Erythropoietin attenuates post-traumatic injury in organotypic hippocampal slices.
Recent experimental evidence indicates that erythropoietin (Epo), in addition to its hormonal role in regulating red cell production, operates as a neuroprotective agent. So far, the neuroprotective effect of human recombinant Epo (rhEpo) has been mainly demonstrated in models of cerebral ischemia/hypoxia and in selected in vivo studies of traumatic neuronal injury. To further investigate the potential role of this multifunctional trophic factor in post-traumatic cell death, we examined the protective effects of rhEpo in a newly developed model of mechanical trauma in organotypic hippocampal slices. Organotypic rat hippocampal slices were subjected to traumatic injury by allowing a stylus to impact on the CA1 area with an energy of 6 microJ. Hippocampal damage was identified and measured 24 and 48 h later with the fluorescent dye propidium iodide (PI). In untreated slices, the impact induced a significant increase in the mean hippocampal PI fluorescence, co-localized with the area of impact at 24 h (primary post-traumatic injury) and progressively spread to the whole slice between 24 and 48 h (secondary post-traumatic injury). Addition of rhEpo (1-100 UI/mL) or of the NMDA antagonist MK-801 (30 microM) immediately after the traumatic injury reduced hippocampal damage by approximately 30% when observed 24 h later. At 48 h after trauma, the protective effect of rhEpo was greater (by about 47%) and significantly more pronounced than that of MK-801 (28%). Our results suggest that the neuroprotective activity of rhEpo is particularly effective against delayed, secondary post-traumatic damage. This well tolerated agent could provide a therapeutic benefit in pathologies involving post-traumatic neurodegeneration.
Dipartimento di Area Critica Medico Chirurgica, Sezione di Anestesiologia e Terapia Intensiva, Università di Firenze, Firenze, Italy. chiara.adembri@unifi.it
Chiara
C
Adembri
Annalisa
A
Bechi
Elena
E
Meli
Elena
E
Gramigni
Luna
L
Venturi
Flavio
F
Moroni
A Raffaele
AR
De Gaudio
Domenico E
DE
Pellegrini-Giampietro
D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004921:Erythropoietin / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000293:injuries* / Q000503:physiopathology; D066298:In Vitro Techniques; D008954:Models, Biological; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D011419:Propidium; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use; D011994:Recombinant Proteins; D016896:Treatment Outcome
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D004921:Erythropoietin; D011419:Propidium; D016291:Dizocilpine Maleate