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J Neurotrauma. 2018 Feb 15;35(4):671-680. doi: 10.1089/neu.2017.5015. Epub 2018 Jan 11.

Erythropoietin Attenuates the Brain Edema Response after Experimental Traumatic Brain Injury.

Author information

1
1 Perioperative Medicine and Intensive Care, Karolinska University Hospital, Karolinska Institutet , Stockholm, Sweden .
2
2 Department of Physiology and Pharmacology, Karolinska University Hospital, Karolinska Institutet , Stockholm, Sweden .
3
3 Department of Women's and Children's Health Karolinska University Hospital, Karolinska Institutet , Stockholm, Sweden .

Abstract

Erythropoietin (EPO) has neuroprotective effects in multiple central nervous system (CNS) injury models; however EPO's effects on traumatic brain edema are elusive. To explore EPO as an intervention in traumatic brain edema, male Sprague-Dawley (SD) rats were subjected to blunt, controlled traumatic brain injury (TBI). Animals were randomized to EPO 5000 IU/kg or saline (control group) intraperitoneally within 30 min after trauma and once daily for 4 consecutive days. Brain MRI, immunohistofluorescence, immunohistochemistry, and quantitative protein analysis were performed at days 1 and 4 post- trauma. EPO significantly prevented the loss of the tight junction protein zona occludens 1 (ZO-1) observed in control animals after trauma. The decrease of ZO-1 in the control group was associated with an immunoglobulin (Ig)G increase in the perilesional parenchyma, indicating blood-brain barrier (BBB) dysfunction and increased permeability. EPO treatment attenuated decrease in apparent diffusion coefficient (ADC) after trauma, suggesting a reduction of cytotoxic edema, and reduced the IgG leakage, indicating that EPO contributed to preserve BBB integrity and attenuated vasogenic edema. Animals treated with EPO demonstrated conserved levels of aquaporin 4 (AQP4) protein expression in the perilesional area, whereas control animals showed a reduction of AQP4. We show that post TBI administration of EPO decreases early cytotoxic brain edema and preserves structural and functional properties of the BBB, leading to attenuation of the vasogenic edema response. The data support that the mechanisms involve preservation of the tight junction protein ZO-1 and the water channel AQP4, and indicate that treatment with EPO may have beneficial effects on the brain edema response following TBI.

KEYWORDS:

BBB; EPO; TBI; aquaporin; brain edema

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