Small RNA signatures of acute ischemic stroke in L1CAM positive extracellular vesicles.

L1CAM-positive extracellular vesicles (L1EV) are an emerging biomarker that may better reflect ongoing neuronal damage than other blood-based biomarkers. The physiological roles and regulation of L1EVs and their small RNA cargoes following stroke is unknown. We sought to characterize L1EV small RNAs following stroke and assess L1EV RNA signatures for diagnosing stroke using weighted gene co-expression network analysis and random forest (RF) machine learning algorithms.

ATF3 is a neuron-specific biomarker for spinal cord injury and ischaemic stroke.

Background: Although many molecules have been investigated as biomarkers for spinal cord injury (SCI) or ischemic stroke, none of them are specifically induced in central nervous system (CNS) neurons following injuries with low baseline expression. However, neuronal injury constitutes a major pathology associated with SCI or stroke and strongly correlates with neurological outcomes. Biomarkers characterized by low baseline expression and specific induction in neurons post-injury are likely to better correlate with injury severity and recovery, demonstrating higher sensitivity and specificity for CNS injuries compared to non-neuronal markers or pan-neuronal markers with constitutive expressions.

Suppressing APOE4-induced mortality and cellular damage by targeting VHL.

Mortality rate increases with age and can accelerate upon extrinsic or intrinsic damage to individuals. Identifying factors and mechanisms that curb population mortality rate has wide-ranging implications. Here, we show that targeting the VHL-1 (Von Hippel-Lindau) protein suppresses mortality caused by distinct factors, including elevated reactive oxygen species, temperature, and , the genetic variant that confers high risks of neurodegeneration in Alzheimer's diseases and all-cause mortality in humans.

Management of Status Epilepticus and Indications for Inpatient Electroencephalography Monitoring.

Status epilepticus (SE) is a neurologic emergency requiring immediate time-sensitive treatment to minimize neuronal injury and systemic complications. Minimizing time to administration of first- and second-line therapy is necessary to optimize the chances of successful seizure termination in generalized convulsive SE (GCSE). The approach to refractory and superrefractory GCSE is less well defined.

Diabetes, stroke, and neuroresilience: looking beyond hyperglycemia.

Ischemic stroke is a leading cause of morbidity and mortality among type 2 diabetic patients. Preclinical and translational studies have identified critical pathophysiological mediators of stroke risk, recurrence, and poor outcome in diabetic patients, including endothelial dysfunction and inflammation. Most clinical trials of diabetes and stroke have focused on treating hyperglycemia alone.

Cytoprotection by a naturally occurring variant of ATP5G1 in Arctic ground squirrel neural progenitor cells.

Many organisms in nature have evolved mechanisms to tolerate severe hypoxia or ischemia, including the hibernation-capable Arctic ground squirrel (AGS). Although hypoxic or ischemia tolerance in AGS involves physiological adaptations, little is known about the critical cellular mechanisms underlying intrinsic AGS cell resilience to metabolic stress. Through cell survival-based cDNA expression screens in neural progenitor cells, we identify a genetic variant of AGS that confers cell resilience to metabolic stress.

Resilience to Injury: A New Approach to Neuroprotection?

Despite thousands of neuroprotectants demonstrating promise in preclinical trials, a neuroprotective therapeutic has yet to be approved for the treatment of acute brain injuries such as stroke or traumatic brain injury. Developing a more detailed understanding of models and populations demonstrating "neurological resilience" in spite of brain injury can give us important insights into new translational therapies. Resilience is the process of active adaptation to a stressor.

Neuronal GDPGP1 and glycogen metabolism: friend or foe?

The adult brain consumes glucose for energy needs and stores glucose as glycogen mainly in astrocytes. Schulz et al. (2020.

Diagnosing Balamuthia mandrillaris Encephalitis With Metagenomic Deep Sequencing.

Objective: Identification of a particular cause of meningoencephalitis can be challenging owing to the myriad bacteria, viruses, fungi, and parasites that can produce overlapping clinical phenotypes, frequently delaying diagnosis and therapy. Metagenomic deep sequencing (MDS) approaches to infectious disease diagnostics are known for their ability to identify unusual or novel viruses and thus are well suited for investigating possible etiologies of meningoencephalitis.

Methods: We present the case of a 74-year-old woman with endophthalmitis followed by meningoencephalitis.

Sarcoid polyneuropathy masquerading as chronic inflammatory demyelinating polyneuropathy.

Introduction: Sarcoid polyneuropathy is a rare and clinically heterogeneous disorder that may be the initial presentation of sarcoidosis.

Methods: We report the clinical, electrophysiological, and pathological findings of a patient who carried a diagnosis of sensory-predominant chronic inflammatory demyelinating polyneuropathy (CIDP) for over a decade but was ultimately found to have sarcoid polyneuropathy.

Results: A 36-year-old man presented with a several-week history of gait difficulty and muscle cramps.

Effect of rituximab in patients with leucine-rich, glioma-inactivated 1 antibody-associated encephalopathy.

