Intraperitoneal injection of lipopolysaccharide prevents seizure-induced respiratory arrest in a DBA/1 mouse model of SUDEP

Objective Sudden unexpected death in epilepsy (SUDEP) is the cause of premature death of 50% patients with chronic refractory epilepsy. Respiratory failure during seizures is regarded as an important mechanism of SUDEP. Previous studies have shown that abnormal serotonergic neurotransmission is involved in the pathogenesis of seizure‐induced respiratory failure, while enhancing serotonergic neurotransmission in the brainstem suppresses it. Because peripheral inflammation is known to enhance serotonergic neuron activation and 5‐HT synthesis and release, we investigated the effect of intraperitoneal lipopolysaccharide (LPS)‐induced inflammation on the S‐IRA susceptibility during audiogenic seizures in DBA/1 mice. Methods After DBA/1 mice were primed by exposing to sound stimulation for three consecutive days, they were tested for seizure severity and seizure‐induced respiratory arrest (S‐IRA) induced by sound stimulation under different conditions. We determined the dose and time course of the effects of intraperitoneal administration of LPS on audiogenic seizures and S‐IRA. The effects of blocking TLR4 or RAGE receptors and blocking 5‐HT receptors on the LPS‐induced effect on S‐IRA were investigated. Statistical significance was evaluated using the Kruskal‐Wallis test. Results Intraperitoneal injection of LPS significantly had dose‐dependent effects in reducing the incidence of S‐IRA as well as seizure severity in DBA/1 mice. The protective effect of LPS on S‐IRA peaked at 8‐12 hours after LPS injection and was related to both reducing seizure severity and enhancing autoresuscitation. Blocking TLR4 or RAGE receptor with TAK‐242 or FPS‐ZM1, respectively, prior to LPS injection attenuated its effects on S‐IRA and seizure severity. Injection of a nonselective 5‐HT receptor antagonist, cyproheptadine, or a 5‐HT3 receptor antagonist, ondansetron, was effective in blocking LPS‐induced effect on S‐IRA. Immunostaining results showed a significant increase in c‐Fos‐positive serotonergic neurons in the dorsal raphe. Significance This is the first study that demonstrates the effect of intraperitoneal LPS injection‐induced inflammation on reducing S‐IRA susceptibility and provides additional evidence supporting the serotonin hypothesis on SUDEP. Our study suggests that inflammation may enhance brainstem 5‐HT neurotransmission to promote autoresuscitation during seizure and prevent SUDEP

Relationship between temporomandibular joint dynamics and mouthguards: feasibility of a test method

A test system was developed establishing the feasibility of collecting biomechanical data as they relate to the use of mouthguards. Previous experimental studies have examined the physical and mechanical properties of mouthguard materials. This information has been used as a guide for establishing material standards and specifications for the fabrication of mouthguards, but it lacks the key biomechanical parameters required for a thorough mouthguard evaluation. The current study was designed to assess whether the impact force, condylar deflection, and strain superior to the temporomandibular joint region could be measured. A drop test was conducted on a cadaveric specimen to simulate loading at the chin point. To measure the force of impact, an accelerometer was attached to an impactor of known mass. High-speed biplanar (1000 frames per second) radiographs were used to determine condylar displacement. Radio-opaque markers were inserted into the bone at predetermined locations. Total displacement of these markers was determined in reference to anatomical landmarks. Strain gauges were attached to the mandible and skull to monitor the effects of the condyle impacting the base of the skull. Based on the data collected, forces were calculated by determining the product of the time-based acceleration and known mass. A measurable change in force between the mouthguards and the control (no mouthguard) was demonstrated. The average condylar displacement was successfully measured and indicated as an increase in total deflection for impacts conducted with mouthguards. Quantifiable strain was measured in the region above the mandibular fossa with and without the insertion of a mouthguard at all impact conditions. However, it was determined that additional gauges would provide critical data. Key biomechanical parameters for chin-point impacts were determined in the current study. The technique demonstrated that both displacement within the mandibular fossa and loading of the condyles occur during the impact event. Although the current study established a technique that can be used to examine the relationship between mouthguards and jaw-joint injuries, the role, if any, mouthguards play in the reduction of injuries cannot be established until a thorough analysis is completed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74031/1/j.1600-9657.2004.00213.x.pd

