@misc{,
 copyright={Creative Commons Attribution BY 4.0 license},
 address={Warszawa},
 howpublished={online},
 abstract={Hepatic encephalopathy (HE) is a neuropsychiatric disorder, which is usually caused by liver failure. As a result of hepatocellular dysfunctions, various neurotoxic compounds acumulate in the blood, from whih ammonia plays main role in the development of disease. Acute from of HE is characterized by rapid worsening of clinical symptoms, among which the most serious are: neurotransmission disorders , which in the late stages of the disease may manifest as convulsions or coma and brain edema, whoch may result in the patient's death. The neurotoxicity of ammonia is associated with changes in glutamatergic neurotransmission and with excessive production of glutamine (Gln) in astrocytes. Due to Gln osmotic properties its accumulation in the cells causes osmotic imbalance and the formation of cytotoxic component of cerebral edema. The accumulation of Gln in astrocytes may be caused by glutamine transport distrurbances. SN1 is the most important protein that regulates Gln transport out from astrocytes. The decrease of SN1 protein level was observed in the brain of rats with acutr HE induced by thioacetamide. The hypothesis assumr participation of the astrocytic SN1transporter in the retention of Gln in cells , which contributes to the occurrence of cytotoxic brain edema and glutamatergic neurotransmission disorders, twp clinically most seriosvsymptoms of acute HE. In the study we used two animal models, first was mice model of acute liver failure induced by azoxymethane (AOM) injection, and second was model using the vivo-morpholino technique based on local SN1 protein silencing. The mouse AOM model of acute HE reflects the characteristics of the symptomatic stage of acute HE in patients. Two main clinical manfestations, such as neurotransmission impairement (behavarioral and electrophysiological studies) and the occurence of both components of cerebral edema ( ultrastructure analysis, MRI technique, and 1H NMR) have been demonstrated. Reduction of the SN1protein expression and functional changes of the Gln transport suggest the role of the SN1 transporter in the observed clinical symptoms. Local silencing of the transporter by the vivo-morholino method resulted in the occurence of a cytotoxic component of brain edema (MRI, 1H NMR and extracellular measuremen of amino acids). In addition, the subtle changes in electrophysiological parametres documented the role of the SN! transporter in maintaning of glutamatergic transmission. The results of the study indicate the role of the Gln transport via the astrocytic Gln transporter SN1 in AOM-induced astrocytic and neural dysfunction.},
 type={Text},
 URL={http://rcin.org.pl/Content/68262/PDF/DOKTORAT_Popek.pdf},
 keywords={Hepatic Encephalopathy},
}