What is the role of neurosteroids in the pathogenesis of hepatic encephalopathy (HE)?

Updated: Apr 04, 2019
  • Author: David C Wolf, MD, FACP, FACG, AGAF, FAASLD; Chief Editor: BS Anand, MD  more...
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Answer

Answer

The neuronal GABA receptor complex contains a binding site for neurosteroids. Some investigators contend that neurosteroids play a key role in hepatic encephalopathy. [1]

In experimental models, neurotoxins, like ammonia and manganese, increase the production of the peripheral-type benzodiazepine receptor (PTBR) in astrocytes. [20] PTBR, in turn, stimulates the conversion of cholesterol to pregnenolone to neurosteroids. Neurosteroids are then released from the astrocytes. They are capable of binding to their receptor within the neuronal GABA receptor complex and can increase inhibitory neurotransmission.

One study compared the levels of various chemicals in the autopsied brain tissues from patients with cirrhosis who had either died in hepatic coma or died without evidence of hepatic encephalopathy. Elevated levels of allopregnanolone, the neuroactive metabolite of pregnenolone, were found in the brain tissue of patients who died in hepatic coma. [21] Brain levels of benzodiazepine receptor ligands were not significantly elevated in patients with or without coma. This work further bolsters the role of neurosteroids in hepatic encephalopathy.


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