Automated analyses for single-fiber electrophysiological recordings using a newly developed Microsoft Excel application and graphical user interface.

BACKGROUND: Electrophysiological recordings of isolated sensory afferents are commonly used in the field of pain research to investigate peripheral mechanisms of nociception in various pain models. The method involves skillful and tedious recordings of teased fibers from nerve preparations as well as time-consuming post-recording analyses. To increase efficiency and productivity of data analyses of recorded action potentials, we developed and validated a novel, easy-to-use Microsoft Excel-based application using Visual Basic Programming. NEW METHOD: A code for the novel program, shigraspike1.0, was written to create a module to include customizable subroutines for analyses for electrical and mechanical responses. Using previously recorded action potentials with tongue-lingual nerve preparations, the program was validated for appropriate execution, ease-of-use, accuracy of the output data and time taken for analyses. RESULTS: We observed appropriate execution of shigraspike1.0 on Windows and iOS desktop platforms that included computation of response latency of the spike of interest using electrical stimulus as well as estimation of the number of impulses at each force with a step-and-hold mechanical ramp of 10-200mN. Output data obtained by shigrapsike1.0 for both stimulus types were accurate and statistically insignificant from manual analyses. COMPARISON WITH EXISTING METHOD: The novel application shigraspike1.0, allows for rapid analyses for single-fiber recordings and takes less than half the time to analyze electrical and mechanical responses compared to manual analyses. CONCLUSIONS: The newly developed shigraspike1.0 application can be a very productive tool to be routinely used for efficient analyses of single-fiber electrophysiology in pain research.

Mitochondrion-specific antioxidants as drug treatments for Alzheimer disease.

Age-related dementias such as Alzheimer disease (AD) have been linked to vascular disorders like hypertension, diabetes and atherosclerosis. These risk factors cause ischemia, inflammation, oxidative damage and consequently reperfusion, which is largely due to reactive oxygen species (ROS) that are believed to induce mitochondrial damage. At higher concentrations, ROS can cause cell injury and death which occurs during the aging process, where oxidative stress is incremented due to an accelerated generation of ROS and a gradual decline in cellular antioxidant defense mechanisms. Neuronal mitochondria are especially vulnerable to oxidative stress due to their role in energy supply and use, causing a cascade of debilitating factors such as the production of giant and/or vulnerable young mitochondrion who's DNA has been compromised. Therefore, mitochondria specific antioxidants such as acetyl-L-carnitine and R-alphalipoic acid seem to be potential treatments for AD. They target the factors that damage mitochondria and reverse its effect, thus eliminating the imbalance seen in energy production and amyloid beta oxidation and making these antioxidants very powerful alternate strategies for the treatment of AD.

Oxidative Stress Induced Mitochondrial Failure and Vascular Hypoperfusion as a Key Initiator for the Development of Alzheimer Disease.

Mitochondrial dysfunction may be a principal underlying event in aging, including age-associated brain degeneration. Mitochondria provide energy for basic metabolic processes. Their decay with age impairs cellular metabolism and leads to a decline of cellular function. Alzheimer disease (AD) and cerebrovascular accidents (CVAs) are two leading causes of age-related dementia. Increasing evidence strongly supports the theory that oxidative stress, largely due to reactive oxygen species (ROS), induces mitochondrial damage, which arises from chronic hypoperfusion and is primarily responsible for the pathogenesis that underlies both disease processes. Mitochondrial membrane potential, respiratory control ratios and cellular oxygen consumption decline with age and correlate with increased oxidant production. The sustained hypoperfusion and oxidative stress in brain tissues can stimulate the expression of nitric oxide synthases (NOSs) and brain endothelium probably increase the accumulation of oxidative stress products, which therefore contributes to blood brain barrier (BBB) breakdown and brain parenchymal cell damage. Determining the mechanisms behind these imbalances may provide crucial information in the development of new, more effective therapies for stroke and AD patients in the near future.