Alexandra Gramowski

University of Rostock · Lehrstuhl für Tierphysiologie

Introduction: Phenotypic screening has led to the majority of successfully launched CNS drugs in the last 15 years. In vitro models using primary cultures are widely used for testing drug candidates. Here, the use of human induced pluripotent stem cell-derived (hiPSC) neurons is presented as an in vitro drug discovery assay of increased predictabil...

The present study was performed in an attempt to develop an in vitro integrated testing strategy (ITS) to evaluate drug-induced neurotoxicity. A number of endpoints were analyzed using two complementary brain cell culture models and an in vitro blood-brain barrier (BBB) model after single and repeated exposure treatments with selected drugs that co...

Recently, an analysis revealed the phenotypic approaches to be the more successful strategy for small-molecule and therefore are reconsidered and reintroduced as a complementary strategy of a target-based approach for drug discovery (Swinney and Anthony, Nat Rev Drug Discov. 2011). Phenotypic screening with neuronal cell cultures on microelectrode...

Persistent pain states, such as those caused by nerve injury or inflammation, are associated with altered sensations, allodynia and hyperalgesia, that are resistant to traditional analgesics. A contribution to development and maintenance in altered pain perception comes from nociceptive processing and descending modulation from supraspinal sites. A...

Novel dermorphin tetrapeptides are described in which Tyr(1) is replaced by Dmt(1), where d-Ala(2) and Gly(4) are N-methylated, and where Phe(3)-Gly(4) residue is substituted by the constrained Aba(3)-Gly(4) peptidomimetic. Most of these peptidic ligands displayed binding affinities in the nanomolar range for both μ- and δ-opioid receptors but no d...

Neuronal assemblies within the nervous system produce electrical activity that can be recorded in terms of action potential patterns. Such patterns provide a sensitive endpoint to detect effects of a variety of chemical and physical perturbations. They are a function of synaptic changes and do not necessarily involve structural alterations. In vitr...

Because of its diverse physical and chemical properties, lanthanum has been used in various industrial and medical fields. However, until recently, its effects at the cellular and molecular level had hardly been investigated. Using primary cortical networks grown on microelectrode array neurochips, we investigated the acute functional neurotoxicity...

Microelectrode arrays (MEAs) have been in use over the past decade and a half to study multiple aspects of electrically excitable cells. In particular, MEAs have been applied to explore the pharmacological and toxicological effects of numerous compounds on spontaneous activity of neuronal and cardiac cell networks. The MEA system enables simultaneo...

Nanomaterials are extensively used in industry and daily life, but little is known about possible health effects. An intensified research regarding toxicity of nanomaterials is urgently needed. Several studies have demonstrated that nanoparticles (NPs; diameter < 100 nm) can be transported to the central nervous system; however, interference of NPs...

Functional screening of CNS drugs with neuronal network cultures on microelectrode arrays can elucidate different modes of action for a given substance at different concentrations. This concentration-dependent profiling of CNS drug candidates is a new feature of this technology. KeywordsFunctional screening–neuronal network cultures–microelectrode...

Amyloid beta (Aβ) peptide deposits are one of the hallmarks of Alzheimer's disease (AD). For a long time it was believed that amyloid deposits in the senile plaques in the brain of patients with AD play a central role in the etiology of AD. Later many reports ascribed this role to different aggregates of Aβ (from fibrils, through high oligomers to...

Amyloid beta (Aβ) peptides have been suggested to play an essential role in the generation of Alzheimer's disease (AD). In spite of the abundance of findings the exact correlation of Aβ and AD remains unclear. Aβ could influence cognition by impairment of basic neurotransmission mechanisms without causing directly neuronal death. This view is suppo...

We optimized the novel technique of multielectrode neurochip recordings for the rapid and efficient screening of neuroactivity. Changes in the spontaneous activity of cultured networks of primary cortical neurons were quantified to evaluate the action of drugs on the firing dynamics of complex network activity. The multiparametric assessment of ele...

The innovative alternative method of multielectrode neurochip recording, which offers improvements compared to standard animal experimentation, has been further optimised by advanced multi-parametric data analysis and used to study toxicity patterns of known toxicants. Neuronal networks on 64-electrode neurochips develop long-term stable spontaneou...

The latest advances in research on intracranial implantation of hardware models of neural circuitry. The continuing development of implantable neural prostheses signals a new era in bioengineering and neuroscience research. This collection of essays outlines current advances in research on the intracranial implantation of devices that can communica...

This paper presents a novel and comprehensive method to identify substances on the basis of electrical activity and is a substantial improvement for drug screening. The spontaneous activity of primary neuronal networks is influenced by neurotransmitters, ligands, and other substances in a similar fashion as known from in vivo pharmacology. However,...

The Molecular Adsorbent Recirculating System (MARS) is a nonbiological liver support method based on the principles of dialysis, filtration, and adsorption. It allows the safe and efficient removal of both albumin-bound and water-soluble toxic metabolites, including ammonia, aromatic amino acids, tryptophan, and related phenolic and indolic product...

Hepatic encephalopathy (HE) results from impaired detoxification capacity of the liver leading to accumulation of various substances that may impair the function of the central nervous system (CNS).1—5

Cultured spinal cord networks grown on microelectrode arrays display complex patterns of spontaneous burst and spike activity. During disinhibition with bicuculline and strychnine, synchronized burst patterns routinely emerge. However, the variability of both intra- and interculture burst periods and durations are typically large under these condit...

We have utilized cultured neuronal networks grown on microelectrode arrays to demonstrate rapid, reliable detection of a toxic compound, trimethylolpropane phosphate (TMPP). Initial experiments, which were performed blind, demonstrated rapid classification of the compound as a convulsant, a finding consistent with previous whole animal neurobehavio...

We used spontaneously active monolayer networks in vitro, cultured on thin film microelectrode arrays as experimental platforms for the determination of trimethyltin chloride (TMT) toxicity. Two different tissues of the mouse CNS (spinal cord and auditory cortex) exhibited characteristic and dose-dependent changes of their electrophysiological acti...