Therapy of Parkinson ’s Disease Subtypes
AbstractEarly descriptions of subtypes of Parkinson ’s disease (PD) are dominated by the approach of predetermined groups. Experts defined, from clinical observation, groups based on clinical or demographic features that appeared to divide PD into clinically distinct subsets. Common bases on which to define subtypes have been motor phenotype (tremo r dominant vs akinetic-rigid or postural instability gait disorder types), age, nonmotor dominant symptoms, and genetic forms. Recently, data-driven approaches have been used to define PD subtypes, taking an unbiased statistical approach to the identification of PD subgrou...
Source: Neurotherapeutics - August 4, 2020 Category: Neurology Source Type: research

ASENT2020 Annual Meeting Abstracts
(Source: Neurotherapeutics)
Source: Neurotherapeutics - August 4, 2020 Category: Neurology Source Type: research

Implementation of Mobile Health Technologies in Clinical Trials of Movement Disorders: Underutilized Potential
AbstractMobile health technologies (mHealth) are patient-worn or portable devices aimed at increasing the granularity and relevance of clinical measurements. The implementation of mHealth has the potential to decrease sample size, duration, and cost of clinical trials. We performed a review of theClinicalTrials.gov database using a standardized approach to identify adoption in and usefulness of mHealth in movement disorders interventional clinical trials. Trial phase, geographical area, availability of data captured, constructs of interest, and outcome priority were collected. Eligible trials underwent quality appraisal us...
Source: Neurotherapeutics - July 30, 2020 Category: Neurology Source Type: research

Management of Tardive Syndrome: Medications and Surgical Treatments
AbstractTardive syndrome (TS) is an iatrogenic, often persistent movement disorder caused by drugs that block dopamine receptors. It has a broad phenotype including movement (orobuccolingual stereotypy, dystonia, tics, and others) and nonmotor features (akathisia and pain). TS has garnered increased attention of late because of the Food and Drug Administration approval of the first therapeutic agents developed specifically for this purpose. This paper will begin with a discussion on pathogenesis, clinical features, and epidemiology. However, the main focus will be treatment options currently available for TS including a su...
Source: Neurotherapeutics - July 27, 2020 Category: Neurology Source Type: research

Advances in Therapeutic Approaches for Spontaneous Intracerebral Hemorrhage
AbstractSpontaneous intracerebral hemorrhage (ICH) results in high rates of morbidity and mortality, with intraventricular hemorrhage (IVH) being associated with even worse outcomes. Therapeutic interventions in acute ICH have continued to emerge with focus on arresting hemorrhage expansion, clot volume reduction of both intraventricular and parenchymal hematomas, and targeting perihematomal edema and inflammation. Large randomized controlled trials addressing the effectiveness of rapid blood pressure lowering, hemostatic therapy with platelet transfusion, and other clotting complexes and hematoma volume reduction using mi...
Source: Neurotherapeutics - July 27, 2020 Category: Neurology Source Type: research

Reperfusion plus Selective Intra-arterial Cooling (SI-AC) Improve Recovery in a Nonhuman Primate Model of Stroke
AbstractEarly reperfusion is increasingly prioritized in ischemic stroke care, but outcomes remain suboptimal. Therefore, there is an urgent need to find neuroprotective approaches that can be combined with reperfusion to maximize efficacy. Here, the neuroprotective mechanisms behind therapeutic hypothermia were evaluated in a monkey model of ischemic stroke. Focal ischemia was induced in adult rhesus monkeys by placing autologous clots in the middle cerebral artery. Monkeys were treated with tissue plasminogen activator (t-PA) alone or t-PA plus selective intra-arterial cooling (SI-AC). Serial MRI scans and functional def...
Source: Neurotherapeutics - July 24, 2020 Category: Neurology Source Type: research

Therapeutic Update on Huntington ’s Disease: Symptomatic Treatments and Emerging Disease-Modifying Therapies
AbstractHuntington ’s disease (HD) is a monogenic neurodegenerative disorder that presents with progressive motor, behavior, and cognitive symptoms leading to early disability and mortality. HD is caused by an expanded CAG repeats in exon 1 of the huntingtin (HTT) gene. The corresponding genetic test allows a clinic al, definite diagnosis in life and the identification of a fully penetrant mutation carrier in a premanifest stage. In addition to the development of symptomatic treatments that attempt to address unmet care needs such as apathy, irritability, and cognition, novel therapies that target pathways spec ific ...
Source: Neurotherapeutics - July 23, 2020 Category: Neurology Source Type: research

