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Indomethacin improves locomotor deficit and reduces brain concentrations of neuroinhibitory steroids in rats following portacaval anastomosis

, : Indomethacin improves locomotor deficit and reduces brain concentrations of neuroinhibitory steroids in rats following portacaval anastomosis. Neurogastroenterology and Motility 20(8): 949-957

Hepatic encephalopathy (HE) is a neuropsychiatric complication of both acute and chronic liver failure characterized by progressive neuronal inhibition. Some neurosteroids are potent positive allosteric modulators of the gamma-aminobutyric acid (GABA)-A receptor complex, and 'increased GABAergic tone' has been proposed to explain the neuroinhibition characteristics of HE. Brain levels of the neurosteroids pregnenolone, allopregnanolone and tetrahydrodesoxycorticosterone (THDOC) and the functional status of the GABA-A receptor complex were assessed in rats following portacaval anastomosis (PCA). Effects of indomethacin, an inhibitor of the 3alpha-hydroxysteroid dehydrogenase enzyme involved in neurosteroid synthesis, on PCA rat locomotor activity and brain neurosteroid levels were also assessed. Significant increases of the neurosteroid pregnenolone (2.6-fold), allopregnanolone (1.7-fold) and THDOC (4.7-fold) were observed in brains of PCA rats. Brain levels of these neurosteroids were in the nanomolar range, sufficient to exert positive allosteric modulatory effects at the GABA-A receptor. Indomethacin (0.1-5 mg kg(-1)) ameliorated dose-dependently the locomotor deficit of PCA rats and concomitantly normalized brain levels of allopregnanolone and THDOC. Increased brain levels of neurosteroids with positive allosteric modulatory actions at the neuronal GABA-A receptor offer a cogent explanation for the notion of 'increased GABAergic tone' in HE. Pharmacological approaches using agents that either reduce neurosteroid synthesis or modulate the neurosteroid site on GABA-A receptor could offer new therapeutic tools for the management and treatment of HE.


PMID: 18482252

DOI: 10.1111/j.1365-2982.2008.01132.x

Other references

Kirby, P., 1992: Trigonocranus emmeae Fieber (Hemiptera: Cixiidae) in Northamptonshire. British Journal of Entomology and Natural History, 54: 183

Sinzinger, H., 1985: Double blind study of the influence of co-dergocrine on platelet parameters in healthy volunteers. In 20 healthy volunteers double-blind randomized study was done to examine the effect of co-dergocrine (Hydergine) on platelet function. All the volunteers were pretreated with 3 X 1 placebo for 1 week, followed by the randomized study in which 10...

Riekstniece E.; White J.I., 1974: Iodine 131 uptake and serum levels of growth hormone after interstrain thyroid transplants in rats. Federation Proceedings 33(3 PART 1): 250

Montenovo, M.I.; Jalikis, F.G.; Li, M.; Yeh, M.; Dick, A.; Hansen, R.; Reyes, J.D., 2016: Superior Patient and Graft Survival in Adult Liver Transplant with Rabbit Antithymocyte Globulin Induction: Experience with 595 Patients. The use of induction therapy in liver transplant is debatable. We aimed to compare clinical outcomes of different induction protocols in liver transplant recipients. This was a retrospective cohort analyses using the University of Washington Trans...

Ylikorkala, O.; Jouppila, P.; Kirkinen, P.; Viinikka, L., 1984: Maternal thromboxane, prostacyclin, and umbilical blood flow in humans. The stable hydration products of the vasoconstrictory and proaggregatory thromboxane A2 and vasodilatory and antiaggregatory prostacyclin, ie, thromboxane B2 and 6-keto-prostaglandin F1a, respectively, were measured with radioimmunoassays from 67...

Okła, K.; Wertel, I.; Polak, G.; Surówka, J.; Wawruszak, A.; Kotarski, J., 2016: Tumor-Associated Macrophages and Myeloid-Derived Suppressor Cells as Immunosuppressive Mechanism in Ovarian Cancer Patients: Progress and Challenges. NlmCategory="UNASSIGNED">Cancers are complex masses of malignant cells and nonmalignant cells that create the tumor microenvironment (TME). Non-transformed cells of the TME such as tumor-associated macrophages (TAMs) and myeloid-deriv...

Miller, R.S.; Thompson, M.Lou.; Williams, M.A., 2007: Trimester-specific blood pressure levels in relation to maternal pre-pregnancy body mass index. We evaluated the influence of maternal pre-pregnancy body mass index (BMI), based on reported pre-pregnancy weight and height, on blood pressure (BP) levels during pregnancy by using information from a prospective cohort of 1733 women recruited be...

Leroi B.; Chararas C.; Chipoulet J.M., 1984: Study of glycosidase activities of the digestive tract of the larvae and adults in acanthoscelides obtectus coleoptera bruchidae. Adults and larvae of A. obtectus eat 2 different types of food, similar in carbohydrate composition: larvae eat seeds of Phaseolus vulgaris and P. coccineus, adults eat principally pollen of various plants. The digestive activity of larvae and adu...

Montagne, A.; Toga, A.W.; Zlokovic, B.V., 2016: Blood-Brain Barrier Permeability and Gadolinium: Benefits and Potential Pitfalls in Research. JAMA Neurology 73(1): 13-14

Paykel, E.S.; Brugha, T.; Fryers, T., 2005: Size and burden of depressive disorders in Europe. We review epidemiological studies of depression in Europe. Community surveys are essential. Methodological differences in survey methods, instruments, nuances in language and translation limit comparability, but consistent findings are emerging. W...