Rats with minimal hepatic encephalopathy due to po

Authors: Ana Agusti Jennifer L Dziedzic Vicente HernandezRabaza Tomas R Guilarte Vicente Felipo

Publish Date: 2013/12/04

Volume: 29, Issue: 4, Pages: 955-963

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Abstract

Neuroinflammation plays a main role in neurological deficits in rats with minimal hepatic encephalopathy MHE due to portacaval shunt PCS Treating PCS rats with SB239063 an inhibitor of MAPkinasep38 reduces microglial activation and brain inflammatory markers and restores cognitive and motor function The translocator protein18kDa TSPO is considered a biomarker of neuroinflammation TSPO is increased in brain of PCS rats and of cirrhotic patients that died in hepatic coma Rats with MHE show strong microglial activation in cerebellum and milder in other areas when assessed by MHCII immunohistochemistry This work aims were assessing 1 whether binding of TSPO ligands is selectively increased in cerebellum in PCS rats 2 whether treatment with SB239063 reduces binding of TSPO ligands in PCS rats 3 which cell type microglia astrocytes increases TSPO expression Quantitative autoradiography was used to assess TSPOselective 3HRPK11195 binding to different brain areas TSPO expression increased differentially in PCS rats reaching mild expression in striatum or thalamus and very high levels in cerebellum TSPO was expressed in astrocytes and microglia Treatment with SB239063 did not reduces 3HPK11195 binding in PCS rats SB239063 reduces microglial activation and levels of inflammatory markers but not binding of TSPO ligands This indicates that SB239063induced neuroinflammation reduction in PCS rats is not mediated by effects on TSPO Also enhanced TSPO expression is not always associated with cognitive or motor deficits If enhanced TSPO expression plays a role in mechanisms leading to neurological alterations in MHE SB239063 would interfere these mechanisms at a later stepBinding of 3HPK11195 in different regions of neuroanatomical level 2 of control and PCS rats treated or not with the inhibitor of p38 SB239063 A Shows representative autoradiography images for each group B Shows the quantification of the binding of 3HPK11195 in the same regions shown in Fig 2 Values are the mean ± SEM of the number of rats indicated in Table 1 for each group SM = control rats with “sham” operation treated with vehicle SM + SB = control rats with “sham” operation and treated with SB239063 PCS = PCS rats treated with vehicle PCS + SB = PCS rats treated with SB239063 JPEG 148 kbBinding of 3HPK11195 in different regions of neuroanatomical level 3 of control and PCS rats treated or not with the inhibitor of p38 SB239063 A Shows representative autoradiography images for each group B Shows the quantification of the binding of 3HPK11195 in the same regions shown in Fig 2 Values are the mean ± SEM of the number of rats indicated in Table 1 for each group SM = control rats with “sham” operation treated with vehicle SM + SB = control rats with “sham” operation and treated with SB239063 PCS = PCS rats treated with vehicle PCS + SB = PCS rats treated with SB239063 JPEG 146 kbBinding of 3HPK11195 in different regions of neuroanatomical level 4 of control and PCS rats treated or not with the inhibitor of p38 SB239063 A Shows representative autoradiography images for each group B Shows the quantification of the binding of 3HPK11195 in the same regions shown in Fig 2 Values are the mean ± SEM of the number of rats indicated in Table 1 for each group SM = control rats with “sham” operation treated with vehicle SM + SB = control rats with “sham” operation and treated with SB239063 PCS = PCS rats treated with vehicle PCS + SB = PCS rats treated with SB239063 JPEG 144 kb

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