Time-restricted feeding (TRF) is known to promote longevity and brain function, and potentially prevent neurological diseases. Animal studies show that TRF enhances brain-derived neurotrophic factor (BDNF) signaling and regulates autophagy and neuroinflammation, supporting synaptic plasticity, neurogenesis and neuroprotection. Feeding/fasting paradigms influence the circadian cycle, with TRF aligning circadian cycle-related gene expression, and thus altering physiological processes.
View Article and Find Full Text PDFBackground: Preconditioning by intermittent fasting is linked to improved cognition and motor function, and enhanced recovery after stroke. Although the duration of fasting was shown to elicit different levels of neuroprotection after ischemic stroke, the impact of time of fasting with respect to the circadian cycles remains unexplored.
Methods: Cohorts of mice were subjected to a daily 16-hour fast, either during the dark phase (active-phase intermittent fasting) or the light phase (inactive-phase intermittent fasting) or were fed ad libitum.
Clinical studies have shown that traumatic brain injury (TBI) increases the onset of Parkinson's disease (PD) in later life by >50%. Oxidative stress, endoplasmic reticulum (ER) stress, and inflammation are the major drivers of both TBI and PD pathologies. We presently evaluated if curtailing oxidative stress and ER stress concomitantly using a combination of apocynin and tert-butylhydroquinone and salubrinal during the acute stage after TBI in mice reduces the severity of late-onset PD-like pathology.
View Article and Find Full Text PDFRobust keys exist for the family-level groups of Cynipoidea. However, for most regions of the world, keys to genera are not available. To address this gap as it applies to North America, a fully illustrated key is provided to facilitate identification of the tribes and genera of rose gall, herb gall, and inquiline gall wasps known from the region.
View Article and Find Full Text PDFHeterogeneity and variability of symptoms due to the type, site, age, sex, and severity of injury make each case of traumatic brain injury (TBI) unique. Considering this, a universal treatment strategy may not be fruitful in managing outcomes after TBI. Most of the pharmacological therapies for TBI aim at modifying a particular pathway or molecular process in the sequelae of secondary injury rather than a holistic approach.
View Article and Find Full Text PDFThe microRNA-21 (miR-21) levels in the brain are crucial in determining post-stroke brain damage and recovery. The miR-21 exerts neuroprotection by targeting mRNAs that translate proteins that mediate brain damage. We currently determined the efficacy and efficiency of intravenously administered miR-21 mimic after focal cerebral ischemia in mice.
View Article and Find Full Text PDFJ Cereb Blood Flow Metab
February 2024
We previously showed that knockdown or deletion of Fos downstream transcript (FosDT; a stroke-induced brain-specific long noncoding RNA) is neuroprotective. We presently tested the therapeutic potential of FosDT siRNA in rodents subjected to transient middle cerebral artery occlusion (MCAO) using the Stroke Treatment Academic Industry Roundtable criteria, including sex, age, species, and comorbidity. FosDT siRNA (IV) given at 30 min of reperfusion significantly improved motor function recovery (rotarod test, beam walk test, and adhesive removal test) and reduced infarct size in adult and aged spontaneously hypertensive rats of both sexes.
View Article and Find Full Text PDFEpigenetic and epitranscriptomic modifications that regulate physiological processes of an organism at the DNA and RNA levels, respectively, are novel therapeutic candidates for various neurological diseases. Gut microbiota and its metabolites are known to modulate DNA methylation and histone modifications (epigenetics), as well as RNA methylation especially N6-methyladenosine (epitranscriptomics). As gut microbiota as well as these modifications are highly dynamic across the lifespan of an organism, they are implicated in the pathogenesis of stroke and depression.
View Article and Find Full Text PDFThe identities of most arthropod associates of cynipid-induced oak galls in the western Palearctic are generally known. However, a comprehensive accounting of associates has been performed for only a small number of the galls induced by the estimated 700 species of cynipid gall wasps in the Nearctic. This gap in knowledge stymies many potential studies of diversity, coevolution, and community ecology, for which oak gall systems are otherwise ideal models.
View Article and Find Full Text PDFBackground: FTO (fat mass and obesity-associated protein) demethylates -methyladenosine (mA), which is a critical epitranscriptomic regulator of neuronal function. We previously reported that ischemic stroke induces mA hypermethylation with a simultaneous decrease in FTO expression in neurons. Currently, we evaluated the functional significance of restoring FTO with an adeno-associated virus 9, and thus reducing mA methylation in poststroke brain damage.
View Article and Find Full Text PDFThe complex pathophysiology of post-traumatic brain damage might need a polypharmacological strategy with a combination of drugs that target multiple, synergistic mechanisms. We currently tested a combination of apocynin (curtails formation of reactive oxygen species), tert-butylhydroquinone (promotes disposal of reactive oxygen species), and salubrinal (prevents endoplasmic reticulum stress) following a moderate traumatic brain injury (TBI) induced by controlled cortical impact in adult mice. Adult mice of both sexes treated with the above tri-combo showed alleviated motor and cognitive deficits, attenuated secondary lesion volume, and decreased oxidative DNA damage.
View Article and Find Full Text PDFOxidative stress plays a crucial role in traumatic brain injury (TBI) pathogenesis. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) formed in excess after TBI synergistically contribute to secondary brain damage together with lipid peroxidation products (reactive aldehydes) and inflammatory mediators. Furthermore, oxidative stress, endoplasmic reticulum stress and inflammation potentiate each other.
View Article and Find Full Text PDFTraumatic brain injury (TBI) is known to promote significant DNA damage irrespective of age, sex, and species. Chemical as well as structural DNA modification start within minutes and persist for days after TBI. Although several DNA repair pathways are induced following TBI, the simultaneous downregulation of some of the genes and proteins of these pathways leads to an aberrant overall DNA repair process.
View Article and Find Full Text PDFEvery year stroke claims more than 6 million lives worldwide. The majority of them are ischemic stroke. Small molecule-based therapeutics for ischemic stroke has attracted a lot of attention, but none has been shown to be clinically useful so far.
View Article and Find Full Text PDFThe constant failure of single-target drug therapies for ischemic stroke necessitates the development of novel pleiotropic pharmacological treatment approaches, to effectively combat the aftermath of this devastating disorder. The major objective of our study involves a multi-target drug repurposing strategy to stabilize hypoxia-inducible factor-1 α (HIF-1α) via a structure-based screening approach to simultaneously inhibit its regulatory proteins, PHD2, FIH, and pVHL. Out of 1424 Food and Drug Administration (FDA)-approved drugs that were screened, folic acid (FA) emerged as the top hit and its binding potential to PHD2, FIH, and pVHL was further verified by re-docking, molecular dynamics (MD) simulation and by Drug Affinity Responsive Target Stability (DARTS) assay.
View Article and Find Full Text PDFCarnosine is a naturally occurring pleotropic dipeptide which influences multiple deleterious mechanisms that are activated during stroke. Numerous published studies have reported that carnosine has robust efficacy in ischemic stroke models. To further evaluate these data, we have conducted a systematic review and meta-analysis of published studies.
View Article and Find Full Text PDFNecroptosis or programmed necrosis is evident in various neurological disorders such as ischemic stroke. Receptor interacting serine/threonine protein kinase 3 (RIPK3) is one of the crucial targets of necroptosis and inhibition of this protein exerts neuroprotection. However, knowledge regarding the three-dimensional structure and binding site information of this protein is lacking.
View Article and Find Full Text PDF