Reversal of behavioral changes in rats subjected to portacaval shunt with oral neomycin therapy

Hari S. Conjeevaram, Alexander Nagle, Andrew Katz, Kristine Kaminsky‐Russ, Arthur J. McCullough, Kevin D. Mullen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

The portacaval shunt rat is often used as a model of human portal‐systemic encephalopathy, but its relevance to human portal‐systemic encephalopathy remains uncertain. Specifically, it has not been demonstrated that the behavioral changes seen in this model respond to measures known to improve portal‐systemic encephalopathy in human subjects. Accordingly, the aim of this study was to establish whether neomycin (an effective treatment for portal‐systemic encephalopathy in human beings) added to the drinking water of rats subjected to portacaval shunt reversed or ameliorated the reduction in spontaneous motor activity, which represents a measure of encephalopathy in this animal model. A randomized, placebocontrolled crossover design was used, with each animal serving as its own control. After establishment of baseline activities, 12 rats with portacaval shunt and 12 sham‐operated rats were divided into two equal groups: Group A animals received neomycin for 1 wk; this was followed by 1 wk off neomycin; in group B rats, the sequence was reversed. Spontaneous intake of neomycin for 7 days at doses comparable to human usage (0.1 to 0.2 gm/kg/day) was associated with a significant increase in spontaneous motor activity in rats subjected to portacaval shunt (26.4% in group A, 66.3% in group B; p<0.01 for each protocol) with no significant effect in sham‐operated animals. Withdrawal of neomycin resulted in reversal of this effect in group A rats subjected to portacaval shunt. Similar significant improvements for exploratory activity as measured on the basis of nose‐hole pokes was also seen in rats subjected to portacaval shunt and given neomycin. These neomycin‐associated changes in the motor activity of rats subjected to portacaval shunt could not be attributed to any effect of neomycin on serum ammonia level. These findings support the concept that the rat subjected to portacaval shunt is a valid model of human portal‐systemic encephalopathy that can be used to explore the pathophysiology of this syndrome. (HEPATOLOGY 1994;19:1245–1250.)

Original languageEnglish (US)
Pages (from-to)1245-1250
Number of pages6
JournalHepatology
Volume19
Issue number5
DOIs
StatePublished - May 1994

ASJC Scopus subject areas

  • Hepatology

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