The burden of premature mortality of epilepsy in high-income countries: A systematic review from the Mortality Task Force of the International League Against Epilepsy

Since previous reviews of epidemiologic studies of premature mortality among people with epilepsy were completed several years ago, a large body of new evidence about this subject has been published. We aim to update prior reviews of mortality in epilepsy and to reevaluate and quantify the risks, potential risk factors, and causes of these deaths. We systematically searched the Medline and Embase databases to identify published reports describing mortality risks in cohorts and populations of people with epilepsy. We reviewed relevant reports and applied criteria to identify those studies likely to accurately quantify these risks in representative populations. From these we extracted and summarized the reported data. All population-based studies reported an increased risk of premature mortality among people with epilepsy compared to general populations. Standard mortality ratios are especially high among people with epilepsy aged <50 years, among those whose epilepsy is categorized as structural/metabolic, those whose seizures do not fully remit under treatment, and those with convulsive seizures. Among deaths directly attributable to epilepsy or seizures, important immediate causes include sudden unexpected death in epilepsy (SUDEP), status epilepticus, unintentional injuries, and suicide. Epilepsy-associated premature mortality imposes a significant public health burden, and many of the specific causes of death are potentially preventable. These require increased attention from healthcare providers, researchers, and public health professionals

International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible

Dexmedetomidine is neuroprotective in an in vitro model for traumatic brain injury

<p>Abstract</p> <p>Background</p> <p>The α₂-adrenoreceptor agonist dexmedetomidine is known to provide neuroprotection under ischemic conditions. In this study we investigated whether dexmedetomidine has a protective effect in an <it>in vitro </it>model for traumatic brain injury.</p> <p>Methods</p> <p>Organotypic hippocampal slice cultures were subjected to a focal mechanical trauma and then exposed to varying concentrations of dexmedetomidine. After 72 h cell injury was assessed using propidium iodide. In addition, the effects of delayed dexmedetomidine application, of hypothermia and canonical signalling pathway inhibitors were examined.</p> <p>Results</p> <p>Dexmedetomidine showed a protective effect on traumatically injured hippocampal cells with a maximum effect at a dosage of 1 μM. This effect was partially reversed by the simultaneous administration of the ERK inhibitor PD98059.</p> <p>Conclusion</p> <p>In this TBI model dexmedetomidine had a significant neuroprotective effect. Our results indicate that activation of ERK might be involved in mediating this effect.</p

Is the Public willing to help the Nigerian Police during the Boko Haram crisis? A look at moderating factors.

This paper sought the opinion of 200 Nigerians on their willingness to cooperate with the Police during the Boko Haram crisis. Public perceptions of Police effectiveness during the crisis, residence location, gender and religious affiliation were used as moderators. Data was analysed using an explanatory factor analysis and structural equation modelling. Results indicated a strong association between perceived effectiveness and willingness to report to the Police with respondents who question the effectiveness of the Police being less likely to be willing to report criminal activity about Boko Haram. Further to this, the impact of religion on willingness to report was at least partially mediated by perceived effectiveness of the Police with the results showing that Christian respondents perceived the Police as less effective. Females and those living in the North were significantly less willing to report criminal activity to the Police The findings are then discussed in relation to the BH crises and directions for future research are given

Treatment of enterohemorrhagic Escherichia coli (EHEC) infection and hemolytic uremic syndrome (HUS)

Verotoxigenic Escherichia coli (VTEC) are a specialized group of E. coli that can cause severe colonic disease and renal failure. Their pathogenicity derives from virulence factors that enable the bacteria to colonize the colon and deliver extremely powerful toxins known as verotoxins (VT) or Shiga toxins (Stx) to the systemic circulation. The recent devastating E. coli O104:H4 epidemic in Europe has shown how helpless medical professionals are in terms of offering effective therapies. By examining the sources and distribution of these bacteria, and how they cause disease, we will be in a better position to prevent and treat the inevitable future cases of sporadic disease and victims of common source outbreaks. Due to the complexity of pathogenesis, it is likely a multitargeted approach is warranted. Developments in terms of these treatments are discussed