Differential upregulation of aquaporin-4 mRNA expression in reactive astrocytes after brain injury: potential role in brain edema.
Astrocytes and aquaporin-4 (AQP4) play a significant role in brain ion homeostasis. Consequently the regulation of AQP4 mRNA in the CNS after different neurological insults was of interest. A single intrastriatal injection of ringer or quinolinic acid strongly induced AQP4 mRNA in the striatum, specially at the core of the lesion. Colocalization studies demonstrated that AQP4 mRNA induction was restricted to hypertrophic astrocytes. The extent of striatal AQP4 mRNA induction did not correlate with neuronal degeneration, but it did with extravasation of Evans blue dye as a marker of BBB disruption. Distant lesions were additionally induced by either 6-OHDA or a knife cut in the medial forebrain bundle (MFB). The former, but not the latter, induced a high AQP4 mRNA expression in the lesioned substantia nigra. However, axotomy of the MFB induced a high AQP4 mRNA expression at the lesion site. We conclude that the induction of AQP4 mRNA expression is related to disruption of the blood-brain barrier and under brain edema conditions this water channel plays a key role in the reestablishment of the brain osmotic equilibrium.
Vizuete
M L
ML
Departamento de Bioquímica, Bromatología, Toxicología y Medicina Legal, Facultad de Farmacia, Calle Profesor García González s/n, Sevilla, 41012, Spain. mvizuete@cica.es
Venero
J L
JL
Vargas
C
C
Ilundáin
A A
AA
Echevarría
M
M
Machado
A
A
Cano
J
J
D000818:Animals; D051401:Aquaporin 4; D020346:Aquaporins / Q000096:biosynthesis* / Q000502:physiology; D001253:Astrocytes / Q000378:metabolism*; D019771:Axotomy; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D001929:Brain Edema / Q000378:metabolism*; D001930:Brain Injuries / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016627:Oxidopamine / Q000633:toxicity; D017378:Quinolinic Acid / Q000633:toxicity; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000187:drug effects
C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D020346:Aquaporins; D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D016627:Oxidopamine; D017378:Quinolinic Acid