The effects of repeated corticosteroid administration on the neurogenesis in the neonatal rat

Kanagawa, Takeshi; Tomimatsu, Takuji; Hayashi, Satoru; Shioji, Mitsunori; Fukuda, Hiromitsu; Shimoya, Koichiro; Murata, Yuji

doi:10.1016/j.ajog.2005.06.015

Cited by 38 publications

(22 citation statements)

References 31 publications

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“…Neural precursor cells and immature neurons in the hippocampus were shown to be sensitive to the proapoptotic actions of DXM in neonatal rats, leading to significant and sustained reductions in the volume of the dentate gyrus (18). In addition, a one to three day DXM regimen in 4-to 7-day-old rats significantly decreased brain weight, which was associated with a decrease in BrdU-labeled cells in the subpial granular layer (SGL), the subventricular zone (SVZ), and the cortex (16). The same decline in BrdU incorporation following DXM application was also shown in in vitro investigations on embryonic rat neural stem cells (17).…”

Section: Discussionmentioning

confidence: 99%

“…In addition to an aggravated hippocampal apoptosis, transcriptome analysis suggests that DXM-induced hippocampal damage in PM may be related to a decrease of proneurogenic processes in the infant rat model (12). Of note, the proapoptotic and antiproliferative properties of DXM on embryonic and neonatal rat hippocampal cells have been previously reported outside of the context of PM (16)(17)(18). The hippocampus is a site of persistent neurogenesis (19), and an increase in the cellular proliferative capacity that might be involved in the regeneration of PM-induced brain damage has been observed in the hippocampi of infant rats (20), adult mice (21), and even patients who died from meningitis (22).…”

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confidence: 99%

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Inhibition of Hippocampal Regeneration by Adjuvant Dexamethasone in Experimental Infant Rat Pneumococcal Meningitis

Bally

Grandgirard

Leib

2016

Antimicrob Agents Chemother

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Pneumococcal meningitis (PM) causes neurological sequelae in up to half of surviving patients. Neuronal damage associated with poor outcome is largely mediated by the inflammatory host response. Dexamethasone (DXM) is used as an adjuvant therapy in adult PM, but its efficacy in the treatment of pneumococcal meningitis in children is controversially discussed. While DXM has previously been shown to enhance hippocampal apoptosis in experimental PM, its impact on hippocampal cell proliferation is not known. This study investigated the impact of DXM on hippocampal proliferation in infant rat PM. Eleven-day-old nursing Wistar rats (n ‫؍‬ 90) were intracisternally infected with Streptococcus pneumoniae to induce experimental meningitis. Treatment with DXM or vehicle was started 18 h after infection, concomitantly with antibiotics (ceftriaxone 100 mg/kg of body weight twice a day [b.i.d.]). Clinical parameters were monitored, and the amount of cells with proliferating activity was assessed using in vivo incorporation of bromodeoxyuridine (BrdU) and an in vitro neurosphere culture system at 3 and 4 d postinfection. DXM significantly worsened weight loss and survival. Density of BrdU-positive cells, as an index of cells with proliferating activity, was significantly lower in DXM-treated animals compared to vehicle controls (P < 0.0001). In parallel, DXM reduced neurosphere formation as an index for stem/progenitor cell density compared to vehicle treatment (P ‫؍‬ 0.01). Our findings provide clear evidence that DXM exerts an antiproliferative effect on the hippocampus in infant rat PM. We conclude that an impairment of regenerative hippocampal capacity should be taken into account when considering adjuvant DXM in the therapeutic regimen for PM in children.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Inhibition of Hippocampal Regeneration by Adjuvant Dexamethasone in Experimental Infant Rat Pneumococcal Meningitis

