Delayed increase of astrocytic aquaporin 4 after juvenile traumatic brain injury: possible role in edema resolution?
Traumatic brain injury (TBI) is one of the leading causes of death and disability in children and adolescents. The neuropathological sequelae that result from TBI are a complex cascade of events including edema formation, which occurs more frequently in the pediatric than the adult population. This developmental difference in the response to injury may be related to higher water content in the young brain and also to molecular mechanisms regulating water homeostasis. Aquaporins (AQPs) provide a unique opportunity to examine the mechanisms underlying water mobility, which remain poorly understood in the juvenile post-traumatic edema process. We examined the spatiotemporal expression pattern of principal brain AQPs (AQP1, AQP4, and AQP9) after juvenile TBI (jTBI) related to edema formation and resolution observed using magnetic resonance imaging (MRI). Using a controlled cortical impact in post-natal 17 day-old rats as a model of jTBI, neuroimaging analysis showed a global decrease in water mobility (apparent diffusion coefficient, ADC) and an increase in edema (T2-values) at 1 day post-injury, which normalized by 3 days. Immunohistochemical analysis of AQP4 in perivascular astrocyte endfeet was increased in the lesion at 3 and 7days post-injury as edema resolved. In contrast, AQP1 levels distant from the injury site were increased at 7, 30, and 60 days within septal neurons but did not correlate with changes in edema formation. Group differences were not observed for AQP9. Overall, our observations confirm that astrocyticAQP4 plays a more central role than AQP1 or AQP9 during the edema process in the young brain.
Department of Physiology, Loma Linda University, Loma Linda, CA 92354, USA.
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Fukuda
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Pop
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Spagnoli
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Ashwal
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Obenaus
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Badaut
D000818:Animals; D051398:Aquaporin 1 / Q000378:metabolism; D051401:Aquaporin 4 / Q000378:metabolism*; D020346:Aquaporins / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism*; D015153:Blotting, Western; D001929:Brain Edema / Q000378:metabolism* / Q000503:physiopathology*; D001930:Brain Injuries / Q000378:metabolism* / Q000503:physiopathology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
C496022:Aqp1 protein, rat; C496032:Aqp4 protein, rat; C491637:Aqp9 protein, rat; D051401:Aquaporin 4; D020346:Aquaporins; D005904:Glial Fibrillary Acidic Protein; D051398:Aquaporin 1