AUTHOR=Mendes Renata de S. , Martins Gloria , Oliveira Milena V. , Rocha Nazareth N. , Cruz Fernanda F. , Antunes Mariana A. , Abreu Soraia C. , Silva Adriana L. , Takiya Christina , Pimentel-Coelho Pedro M. , Robba Chiara , Mendez-Otero Rosália , Pelosi Paolo , Rocco Patricia R. M. , Silva Pedro L. 

TITLE=Iso-Oncotic Albumin Mitigates Brain and Kidney Injury in Experimental Focal Ischemic Stroke

JOURNAL=Frontiers in Neurology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.01001

DOI=10.3389/fneur.2020.01001

ISSN=1664-2295

ABSTRACT=<p><bold>Background:</bold> There is widespread debate regarding the use of albumin in ischemic stroke. We tested the hypothesis that an iso-oncotic solution of albumin (5%), administered earlier after acute ischemic stroke (3 h), could provide neuroprotection without causing kidney damage, compared to a hyper-oncotic albumin (20%) and saline.</p><p><bold>Objective:</bold> To compare the effects of saline, iso-oncotic albumin, and hyper-oncotic albumin, all titrated to similar hemodynamic targets, on the brain and kidney.</p><p><bold>Methods:</bold> Ischemic stroke was induced in anesthetized male Wistar rats (<italic>n</italic> = 30; weight 437 ± 68 g) by thermocoagulation of pial blood vessels of the primary somatosensory, motor, and sensorimotor cortices. After 3 h, animals were anesthetized and randomly assigned (<italic>n</italic> = 8) to receive 0.9% NaCl (Saline), iso-oncotic albumin (5% ALB), and hyper-oncotic albumin (20% ALB), aiming to maintain hemodynamic stability (defined as distensibility index of inferior vena cava &lt;25%, mean arterial pressure &gt;80 mmHg). Rats were then ventilated using protective strategies for 2 h. Of these 30 animals, 6 were used as controls (focal ischemic stroke/no fluid).</p><p><bold>Results:</bold> The total fluid volume infused was higher in the Saline group than in the 5% ALB and 20% ALB groups (mean ± SD, 4.3 ± 1.6 <italic>vs</italic>. 2.7 ± 0.6 and 2.6 ± 0.5 mL, <italic>p</italic> = 0.03 and <italic>p</italic> = 0.02, respectively). The total albumin volume infused (g/kg) was higher in the 20% ALB group than in the 5% ALB group (1.4 ± 0.6 <italic>vs</italic>. 0.4 ± 0.2, <italic>p</italic> &lt; 0.001). Saline increased neurodegeneration (Fluoro-Jade C staining), brain inflammation in the penumbra (higher tumor necrosis factor-alpha expression), and blood-brain barrier damage (lower gene expressions of claudin-1 and zona occludens-1) compared to both iso-oncotic and hyper-oncotic albumins, whereas it reduced the expression of brain-derived neurotrophic factor (a marker of neuroregeneration) compared only to iso-oncotic albumin. In the kidney, hyper-oncotic albumin led to greater damage as well as higher gene expressions of kidney injury molecule-1 and interleukin-6 than 5% ALB (<italic>p</italic> &lt; 0.001).</p><p><bold>Conclusions:</bold> In this model of focal ischemic stroke, only iso-oncotic albumin had a protective effect against brain and kidney damage. Fluid therapy thus requires careful analysis of impact not only on the brain but also on the kidney.</p>