Changes in extracellular action potential detect kainic acid and trimethyltin toxicity in hippocampal slice preparations earlier than do MAP2 density measurements.

In vitro electrophysiological techniques for the assessment of neurotoxicity could have several advantages over other methods in current use, including the ability to detect damage at a very early stage, and could further assist in replacing animal experimentation in vivo. We investigated how an electrophysiological parameter, the extracellularly-recorded compound action potential ("population spike", PS) could be used as a marker of in vitro neurotoxicity in the case of two well-known toxic compounds, kainic acid (KA) and trimethyltin (TMT). We compared the use of this electrophysiological endpoint with changes in immunoreactivity for microtubule-associated protein 2 (MAP2), a standard histological test for neurotoxicity.

Effects of exogenous creatine on population spike amplitude and on postanoxic hyperexcitability in brain slices.

In in vitro rat hippocampal slices, a short period of transient anoxia caused a lasting increase in the amplitude of the compound action potential (population spike, PS) that was evoked in CA1 by stimulation of the Schaffer collaterals. No such increase was seen over a comparable period of time in slices that were not subjected to anoxia. The appearance of such an increase was dependent on the duration of anoxia.

Role of creatine and phosphocreatine in neuronal protection from anoxic and ischemic damage.

Phosphocreatine can to some extent compensate for the lack of ATP synthesis that is caused in the brain by deprivation of oxygen or glucose. Treatment of in vitro rat hippocampal slices with creatine increases the neuronal store of phosphocreatine. In this way it increases the resistance of the tissue to anoxic or ischemic damage.

Electrophysiological effects of sustained delivery of CRF and its receptor agonists in hippocampal slices.

The corticotropin-releasing factor (CRF) is a hypothalamic peptide that regulates the release of adrenocorticotropic hormone (ATCH) and of beta-endorphin. It has been suggested that it modulates learning and memory processes in rat. However, the electrophysiological effects that CRF produces on hippocampal neurons have been so far little investigated.

Increase of cerebral phosphocreatine in normal rats after intracerebroventricular administration of creatine.

Intracerebroventricular (ICV) administration of creatine increased cerebral phosphocreatine in normal rats by 67%, the highest increase so far reported in an in vivo model. We used osmotic minipumps (Alzet, Palo Alto, CA, USA) to administer creatine, 0.5 mM, to the lateral ventricle at the rate of 10 microl/h for 3 days.

Antiserum against S-100 protein prevents long term potentiation through a cAMP-related mechanism.

Long term potentiation (LTP) was induced in the CA1 region of rat hippocampal slices by tetanization of the Schaffer collaterals. Local pretreatment of CA1 with serum of rabbits immunized against S-100 prevented the potentiation. However, treatment of the slices with a membrane permeant cAMP analogue, such as 8-Br-cAMP, could protect against the blocking effect of anti S-100 serum.

Involvement of S-100 protein in anoxic long-term potentiation.

In in vitro rat hippocampal slices a short period (2 min) of hypoxia resulted in lasting potentiation of the population spike transynaptically evoked in CA1 by stimulation of Schaffer collaterals ("anoxic LTP"). Pretreatment of slices with antiserum against S-100 protein fully prevented this anoxic LTP. Since also "classical" (i.

An array of Pt-tip microelectrodes for extracellular monitoring of activity of brain slices.

A microelectrode array (MEA) consisting of 34 silicon nitride passivated Pt-tip microelectrodes embedded on a perforated silicon substrate (porosity 35%) has been realized. The electrodes are 47 microns high, of which only the top 15 microns are exposed Pt-tips having a curvature of 0.5 micron.

Exogenous creatine delays anoxic depolarization and protects from hypoxic damage: dose-effect relationship.

Incubation of hippocampal slices with different concentrations of creatine (0.5, 1, 10, 25 mM) results in a dose-dependent increase in intracellular phosphocreatine (PCr). Electrophysiological evidence suggests that this effect can protect neurons from anoxic damage by delaying the depletion of ATP during oxygen deprivation.