Mechanisms of acute uremic encephalopathy: early activation of Fos and Fra-2 gene products in different nuclei/areas of the rat brain.
High levels of various uremic toxins such as guanidino compounds and advanced glycation endproducts, as well as an excess of parathyroid hormones, are involved in the pathogenesis of acute uremic encephalopathy. Moreover, distant effects of the damaged kidney with enhanced production of inflammatory mediators are implicated. Data on the pump activity of an abnormal Na-K-ATPase and inhibition of the organic anion transporter system in the brain have been published previously. Recently, the effect of an experimentally induced acute renal failure (ARF) on the neuronal cell activation of Fos and Fra-2 in the rat brain was investigated by immunohistochemistry. ARF was induced by using the following 3 rat models: bilateral nephrectomy, bilateral ureter ligation, and uranyl acetate injection with corresponding controls. The Fos and the Fra-2 immunoreactive neurons of the brain were determined in a total of 120 brain areas over a period of 3 days post bilateral nephrectomy and bilateral ureter ligation and 12 days after uranyl acetate. An activation response was observed in 73 of 120 areas of the brain. The responses were classified into 4 groups: (1) biogenic amines (noradrenaline, adrenaline, histamine, and 5-hydroxytryptamine), (2) stress-sensitive forebrain areas, (3) neuronal cell groups involved in the regulation of water and electrolyte homeostasis, and (4) central autonomic cell groups. In the uranyl acetate-induced ARF, activation of Fos and Fra-2 immunoreactivity took place at the earliest time-point (3 hours) which persisted even after improvement of ARF. This suggests the involvement of the toxic effects of uranium as a result of its accumulation in the brain.
Heidland
August
A
Department of Internal Medicine, University of Wuerzburg, Wuerzburg, Germany. August.Heidland@t-online.de
Sebekova
Katarina
K
Klassen
André
A
Palkovits
Miklós
M
D058186:Acute Kidney Injury / Q000150:complications / Q000503:physiopathology; D000818:Animals; D001341:Autonomic Nervous System / Q000503:physiopathology; D015306:Biogenic Monoamines / Q000378:metabolism; D001927:Brain Diseases / Q000209:etiology* / Q000503:physiopathology; D051921:Fos-Related Antigen-2 / Q000032:analysis / Q000502:physiology*; D007150:Immunohistochemistry; D009474:Neurons / Q000737:chemistry / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000502:physiology*; D051381:Rats; D013312:Stress, Physiological; D014511:Uremia / Q000150:complications*; D014882:Water-Electrolyte Balance / Q000502:physiology
D015306:Biogenic Monoamines; D051921:Fos-Related Antigen-2; D016760:Proto-Oncogene Proteins c-fos