Importance: This observational study describes the efficacy and safety of rituximab in 5 patients with voltage-gated potassium channel (VGKC)-complex/leucine-rich, glioma-inactivated 1 (LGI1) antibody-associated encephalopathy. Rituximab is a monoclonal antibody that targets CD20 and is used to treat other neurologic and nonneurologic diseases.

Observations: This case series reports sequential seizure frequencies, modified Rankin Scale scores, and VGKC-complex antibody titers in 5 adult patients (median age, 65 years; range, 48-73 years) treated with rituximab.

A practical approach to neurologic evaluation in the intensive care unit.

Delirium and neurologic impairment are extremely common in the intensive care setting, and their delayed identification is an important contributor to patient morbidity. Even in comatose patients, the clinical neurologic examination remains the most accurate and effective tool in assessing nervous system function. Rapid identification of neurologic deficits with a practical and easily reproducible neurologic examination is a core skill for effectively caring for critically ill patients.

Unconscious processing of color and form in metacontrast masking.

Three experiments employed a metacontrast masking procedure to examine the extent and nature of priming effects from visual stimuli not consciously perceived. The results showed effects of unconscious stimuli on subsequent target responses that (1) were more consistent, reliable, and not subject to strategic control, as compared with consciously perceived stimuli (Experiment 1); (2) produced both facilitation and interference of subsequent processing (Experiment 2); and (3) did not influence indirect response-related levels of processing (Experiment 3). These results demonstrate that color and form attributes of unconscious stimuli are sufficiently registered within the visual system to influence behavior, and that some of these unconscious effects occur at early levels of stimulus encoding, prior to higher level perceptual and response-related processes.

Inhibition of ADRP prevents diet-induced insulin resistance.

Diets with high fat content induce steatosis, insulin resistance, and type 2 diabetes. The lipid droplet protein adipose differentiation-related protein (ADRP) mediates hepatic steatosis, but whether this affects insulin action in the liver or peripheral organs in diet-induced obesity is uncertain. We fed C57BL/6J mice a high-fat diet and simultaneously treated them with an antisense oligonucleotide (ASO) against ADRP for 4 wk.

Loss of resistin ameliorates hyperlipidemia and hepatic steatosis in leptin-deficient mice.

Resistin has been linked to components of the metabolic syndrome, including obesity, insulin resistance, and hyperlipidemia. We hypothesized that resistin deficiency would reverse hyperlipidemia in genetic obesity. C57Bl/6J mice lacking resistin [resistin knockout (RKO)] had similar body weight and fat as wild-type mice when fed standard rodent chow or a high-fat diet.

Central resistin induces hepatic insulin resistance via neuropeptide Y.

Sensing of peripheral hormones and nutrients by the hypothalamus plays an important role in maintaining peripheral glucose homeostasis. The hormone resistin impairs the response to insulin in liver and other peripheral tissues. Here we demonstrate that in normal mice resistin delivered in the lateral cerebral ventricle increased endogenous glucose production during hyperinsulinemic-euglycemic clamp, consistent with induction of hepatic insulin resistance.

Brain adipocytokine action and metabolic regulation.

Adipose tissue secretes factors that control various physiological systems. The fall in leptin during fasting mediates hyperphagia and suppresses thermogenesis, thyroid and reproductive hormones, and immune system. On the other hand, rising leptin levels in the fed state stimulate fatty acid oxidation, decrease appetite, and limit weight gain.

Loss of resistin improves glucose homeostasis in leptin deficiency.

Resistin levels are increased in obesity, and hyperresistinemia impairs glucose homeostasis in rodents. Here, we have determined the role of resistin in ob/ob mice that are obese and insulin resistant because of genetic deficiency of leptin. Loss of resistin increased obesity in ob/ob mice by further lowering the metabolic rate without affecting food intake.

Adipokines that link obesity and diabetes to the hypothalamus.

Adipose tissue plays a crucial role in energy homeostasis not only in storing triglyceride, but also responding to nutrient, neural, and hormonal signals, and producing factors which control feeding, thermogenesis, immune and neuroendocrine function, and glucose and lipid metabolism. Adipose tissue secretes leptin, steroid hormones, adiponectin, inflammatory cytokines, resistin, complement factors, and vasoactive peptides. The endocrine function of adipose tissue is typified by leptin.

Unconscious color priming occurs at stimulus- not percept-dependent levels of processing.

Although past studies have shown that visual information can be processed without awareness, the types and levels of this processing have yet to be determined. We used metacontrast masking to explore unconscious priming effects of white, blue, and green stimuli generated on a color video display. We found that a white prime tends to act more like a green than a blue one.

Feedback contributions to visual awareness in human occipital cortex.

It has traditionally been assumed that processing within the visual system proceeds in a bottom-up, feedforward manner from retina to higher cortical areas. In addition to feedforward processing, it is now clear that there are also important contributions to sensory encoding that rely upon top-down, feedback (reentrant) projections from higher visual areas to lower ones. By utilizing transcranial magnetic stimulation (TMS) in a metacontrast masking paradigm, we addressed whether feedback processes in early visual cortex play a role in visual awareness.