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. 2010-08-01; 68(2): 123-127
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1. Pediatr Res. 2010 Aug;68(2):123-7. doi: 10.1203/00006450-201011001-00237.
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.
Brissaud O(1), Villega F, Pieter Konsman J, Sanchez S, Raffard G, Franconi JM,
Chateil JF, Bouzier-Sore AK.
(1)Neonatal Intensive Care Unit, University Children’s Hospital, Bordeaux 33076,
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.
PMID: 20461024 [Indexed for MEDLINE]