title: Large-dose pretreatment with methylprednisolone fails to attenuate neuronal injury after deep hypothermic circulatory arrest in a neonatal piglet model.
abstract: Conflicting results have been reported with regard to the neuroprotective effects of steroid treatment with cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). We evaluated the mode and severity of neuronal cell injury in neonatal piglets after prolonged DHCA and the possible neuroprotective effect of systemic pretreatment (>6 h before surgery) with large-dose methylprednisolone (MP). Nineteen neonatal piglets (age, <10 days; weight, 2.1 +/- 0.5 kg) were randomly assigned to 2 groups: 7 animals were pretreated with large-dose systemic MP (30 mg/kg) 24 h before surgery, and 12 animals without pharmacological pretreatment (saline) served as control groups. All animals were connected to full-flow CPB with cooling to 15 degrees C and 120 min of DHCA. After rewarming to 38.5 degrees C with CPB, animals were weaned from CPB and survived 6 h before they were killed, and the brain was prepared for light and electron microscopy, immunohistochemistry, and TUNEL-staining. Quantitative histological studies were performed in hippocampus, cortex, cerebellum, and caudate nucleus. Systemic pretreatment with large-dose MP lead to persistent hyperglycemia but no significant changes of cerebral perfusion. Necrotic and apoptotic neuronal cell death were detected in all analyzed brain regions after 120 min of DHCA. In comparison to the control group, large-dose pretreatment with systemic MP lead to an increase of necrotic neuronal cell death and induced significant neuronal apoptosis in the dentate gyrus of the hippocampus (P = 0.001). In conclusion, systemic pretreatment with large-dose MP fails to attenuate neuronal cell injury after prolonged DHCA and induces regional neuronal apoptosis in the dentate gyrus.
authors.affiliation: Departments of *Paediatric Cardiology and Congenital Heart Disease, †Anesthesiology, and ‡Thoracic and Cardiovascular Surgery, Deutsches Herzzentrum Berlin; §Department of Neuropathology, University Clinic Benjamin Franklin, Free University of Berlin; and ∥Animal Experimental Laboratory, Charité, Humboldt University, Berlin, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Schubert
authors.forename: Gisela
authors.initials: G
authors.lastname: Stoltenburg-Didinger
authors.forename: Anke
authors.initials: A
authors.lastname: Wehsack
authors.forename: Dirk
authors.initials: D
authors.lastname: Troitzsch
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Boettcher
authors.forename: Michael
authors.initials: M
authors.lastname: Huebler
authors.forename: Matthias
authors.initials: M
authors.lastname: Redlin
authors.forename: Majid
authors.initials: M
authors.lastname: Kanaan
authors.forename: Michael
authors.initials: M
authors.lastname: Meissler
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lange
authors.forename: Hashim
authors.initials: H
authors.lastname: Abdul-Khaliq
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001786:Blood Glucose / Q000032:analysis; D002560:Cerebrovascular Circulation / Q000187:drug effects; D006324:Heart Arrest, Induced / Q000009:adverse effects*; D007036:Hypothermia, Induced / Q000009:adverse effects*; D008775:Methylprednisolone / Q000494:pharmacology*; D009474:Neurons / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D013552:Swine
chemical_list: D001786:Blood Glucose; D018696:Neuroprotective Agents; D008775:Methylprednisolone