No neuroprotective effect of erythropoietin under clinical treatment conditions in a rabbit model of Escherichia coli meningitis.
Despite effective antibiotic treatment, neuronal injury is frequent among children and adults with bacterial meningitis resulting in a high rate of death and neurologic sequelae. The hematopoietic cytokine erythropoietin (EPO) provides neuroprotection in models of acute and chronic neurologic diseases. We studied whether recombinant EPO (rEPO) reduces neuronal damage in a rabbit model of Escherichia coli meningitis. Inflammation within the central nervous system (CNS) was monitored by measurement of bacterial load, pleocytosis, protein, and lactate in the cerebrospinal fluid (CSF). Neuronal damage was measured by quantification of the density of apoptotic neurons in the hippocampal dentate gyrus and the concentration of the global neuronal destruction marker neuron-specific enolase (NSE) in CSF. To increase clinical relevance, rEPO was applied as adjunctive therapy from the beginning of antibiotic therapy 12 h after infection. EPO treatment applied as an intravenous injection at a dose of 1000 IU/kg body weight resulted in plasma concentrations of 6993 +/- 1406 mIU/mL, CSF concentrations of 1291 +/- 568 mIU/mL, and a CSF-to-plasma ratio of 0.18 +/- 0.07 (mean +/- SD) 6 h after injection. Under these treatment conditions, no anti-inflammatory or neuroprotective effect of EPO was observed. "
Spreer
Annette
A
Department of Neurology, University Hospital, Georg-August-University of Göttingen, 37075 Göttingen, Germany.
Gerber
Joachim
J
Hanssen
Mareike
M
Nau
Roland
R
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018891:Dentate Gyrus / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D007275:Injections, Intravenous; D020814:Meningitis, Escherichia coli / Q000134:cerebrospinal fluid / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D009422:Nervous System Diseases / Q000134:cerebrospinal fluid / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D010751:Phosphopyruvate Hydratase / Q000134:cerebrospinal fluid; D011817:Rabbits; D011994:Recombinant Proteins; D012720:Severity of Illness Index; D013997:Time Factors
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D004921:Erythropoietin; D010751:Phosphopyruvate Hydratase