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Short-term effect of erythropoietin on brain lesions and aquaporin-4 expression in a hypoxic-ischemic neonatal rat model assessed by magnetic resonance diffusion weighted imaging and immunohistochemistry.
Pediatr Res. 2010 Aug; 68(2):123-7.PR

Abstract

Erythropoietin (Epo) is an endogenous cytokine that regulates hematopoiesis and is widely used to treat anemia. In addition, it has recently increased interest in the neurosciences since the new concept of Epo as a neuroprotective agent has emerged. The potential protective effect of human recombinant Epo (r-hu-Epo) on a hypoxic-ischemic (HI) pup rat model was studied. Cerebral HI was obtained by permanent left carotid artery ligature of pups followed by a 2-h hypoxia. Three hours after carotid occlusion, brain lesions were assessed by magnetic resonance diffusion weighted imaging. Intraperitoneal administration of r-hu-Epo (30,000 U/kg dose) limited both the HI-induced brain lesion area and the decrease in apparent diffusion coefficient (ADC) in the lesion. To identify potential mechanisms underlying the effects of Epo, immunohistochemical detection of caspase-3 and water channel protein aquaporin-4 (AQP4) were performed. No early apoptosis was detected, but up-regulation of AQP4 expression was observed in HI pups that received r-hu-Epo compared with HI animals without treatment. This study demonstrates an early neuroprotective effect of Epo with regard to brain lesion area and ADC values. One possible mechanism of Epo for decreasing brain edema and cellular swelling could be a better clearance of water excess in brain tissue, a process possibly mediated by AQP4.

Authors+Show Affiliations

Neonatal Intensive Care Unit, University Children's Hospital, Bordeaux 33076, France. olivier.brissaud@chu-bordeaux.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20461024

Citation

Brissaud, Olivier, et al. "Short-term Effect of Erythropoietin On Brain Lesions and Aquaporin-4 Expression in a Hypoxic-ischemic Neonatal Rat Model Assessed By Magnetic Resonance Diffusion Weighted Imaging and Immunohistochemistry." Pediatric Research, vol. 68, no. 2, 2010, pp. 123-7.
Brissaud O, Villega F, Pieter Konsman J, et al. Short-term effect of erythropoietin on brain lesions and aquaporin-4 expression in a hypoxic-ischemic neonatal rat model assessed by magnetic resonance diffusion weighted imaging and immunohistochemistry. Pediatr Res. 2010;68(2):123-7.
Brissaud, O., Villega, F., Pieter Konsman, J., Sanchez, S., Raffard, G., Franconi, J. M., Chateil, J. F., & Bouzier-Sore, A. K. (2010). Short-term effect of erythropoietin on brain lesions and aquaporin-4 expression in a hypoxic-ischemic neonatal rat model assessed by magnetic resonance diffusion weighted imaging and immunohistochemistry. Pediatric Research, 68(2), 123-7. https://doi.org/10.1203/00006450-201011001-00237
Brissaud O, et al. Short-term Effect of Erythropoietin On Brain Lesions and Aquaporin-4 Expression in a Hypoxic-ischemic Neonatal Rat Model Assessed By Magnetic Resonance Diffusion Weighted Imaging and Immunohistochemistry. Pediatr Res. 2010;68(2):123-7. PubMed PMID: 20461024.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Short-term effect of erythropoietin on brain lesions and aquaporin-4 expression in a hypoxic-ischemic neonatal rat model assessed by magnetic resonance diffusion weighted imaging and immunohistochemistry. AU - Brissaud,Olivier, AU - Villega,Frédéric, AU - Pieter Konsman,Jan, AU - Sanchez,Stéphane, AU - Raffard,Gérard, AU - Franconi,Jean-Michel, AU - Chateil,Jean-François, AU - Bouzier-Sore,Anne-Karine, PY - 2010/5/13/entrez PY - 2010/5/13/pubmed PY - 2010/10/12/medline SP - 123 EP - 7 JF - Pediatric research JO - Pediatr Res VL - 68 IS - 2 N2 - Erythropoietin (Epo) is an endogenous cytokine that regulates hematopoiesis and is widely used to treat anemia. In addition, it has recently increased interest in the neurosciences since the new concept of Epo as a neuroprotective agent has emerged. The potential protective effect of human recombinant Epo (r-hu-Epo) on a hypoxic-ischemic (HI) pup rat model was studied. Cerebral HI was obtained by permanent left carotid artery ligature of pups followed by a 2-h hypoxia. Three hours after carotid occlusion, brain lesions were assessed by magnetic resonance diffusion weighted imaging. Intraperitoneal administration of r-hu-Epo (30,000 U/kg dose) limited both the HI-induced brain lesion area and the decrease in apparent diffusion coefficient (ADC) in the lesion. To identify potential mechanisms underlying the effects of Epo, immunohistochemical detection of caspase-3 and water channel protein aquaporin-4 (AQP4) were performed. No early apoptosis was detected, but up-regulation of AQP4 expression was observed in HI pups that received r-hu-Epo compared with HI animals without treatment. This study demonstrates an early neuroprotective effect of Epo with regard to brain lesion area and ADC values. One possible mechanism of Epo for decreasing brain edema and cellular swelling could be a better clearance of water excess in brain tissue, a process possibly mediated by AQP4. SN - 1530-0447 UR - https://www.unboundmedicine.com/medline/citation/20461024/Short_term_effect_of_erythropoietin_on_brain_lesions_and_aquaporin_4_expression_in_a_hypoxic_ischemic_neonatal_rat_model_assessed_by_magnetic_resonance_diffusion_weighted_imaging_and_immunohistochemistry_ L2 - https://doi.org/10.1203/PDR.0b013e3181e67d02 DB - PRIME DP - Unbound Medicine ER -