Central Nervous System Targets: Supraspinal Mechanisms of Analgesia
AbstractWhile the acute sensation of pain is protective, signaling the presence of actual or potential bodily harm, its persistence is unpleasant. When pain becomes chronic, it has limited evolutionarily advantage. Despite the differing nature of acute and chronic pain, a common theme is that sufferers seek pain relief. The possibility to medicate pain types as varied as a toothache or postsurgical pain reflects the diverse range of mechanism(s) by which pain-relieving “analgesic” therapies may reduce, eliminate, or prevent pain. Systemic application of an analgesic able to cross the blood–brain barrier c...
Source: Neurotherapeutics - July 22, 2020 Category: Neurology Source Type: research

Neuromodulation, Specialized Proresolving Mediators, and Resolution of Pain
AbstractThe current crises in opioid abuse and chronic pain call for the development of nonopioid and nonpharmacological therapeutics for pain relief. Neuromodulation-based approaches, such as spinal cord stimulation, dorsal root ganglion simulation, and nerve stimulation including vagus nerve stimulation, have shown efficacy in achieving pain control in preclinical and clinical studies. However, the mechanisms by which neuromodulation alleviates pain are not fully understood. Accumulating evidence suggests that neuromodulation regulates inflammation and neuroinflammation —a localized inflammation in peripheral nerve...
Source: Neurotherapeutics - July 21, 2020 Category: Neurology Source Type: research

IL-6 Receptor Blockade by Tocilizumab Has Anti-absence and Anti-epileptogenic Effects in the WAG/Rij Rat Model of Absence Epilepsy
AbstractIncreased expression of interleukin-6 (IL-6) both in cerebrospinal fluid (CSF) and plasma is closely associated with convulsive epilepsy and symptom severity of depression. By comparison, at present, little is known about the role of this cytokine in childhood (non-convulsive) absence epilepsy. The aim of this work was to investigate the potential effects of acute and chronic treatment with tocilizumab (TCZ, 10 and 30  mg/kg/day), on absence seizures, their development, and related psychiatric comorbidity in WAG/Rij rats. It is known that lipopolysaccharide (LPS)-induced changes in inflammatory processes incre...
Source: Neurotherapeutics - July 17, 2020 Category: Neurology Source Type: research

Inhibition of the BMP Signaling Pathway Ameliorated Established Clinical Symptoms of Experimental Autoimmune Encephalomyelitis
AbstractBone morphogenetic proteins (BMPs) are secreted growth factors that belong to the transforming growth factor beta superfamily. BMPs have been implicated in physiological processes, but they are also involved in many pathological conditions. Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS); however, its etiology remains elusive. Some evidence points to BMPs as important players in the pathogenesis of inflammatory and autoimmune disorders. In the present work, we studied the expression of BMP2, BMP4, BMP5, BMP6, BMP7, BMP type II receptor, and noggin in the immune system durin...
Source: Neurotherapeutics - July 17, 2020 Category: Neurology Source Type: research

Four-Repeat Tauopathies: Current Management and Future Treatments
AbstractFour-repeat tauopathies are a neurodegenerative disease characterized by brain parenchymal accumulation of a specific isoform of the protein tau, which gives rise to a wide breadth of clinical syndromes encompassing diverse symptomatology, with the most common syndromes being progressive supranuclear palsy-Richardson ’s and corticobasal syndrome. Despite the lack of effective disease-modifying therapies, targeted treatment of symptoms can improve quality of life for patients with 4-repeat tauopathies. However, managing these symptoms can be a daunting task, even for those familiar with the diseases, as they s...
Source: Neurotherapeutics - July 16, 2020 Category: Neurology Source Type: research

Proactive Motor Functional Recovery Following Immersive Virtual Reality –Based Limb Mirroring Therapy in Patients with Subacute Stroke
AbstractVirtual reality (VR) is considered to be a promising therapeutic technology for the rehabilitation of upper extremities (UEs) post-stroke. Recently, we designed and then implemented a neuroscientifically grounded VR protocol for the rehabilitation of patients with stroke. The system provides unilateral and bilateral limb mirroring exercises in a fully immersive virtual environment that may stimulate and activate the mirror neuron system in the brain to help patients for their rehabilitation. Twelve patients with subacute stroke underwent the newly implemented VR treatment in addition to conventional rehabilitation ...
Source: Neurotherapeutics - July 15, 2020 Category: Neurology Source Type: research

