2016
DOI: 10.1128/aac.02429-15
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Inhibition of Hippocampal Regeneration by Adjuvant Dexamethasone in Experimental Infant Rat Pneumococcal Meningitis

Abstract: 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 … Show more

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Cited by 9 publications
(7 citation statements)
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“…In a comprehensive meta-analysis, adjunctive anti-inflammatory corticosteroids were shown to improve the outcome of adults with PM in high-income countries and of children with meningitis caused by Haemophilus influenzae type b, without showing a clear benefit of corticosteroids in children with PM (27). Multiple experimental models of bacterial meningitis with adjunctive dexamethasone demonstrated aggravated mortality and acute hippocampal injury with subsequent learning and memory deficits, especially in infant rodents (23,30,31,83,84). As there is no substantial evidence supporting the use of dexamethasone in children with PM, we did not include it in our study focusing on pediatric PM.…”
Section: Discussionmentioning
confidence: 99%
“…In a comprehensive meta-analysis, adjunctive anti-inflammatory corticosteroids were shown to improve the outcome of adults with PM in high-income countries and of children with meningitis caused by Haemophilus influenzae type b, without showing a clear benefit of corticosteroids in children with PM (27). Multiple experimental models of bacterial meningitis with adjunctive dexamethasone demonstrated aggravated mortality and acute hippocampal injury with subsequent learning and memory deficits, especially in infant rodents (23,30,31,83,84). As there is no substantial evidence supporting the use of dexamethasone in children with PM, we did not include it in our study focusing on pediatric PM.…”
Section: Discussionmentioning
confidence: 99%
“…The beneficial effect of corticosteroids in paediatric bacterial meningitis was, however, exclusively demonstrated for meningitis caused by Haemophilus influenzae and not for PM or other causative pathogens [ 24 ]. In animal models for infant PM, the outcome after adjunctive dexamethasone therapy was aggravated with regard to survival, weight loss, hippocampal apoptosis and memory performance [ 9 , 25 , 26 ]. Since this present study was performed in a model of infant PM, we did not compare treatment regimens to adjunctive dexamethasone, which has previously been shown to impair the outcome in comparison to CRO monotherapy [ 9 , 25 28 ].…”
Section: Discussionmentioning
confidence: 99%
“…In a comprehensive meta-analysis, dexamethasone was shown to improve the outcome of adults with PM and children with meningitis caused by Haemophilus influenzae type b—without showing a beneficial effect in pediatric PM [38]. In experimental pediatric PM, dexamethasone even aggravates hippocampal regeneration and learning deficiency [32, 40]. Therefore, it is important to find alternative therapeutic approaches to alleviate the diseases burden in children suffering from PM.…”
Section: Introductionmentioning
confidence: 99%