Influence of albumin dialysis (MARS) on neuronal network activity in vitro

In liver failure, toxic substances accumulate in the body that may disturb the function of the central nervous system. This is generally thought to result in hepatic encephalopathy and coma. A new dialysis treatment based on albumin dialysis (Molecular Adsorbents Recirculating System, MARS) was developed to remove these substances from the patients.

AIM: In vivo, the degree of hepatic encephalopathy does not always correlate with plasma concentrations of potential toxins. We investigated the reaction of spontaneously active neuronal networks in vitro to ultrafiltrates of human blood plasma to determine if such toxins can be detected with this system, and if so, to evaluate the effect of MARS treatments on the network responses.

METHODS: Dissociated frontal cortex tissue from mouse embryos was cultured and maintained on electrode array plates containing 64 microelectrodes in a 1 mm² area according to the methods of Gross (1994). Previous work has demonstrated the specificity and reversibility of network responses to neurotransmitters and a variety of neuroactive compounds.

RESULTS: Plasma ultrafiltrates from healthy humans caused only minor changes of network activity. In contrast, severe changes were generally evoked by samples from patients in hepatic coma (stage II-III). After a single MARS treatment of the patients (6 hours duration), effects were much less pronounced. Moreover, several MARS treatments on subsequent days led to network responses close to the effect of samples from healthy subjects. This was in accordance to marked clinical improvement of the patients. Neuronal responses were highly reproducible on the same as well as on different networks.

CONCLUSIONS: MARS treatments may be beneficial to the improvement of cerebral function in hepatic encephalopathy. The biosensor assay introduced by us may be a means to monitor the toxic load of the plasma in patients with liver failure and to integrate the effects of different compounds in plasma onto neuronal and nervous system function.