Bally

Grandgirard

Leib

2016

Antimicrob Agents Chemother

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“…This is characterized by attenuated secretions of corticotrophin and glucocorticoids from the pituitary and adrenal/interrenals. Unfavorable effects of glucocorticoids on growth (Mashaly, 1991;Morici et al, 1997;Glennemeier and Denver, 2002;Spencer et al, 2003;Hayward and Wingfield, 2004;Meylan and Clobert, 2005;Saino et al, 2005;Wan et al, 2005;Janczak et al, 2006;Wada and Breuner, 2008), immune function (Morici et al, 1997;Rubolini et al, 2005), neurogenesis (McEwen, 1987;Kanagawa et al, 2006;Heine and Rowitch, 2009), and survival (Mashaly, 1991;Saino et al, 2005;Janczak et al, 2006) led researchers to believe that the SHRP is an adaptive characteristic, serving to minimize detrimental effects of glucocorticoids during development.…”

Section: Introductionmentioning

confidence: 97%

Developmental changes in neural corticosteroid receptor binding capacity in altricial nestlings

Wada¹,

Breuner²

2010

Developmental Neurobiology

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Altricial nestlings typically do not show an adrenocortical response during the early post-hatch period. This may be a result of an immature hypothalamic-pituitary-adrenal axis, or an enhanced control of the axis by negative feedback. To examine whether the dampened adrenocortical response is due to higher receptor densities in hypothalamus and hippocampus, the major sites for negative feedback and tonic inhibition, we explored the ontogenetic changes in glucocorticoid (GR) and mineralocorticoid receptor (MR) binding capacities in the brain of white-crowned sparrow nestlings. During the 10-day nestling period, MR binding capacity decreased with age, whereas GR capacity was not affected. In addition, this overall decline in MR levels was driven entirely by a decline in cerebellar MR. No age-related changes were observed in hippocampal or hypothalamic areas. Our findings suggest that enhanced negative feedback does not play a major role in the attenuated adrenocortical responses seen in white-crowned sparrow nestlings.

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“…Animals in the corresponding vehicle groups received equivalent volumes of saline. These doses and modes of administration were chosen from previous studies (3,9,26). The typical total dose of HC of 5-20 mg/kg equates to ~0.2-0.6 mg/kg of Dex (17).…”

Section: Drug Treatmentmentioning

confidence: 99%

Dexamethasone but not the equivalent doses of hydrocortisone induces neurotoxicity in neonatal rat brain

et al. 2015

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Background:The use of dexamethasone (Dex) in premature infants to treat or prevent chronic lung disease adversely affects neurodevelopment. Recent clinical studies suggest that hydrocortisone (HC) is a safer alternative to Dex. We compared the effects of Dex and HC on neurotoxicity in newborn rats. Methods: Rat pups of a neurodevelopmental stage equivalent to premature human neonates were administered Dex or HC either as a single dose on postnatal day (PD) 6, repeated doses on PD 4 to 6 or tapering doses at PD 3 to 6 by i.p. injection. Brain weight, caspase-3 activity, and apoptotic cells were measured at PD 7; learning capability, memory, and motor function were measured at juvenile age. results: Dex decreased both body and brain weight gain, while HC did not. Tapering and repeated doses of Dex increased caspase-3 activity, cleaved caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells but HC, except at high doses, did not. Dex impaired learning and memory capability at juvenile age, while the rats exposed to HC showed normal cognitive behavior. conclusion: HC is probably safer to use than Dex in the immediate postnatal period in neonatal rats. Cautious extrapolation of these findings to human premature infants is required.

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The effects of repeated corticosteroid administration on the neurogenesis in the neonatal rat

Cited by 38 publications

References 31 publications

Inhibition of Hippocampal Regeneration by Adjuvant Dexamethasone in Experimental Infant Rat Pneumococcal Meningitis

Inhibition of Hippocampal Regeneration by Adjuvant Dexamethasone in Experimental Infant Rat Pneumococcal Meningitis

Developmental changes in neural corticosteroid receptor binding capacity in altricial nestlings

Dexamethasone but not the equivalent doses of hydrocortisone induces neurotoxicity in neonatal rat brain

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