High-Resolution Respirometry for Mitochondrial Function in Rodent Brain.

High-resolution mitochondrial respirometry is a modern technique that enables to measure mitochondrial respiration in various cell types. It contains chambers with oxygen sensors that measure oxygen concentration via polarography and calculate its consumption. The chamber contains plastic stoppers with injection ports that allow the injection of samples and different substrates, inhibitors, and uncoupler substances to measure mitochondrial respiration with high efficiency. These substances act on the mitochondrial electron transport chain (ETC) and help to assess the mitochondrial ATP production capacity and oxidative phosphorylation. The respirograph obtained with the help of software represents the oxygen consumption in each stage after adding different reagents.

Hypoxia and its effect on the cellular system.

Eukaryotic cells utilize oxygen for different functions of cell organelles owing to cellular survival. A balanced oxygen homeostasis is an essential requirement to maintain the regulation of normal cellular systems. Any changes in the oxygen level are stressful and can alter the expression of different homeostasis regulatory genes and proteins. Lack of oxygen or hypoxia results in oxidative stress and formation of hypoxia inducible factors (HIF) and reactive oxygen species (ROS). Substantial cellular damages due to hypoxia have been reported to play a major role in various pathological conditions. There are different studies which demonstrated that the functions of cellular system are disrupted by hypoxia. Currently, study on cellular effects following hypoxia is an important field of research as it not only helps to decipher different signaling pathway modulation, but also helps to explore novel therapeutic strategies. On the basis of the beneficial effect of hypoxia preconditioning of cellular organelles, many therapeutic investigations are ongoing as a promising disease management strategy in near future. Hence, the present review discusses about the effects of hypoxia on different cellular organelles, mechanisms and their involvement in the progression of different diseases.

Inosine attenuates post-stroke neuroinflammation by modulating inflammasome mediated microglial activation and polarization.

To date, various agents and molecules have been developed to treat post-stroke neuroinflammation; however, none of them are clinically successful. Post-stroke neuroinflammation is primarily attributed to microglial polarization as the generation of inflammasome complexes shifts microglia to their M1 phenotype and regulates the downstream cascade. Inosine, an adenosine derivative reported to maintain cellular energy homeostasis in stressed conditions. Although the exact mechanism is still unexplored, various studies have reported that it can stimulate axonal sprouting in different neurodegenerative diseases. Hence, our present study aims to decipher the molecular mechanism of inosine mediated neuroprotection by modulating inflammasome signaling towards altered microglial polarization in ischemic stroke. Inosine was administered intraperitoneally to male Sprague Dawley rats at 1 h post-ischemic stroke and was further evaluated for neurodeficit score, motor coordination and long-term neuroprotection. Brains were harvested for infarct size estimation, biochemical assays and molecular studies. Inosine administration at 1 h post ischemic stroke decreased infarct size, neurodeficit score, and improved motor co-ordination. Normalization of biochemical parameters were achieved in the treatment groups. Microglial polarization towards its anti-inflammatory phenotype and modulation of inflammation were evident by relevant gene and protein expression studies. The outcome provides preliminary evidence of inosine mediated alleviation of post-stroke neuroinflammation via modulation of microglial polarization towards its anti-inflammatory form through regulating the inflammasome activation.

Cardiolipin-Mediated Alleviation of Mitochondrial Dysfunction Is a Neuroprotective Effect of Statin in Animal Model of Ischemic Stroke.

In clinical settings, the benefit of statin for stroke is debatable as regular statin users may suffer from myalgia, statin-associated myopathy (SAM), and rarely rhabdomyolysis. Studies suggest that patients on statin therapy show lesser vulnerability toward ischemic stroke and post-stroke frailty. Both pre- and post-treatment benefits of statin have been reported as evident by its neuroprotective effects in both cases. As mitochondrial dysfunction following stroke is the fulcrum for neuronal death, we hereby explore the role of statin in alleviating mitochondrial dysfunction by regulating the mitochondrial dynamics. In the present study, we intend to evaluate the role of statin in modulating cardiolipin-mediated mitochondrial functionality and further providing a therapeutic rationale for repurposing statins either as preventive or an adjunctive therapy for stroke.

Pharmacological Strategies for Stroke Intervention: Assessment of Pathophysiological Relevance and Clinical Trials.

OBJECTIVES: The present review describes stroke pathophysiology in brief and discusses the spectrum of available treatments with different promising interventions that are in clinical settings or are in clinical trials. METHODS: Relevant articles were searched using Google Scholar, Cochrane Library, and PubMed. Keywords for the search included ischemic stroke, mechanisms, stroke interventions, clinical trials, and stem cell therapy. RESULTS AND CONCLUSION: Stroke accounts to a high burden of mortality and morbidity around the globe. Time is an important factor in treating stroke. Treatment options are limited; however, agents with considerable efficacy and tolerability are being continuously explored. With the advances in stroke interventions, new therapies are being formulated with a hope that these may aid the ongoing protective and reparative processes. Such therapies may have an extended therapeutic time window in hours, days, weeks, or longer and may have the advantage to be accessible by a majority of the patients.