J.M. Simard

University of Maryland, Baltimore, Baltimore, MD, United States

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Publications (2)4.38 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Brain edema is a serious complication of hepatic encephalopathy associated with fulminant hepatic failure (FHF). Factors responsible for such swelling are not clear, but ammonia, a toxin strongly implicated in FHF, is known to induce astrocyte swelling. The mechanism(s) responsible for ammonia-induced swelling, however, are not known. Aquaporins are plasma membrane proteins that mediate transmembrane water movement. To investigate the potential role of aquaporins in astrocyte swelling, we measured aquaporin-4 (AQP-4) protein expression in cultured astrocytes exposed to 5 mM NH4Cl. AQP-4 levels significantly increased 10 h after treatment with ammonia, and displayed a progressive rise up to 48 h, which appeared to precede the onset of astrocyte swelling. AQP-4 may be involved in the astrocyte swelling associated with hyperammonemic states.
    Neuroreport 01/2004; 14(18):2379-82. · 1.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Brain edema is a serious complication of hepatic encephalopathy associated with fulminant hepatic failure (FHF). A major component of the edema seems to be cytotoxic, involving astrocyte swelling. Although the mechanism of brain edema in FHF is incompletely understood, it is generally believed that ammonia is involved critically in this process. Recent studies have shown that exposure of cultured astrocytes to ammonia results in the mitochondrial permeability transition (MPT), a phenomenon associated with mitochondrial failure and subsequent cellular dysfunction. The present study examined the potential role of the MPT in the astrocyte swelling associated with ammonia toxicity. Treatment of cultured astrocytes with ammonia (5 mM) caused a time-dependent increase in astrocyte cell volume (swelling), which was completely inhibited by the MPT inhibitor cyclosporin A (CsA). In this study, CsA also inhibited the ammonia-induced aquaporin 4 (AQP4) upregulation, which had been shown previously to be increased in cultured astrocytes by ammonia treatment. These findings suggest that the MPT plays a significant role in the ammonia-induced astrocyte swelling and may contribute to the brain edema associated with FHF. © 2003 Wiley-Liss, Inc.
    Journal of Neuroscience Research 12/2003; 74(6):891 - 897. · 2.97 Impact Factor

Publication Stats

84 Citations
4.38 Total Impact Points

Institutions

  • 2003
    • University of Maryland, Baltimore
      • Department of Surgery
      Baltimore, MD, United States