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Erythropoietin protects newborn rat against sevoflurane-induced neurotoxicity.
Paediatr Anaesth. 2014 Jul; 24(7):749-59.PA

Abstract

INTRODUCTION

Recent data on newborn animals exposed to anesthetics have raised safety concerns regarding anesthesia practices in young children. Indeed, studies on rodents have demonstrated a widespread increase in brain apoptosis shortly after exposure to sevoflurane, followed by long-term neurologic impairment. In this context, we aimed to evaluate the protective effect of rh-EPO, a potent neuroprotective agent, in rat pups exposed to sevoflurane.

MATERIAL AND METHODS

At postnatal day 7, 75 rat pups were allocated into three groups: SEVO + EPO (n = 27) exposed to sevoflurane 2 vol% (0.5 MAC) for 6 h in an air/O2 mixture (60/40) + 5000 UI.kg(-1) rh-EPO IP; SEVO (n = 27) exposed to sevoflurane + vehicle IP; and CONTROL (n = 21) exposed to the mixture without sevoflurane + vehicle IP. Three days after anesthesia (D10), apoptosis was quantified on brain extract with TUNEL method and caspase 3. NGF and BDNF expression was determined by Western blotting. Rats reaching adulthood were evaluated in terms of exploration capacities (object exploration duration) together with spatial and object learning (water maze and novel object test).

RESULTS

Sevoflurane exposure impaired normal behavior in adult rats by reducing the exploratory capacities during the novel object test and impaired both spatial and object learning capacities in adult rats (water maze, ratio time to find platform 3rd trial/1st trial: 1.1 ± 0.2 vs 0.4 ± 0.1; n = 9, SEVO vs CONTROL; P = 0.01). Rh-EPO reduced sevoflurane-induced behavior and learning abnormalities in adult rats (water maze, ratio time to find platform 3rd trial/1st trial: 0.3 ± 0.1 vs 1.1 ± 0.2; n = 9, SEVO + EPO vs SEVO; P = 0.01). Three days after anesthesia, rh-EPO prevented sevoflurane-induced brain apoptosis (5 ± 3 vs 35 ± 6 apoptotic cells·mm(-2) ; n = 6, SEVO + EPO vs SEVO; P = 0.01) and elevation of caspase three level and significantly increased the brain expression of BDNF and NGF (n = 6, SEVO + EPO vs SEVO; P = 0.01).

CONCLUSION

Six hours of sevoflurane anesthesia in newborn rats induces significant long-term cognitive impairment. A single administration of rh-EPO immediately after postnatal exposure to sevoflurane reduces both early activation of apoptotic phenomenon and late onset of neurologic disorders.

Authors+Show Affiliations

Department of Anesthesia, APHM, CHU Timone, Marseille, France; INSERM UMR_S 1076, Aix-Marseille University, Marseille, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24725211

Citation

Pellegrini, Lionel, et al. "Erythropoietin Protects Newborn Rat Against Sevoflurane-induced Neurotoxicity." Paediatric Anaesthesia, vol. 24, no. 7, 2014, pp. 749-59.
Pellegrini L, Bennis Y, Velly L, et al. Erythropoietin protects newborn rat against sevoflurane-induced neurotoxicity. Paediatr Anaesth. 2014;24(7):749-59.
Pellegrini, L., Bennis, Y., Velly, L., Grandvuillemin, I., Pisano, P., Bruder, N., & Guillet, B. (2014). Erythropoietin protects newborn rat against sevoflurane-induced neurotoxicity. Paediatric Anaesthesia, 24(7), 749-59. https://doi.org/10.1111/pan.12372
Pellegrini L, et al. Erythropoietin Protects Newborn Rat Against Sevoflurane-induced Neurotoxicity. Paediatr Anaesth. 2014;24(7):749-59. PubMed PMID: 24725211.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Erythropoietin protects newborn rat against sevoflurane-induced neurotoxicity. AU - Pellegrini,Lionel, AU - Bennis,Youssef, AU - Velly,Lionel, AU - Grandvuillemin,Isabelle, AU - Pisano,Pascale, AU - Bruder,Nicolas, AU - Guillet,Benjamin, Y1 - 2014/04/12/ PY - 2014/01/22/accepted PY - 2014/4/15/entrez PY - 2014/4/15/pubmed PY - 2015/2/3/medline KW - erythropoietin KW - neuroprotection KW - neurotoxicity KW - newborn KW - sevoflurane SP - 749 EP - 59 JF - Paediatric anaesthesia JO - Paediatr Anaesth VL - 24 IS - 7 N2 - INTRODUCTION: Recent data on newborn animals exposed to anesthetics have raised safety concerns regarding anesthesia practices in young children. Indeed, studies on rodents have demonstrated a widespread increase in brain apoptosis shortly after exposure to sevoflurane, followed by long-term neurologic impairment. In this context, we aimed to evaluate the protective effect of rh-EPO, a potent neuroprotective agent, in rat pups exposed to sevoflurane. MATERIAL AND METHODS: At postnatal day 7, 75 rat pups were allocated into three groups: SEVO + EPO (n = 27) exposed to sevoflurane 2 vol% (0.5 MAC) for 6 h in an air/O2 mixture (60/40) + 5000 UI.kg(-1) rh-EPO IP; SEVO (n = 27) exposed to sevoflurane + vehicle IP; and CONTROL (n = 21) exposed to the mixture without sevoflurane + vehicle IP. Three days after anesthesia (D10), apoptosis was quantified on brain extract with TUNEL method and caspase 3. NGF and BDNF expression was determined by Western blotting. Rats reaching adulthood were evaluated in terms of exploration capacities (object exploration duration) together with spatial and object learning (water maze and novel object test). RESULTS: Sevoflurane exposure impaired normal behavior in adult rats by reducing the exploratory capacities during the novel object test and impaired both spatial and object learning capacities in adult rats (water maze, ratio time to find platform 3rd trial/1st trial: 1.1 ± 0.2 vs 0.4 ± 0.1; n = 9, SEVO vs CONTROL; P = 0.01). Rh-EPO reduced sevoflurane-induced behavior and learning abnormalities in adult rats (water maze, ratio time to find platform 3rd trial/1st trial: 0.3 ± 0.1 vs 1.1 ± 0.2; n = 9, SEVO + EPO vs SEVO; P = 0.01). Three days after anesthesia, rh-EPO prevented sevoflurane-induced brain apoptosis (5 ± 3 vs 35 ± 6 apoptotic cells·mm(-2) ; n = 6, SEVO + EPO vs SEVO; P = 0.01) and elevation of caspase three level and significantly increased the brain expression of BDNF and NGF (n = 6, SEVO + EPO vs SEVO; P = 0.01). CONCLUSION: Six hours of sevoflurane anesthesia in newborn rats induces significant long-term cognitive impairment. A single administration of rh-EPO immediately after postnatal exposure to sevoflurane reduces both early activation of apoptotic phenomenon and late onset of neurologic disorders. SN - 1460-9592 UR - https://www.unboundmedicine.com/medline/citation/24725211/Erythropoietin_protects_newborn_rat_against_sevoflurane_induced_neurotoxicity_ L2 - https://doi.org/10.1111/pan.12372 DB - PRIME DP - Unbound Medicine ER -