The fraction of activated N-methyl-d-Aspartate receptors during synaptic transmission remains constant in the presence of the glutamate release inhibitor riluzole

Excessive N-methyl-d-aspartate (NMDA) receptor activation is widely accepted to mediate calcium-dependent glutamate excitotoxicity. The uncompetitive, voltage-dependent NMDA receptor antagonist memantine has been successfully used clinically in the treatment of neurodegenerative dementia and is internationally registered for the treatment of moderate to severe Alzheimer′s disease. Glutamate release inhibitors (GRIs) may also be promising for the therapy of some neurodegenerative diseases. During the clinical use of GRIs, it could be questioned whether there would still be a sufficient number of active NMDA receptors to allow any additional effects of memantine or similar NMDA receptor antagonists. To address this question, we determined the fraction of NMDA receptors contributing to postsynaptic events in the presence of therapeutically relevant concentrations of the GRI riluzole (1 μM) using an in vitro hippocampal slice preparation. We measured the charge transfer of pharmacologically isolated excitatory synaptic responses before and after the application of the selective, competitive NMDA receptor antagonist D-AP5 (100 μM). The fraction of activated NMDA receptors under control conditions did not differ from those in the presence of riluzole. It is therefore likely that NMDA receptor antagonists would be able to exert additional therapeutic effects in combination therapy with GRIs

Syndromics: A Bioinformatics Approach for Neurotrauma Research

Substantial scientific progress has been made in the past 50 years in delineating many of the biological mechanisms involved in the primary and secondary injuries following trauma to the spinal cord and brain. These advances have highlighted numerous potential therapeutic approaches that may help restore function after injury. Despite these advances, bench-to-bedside translation has remained elusive. Translational testing of novel therapies requires standardized measures of function for comparison across different laboratories, paradigms, and species. Although numerous functional assessments have been developed in animal models, it remains unclear how to best integrate this information to describe the complete translational “syndrome” produced by neurotrauma. The present paper describes a multivariate statistical framework for integrating diverse neurotrauma data and reviews the few papers to date that have taken an information-intensive approach for basic neurotrauma research. We argue that these papers can be described as the seminal works of a new field that we call “syndromics”, which aim to apply informatics tools to disease models to characterize the full set of mechanistic inter-relationships from multi-scale data. In the future, centralized databases of raw neurotrauma data will enable better syndromic approaches and aid future translational research, leading to more efficient testing regimens and more clinically relevant findings

Does dexmedetomidine reduce secondary damage after spinal cord injury? An experimental study

The aim of this experimental study was to investigate the possible protective effect of dexmedetomidine (DEX) on traumatic spinal cord injury (SCI). Twenty-two New Zealand rabbits were divided into three groups: sham (no drug or operation, n = 6), Control [SCI + single dose of 1 mL saline intraperitoneally (i.p), after trauma; n = 8] and DEX (SCI + 1 μg/kg dexmedetomidine in 1 mL, i.p, after trauma, n = 8). Laminectomy was performed at T10 and balloon angioplasty catheter was applied extradurally. Four and 24 h after surgery, rabbits were evaluated by an independent observer according to the Tarlov scoring system. Blood, cerebrospinal fluid (CSF), tissue samples from spinal cord were taken for biochemical and histopathological evaluations. After 4 h of SCI, all animals in control or DEX treated groups became paraparesic. On the other hand, 24 h after SCI, partial improvements were observed in both control and DEX treated groups. Traumatic SCI leads to increase in the lipid peroxidation and decreases enzymatic or nonenzymatic endogenous antioxidative defense systems. Again, SCI leads to apoptosis in spinal cord. DEX treatment slightly prevented lipid peroxidation and augmented endogenous antioxidative defense systems in CSF or spinal cord tissue, but failed to prevent apoptosis or neurodeficit after traumatic SCI. Therefore, it could be suggested that treatment with dexmedetomidine does not produce beneficial results in SCI

Dantrolene can reduce secondary damage after spinal cord injury

The aim of this experimental study was to investigate the possible protective effects of dantrolene on traumatic spinal cord injury (SCI). Twenty-four New Zealand rabbits were divided into three groups: Sham (no drug or operation, n = 8), Control (SCI + 1 mL saline intraperitoneally (i.p.), n = 8), and DNT (SCI + 10 mg/kg dantrolene in 1 mL, i.p., n = 8). Laminectomy was performed at T10 and balloon catheter was applied extradurally. Four and 24 h after surgery, rabbits were evaluated according to the Tarlov scoring system. Blood, cerebrospinal fluid and tissue sample from spinal cord were taken for measurements of antioxidant status or detection of apoptosis. After 4 h SCI, all animals in control or DNT-treated groups became paraparesic. Significant improvement was observed in DNT-treated group, 24 h after SCI, with respect to control. Traumatic SCI led to an increase in the lipid peroxidation and a decrease in enzymic or non-enzymic endogenous antioxidative defense systems, and increase in apoptotic cell numbers. DNT treatment prevented lipid peroxidation and augmented endogenous enzymic or non-enzymic antioxidative defense systems. Again, DNT treatment significantly decreased the apoptotic cell number induced by SCI. In conclusion, experimental results observed in this study suggest that treatment with dantrolene possess potential benefits for traumatic SCI