shown to play an important role in host defence against pathogens (Hirst et al, 2003;Hirst et al, 2000;Mohammed et al, 1999). In addition, a recent study (Sawamoto et al, 2006) has shown that ependymal cilia are responsible for the formation of gradients of CSF guidance molecules that direct neuroblast movement in the brain parenchyma.…”

Section: Introductionmentioning

confidence: 99%

“…We have previously described a primary rat ependymal culture model that allows ciliary function to be studied over time (Hirst et al, 2000). An often ignored fact regarding the ciliary function is that following certain topical toxic insults the CBF remains unchanged whilst the ciliary amplitude, and hence function, may be disturbed (Chilvers and O'Callaghan, 2000).…”

Section: Introductionmentioning

confidence: 99%

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PACAP27 regulates ciliary function in primary cultures of rat brain ependymal cells

et al. 2008

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Ependymal cells line the brain ventricles and separate the CSF from the underlying neuronal tissue. The function of ependymal cilia is largely unclear however they are reported to be involved in the regulation of CSF homeostasis and host defence against pathogens. Here we present data that implicates a role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the inhibition of ependymal ciliary function, and also that the PACAP effects are not entirely dependent on adenylyl cyclase activation. Primary ependymal cultures were treated with increasing doses of PACAP27 or adenylyl cyclase toxin (ACT), and ciliary beating was recorded using high-speed digital video imaging. Ciliary beat frequency (CBF) and amplitude were determined from the videos. Ependymal CBF and ciliary amplitude were attenuated by PACAP27 in a concentration-and time-dependent manner. The peptide antagonist PACAP6-27 blocked PACAP27-induced decreases in amplitude and CBF.Treatment with ACT caused a decrease in amplitude but had no effect on CBF, this suggests that the inhibition of CBF and amplitude seen with PACAP27 may not be completely explained by G s -AC-cAMP pathway. We present here the first observational study to show that activation of PAC1 receptors with PACAP27 has an important role to play in the regulation of ependymal ciliary function.

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“…Because the vascular epithelial cells regulate the passage of molecules from blood to CSF and the ciliated ependyma has a similar function in the regulation of molecules from CSF to brain, it is reasonable to hypothesize that the effect of pneumolysin on each cell type will share common characteristics. Hirst et al have shown that pneumolysin is toxic to ciliated ependymal cells [2,3].…”

Section: Introductionmentioning

confidence: 99%

Meningitis Induced by Streptococcus Pneumoniae Elicits Cellular Damage but not DNA Damage during the Acute Phase of Infection in the Hippocampus of Wistar Rats

Santhosh¹,

Bairy²

2014

AJHR

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Abstract:Pneumococcal meningitis is associated with high mortality and morbidity. Great majority of survivors are affected by neurological sequelae due to a wide spectrum of brain injury mainly affecting the cortex and hippocampus. Published data suggest histomorphological observations of these sequelae indicating a pattern of brain damage characterized by necrotic tissue damage in the cerebral cortex and apoptosis of neurons in the hippocampal dentate gyrus. Aim of the present study was to investigate and correlate data for any DNA damage due to the effect of pneumococcal meningitis on the hippocampus in Wistar rats, during the acute phase of the infection. Thirty days old rats were divided into normal control (NC) and meningitis (M) groups. Rats in the meningitis group were infected with Streptococcus pneumoniae, intracisternally on postnatal day 31. The concentration of the bacterial suspension in phosphate-buffered saline (PBS) was 1×10 6 CFU/ml. The rats were kept under observation for 18 hrs for clinical symptoms of meningitis to develop. 10-50µl of the CSF sample was collected for confirmation by gram's staining and culture. The rats were perfused transcardially with saline followed by 10% formalin. Brains were removed, processed for paraffin sectioning and stained with cresyl violet staining. Neurodegeneration in the hippocampal CA1, CA3 and dentate hilus were quantified. DNA damage was assessed by the alkaline single-cell gel electrophoresis "comet assay" method. The hippocampal sub-regions showed neurodegeneration in the form of cellular damage. Significant fractions of neurons in the above regions were darkly stained and were irregular in shape. There was 56-81% neuronal loss in these regions. The surviving neurons showed 34-45% decrease in cell diameter and 28-29% decrease in the cross-sectional area in the hippocampal sub regions. But there were no DNA damage observed in all the regions of the hippocampus as a whole. Pneumococcal meningitis that was induced in the 30 days old rats conformed to the clinical parameters observed for meningitis and the histological analysis showed cellular damage likewise; but most interestingly there was no DNA damage in the hippocampus. This could be due to the fact that the rats were only in the acute phase of infection. Most probably, the time required for the DNA damage to occur would require that the rats proceed to a chronic phase. This finding could very well hold hope for meningitis cases that could be salvaged during the acute phase itself, thereby curtailing the neurological sequelae commonly observed after recovering from an untreated or chronic pneumococcal infection.

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Effect of Pneumolysin on Rat Brain Ciliary Function: Comparison of Brain Slices with Cultured Ependymal Cells

Cited by 35 publications

References 11 publications

Ciliary dyskinesia is an early feature of respiratory syncytial virus infection

Ciliary dyskinesia is an early feature of respiratory syncytial virus infection

PACAP27 regulates ciliary function in primary cultures of rat brain ependymal cells

Meningitis Induced by Streptococcus Pneumoniae Elicits Cellular Damage but not DNA Damage during the Acute Phase of Infection in the Hippocampus of Wistar Rats

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