کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2201746 1551318 2008 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The neurosteroid system: Implication in the pathophysiology of hepatic encephalopathy
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
The neurosteroid system: Implication in the pathophysiology of hepatic encephalopathy
چکیده انگلیسی

Hepatic encephalopathy (HE) is a serious cerebral complication of both acute and chronic liver failure. In acute liver failure, astrocytes undergo swelling which results in increased intracranial pressure and may lead to brain herniation and death. In chronic liver failure, Alzheimer-type II astrocytosis is the characteristic neuropathologic finding. Patients with liver failure manifest severe alterations of their quality of life including sleep disorders as well as memory, learning, and locomotor abnormalities. Neurosteroids (NS) are synthesized in the brain mainly by astrocytes independent of peripheral steroidal sources (adrenals and gonads) and are suggested to play a role in the pathogenesis of HE. NS bind and modulate different types of neural receptors; effects on the gamma amino butyric acid (GABA)-A receptor complex are the most extensively studied. For example, the NS tetrahydroprogesterone (allopregnanolone), and tetrahydrodeoxycorticosterone (THDOC) are potent positive allosteric modulators of the GABA-A receptor. As a consequence of modulation of these receptors, NS stimulate inhibitory neurotransmission in the CNS, and neuroinhibitory changes including “increased GABA-ergic tone” have been suggested as pathophysiological mechanisms in HE. Moreover, some NS bind to intracellular receptors through which they also regulate gene expression, and there is substantial evidence confirming that expression of genes coding for key astrocytic and neuronal proteins are altered in HE. This review summarizes findings consistent with the involvement of NS in human and experimental HE.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurochemistry International - Volume 52, Issues 4–5, March–April 2008, Pages 575–587
نویسندگان
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