Neuroprotective Activities of Long-Acting Granulocyte –Macrophage Colony-Stimulating Factor (mPDM608) in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Intoxicated Mice
AbstractLoss of dopaminergic neurons along the nigrostriatal axis, neuroinflammation, and peripheral immune dysfunction are the pathobiological hallmarks of Parkinson ’s disease (PD). Granulocyte–macrophage colony-stimulating factor (GM-CSF) has been successfully tested for PD treatment. GM-CSF is a known immune modulator that induces regulatory T cells (Tregs) and serves as a neuronal protectant in a broad range of neurodegenerative diseases. Due to its shor t half-life, limited biodistribution, and potential adverse effects, alternative long-acting treatment schemes are of immediate need. A long-acting mouse ...
Source: Neurotherapeutics - July 7, 2020 Category: Neurology Source Type: research

Prolonged Use of NMDAR Antagonist Develops Analgesic Tolerance in Neuropathic Pain via Nitric Oxide Reduction-Induced GABAergic Disinhibition
AbstractNeuropathic pain is usually persistent due to maladaptive neuroplasticity-induced central sensitization and, therefore, necessitates long-term treatment.N-methyl-D-aspartate receptor (NMDAR)-mediated hypersensitivity in the spinal dorsal horn represents key mechanisms of central sensitization. Short-term use of NMDAR antagonists produces antinociceptive efficacy in animal pain models and in clinical practice by reducing central sensitization. However, how prolonged use of NMDAR antagonists affects central sensitization remains unknown. Surprisingly, we find that prolonged blockage of NMDARs does not prevent but agg...
Source: Neurotherapeutics - July 6, 2020 Category: Neurology Source Type: research

Intranasal Dexamethasone Reduces Mortality and Brain Damage in a Mouse Experimental Ischemic Stroke Model
In this study, the effectiveness of intranasal, a highly efficient route to reach the central nervous system, and intraperitoneal dexamethasone administration in the treatment of neuroinflammation was evaluated in a 60-min middle cerebral artery occlusion (MCAO) model in C57BL/6 male mice. We performed a side-by-side comparison using intranasalversus intraperitoneal dexamethasone, a timecourse including immediate (0  h) or 4 or 12 h poststroke intranasal administration, as well as 4 intranasal doses of dexamethasone beginning 12 h after the MCAOversus a single dose at 12  h to identify the most effectiv...
Source: Neurotherapeutics - July 6, 2020 Category: Neurology Source Type: research

Interactions Among lncRNAs/circRNAs, miRNAs, and mRNAs in Neuropathic Pain
AbstractNeuropathic pain (NP) is directly caused by an injury or disease of the somatosensory nervous system. It is a serious type of chronic pain that is a burden to the economy and public health. Although recent studies have improved our understanding of NP, its pathogenesis has not been fully elucidated. Noncoding RNAs, including lncRNAs, circRNAs, and miRNAs, are involved in the pathological development of NP through many mechanisms. In addition, extensive evidence suggests that novel regulatory mechanisms among lncRNAs/circRNAs, miRNAs, and mRNAs play a crucial role in the pathophysiological process of NP. In this rev...
Source: Neurotherapeutics - July 6, 2020 Category: Neurology Source Type: research

Cortical Mechanisms of Single-Pulse Transcranial Magnetic Stimulation in Migraine
AbstractSingle-pulse transcranial magnetic stimulation (sTMS) of the occipital cortex is an effective migraine treatment. However, its mechanism of action and cortical effects of sTMS in migraine are yet to be elucidated. Using calcium imaging and GCaMP-expressing mice, sTMS did not depolarise neurons and had no effect on vascular tone. Pre-treatment with sTMS, however, significantly affected some characteristics of the cortical spreading depression (CSD) wave, the correlate of migraine aura. sTMS inhibited spontaneous neuronal firing in the visual cortex in a dose-dependent manner and attenuatedl-glutamate-evoked firing, ...
Source: Neurotherapeutics - July 6, 2020 Category: Neurology Source Type: research

Allopregnanolone Promotes Neuronal and Oligodendrocyte Differentiation In Vitro and In Vivo : Therapeutic Implication for Alzheimer ’s Disease
In this study, we investigated Allo regulation of neuronal differentiation of adult mouse neural stem cells from both sexes. Outcomes indicated that the age-dependent shift from neuronal to glial differentiation was accelerated and magnified in 3xTgAD adult NSCs compared to th at in age-matched non-Tg NSCs. Coincident with the decline in neuronal differentiation, the number of immature neurons declined earlier in 3xTgAD mice, which was consistent with observations in the aged Alzheimer’s human brain. Allo treatment restored the neuron/astrocyte ratio derived from adult 3xTgAD NSCs and increased both NSC proliferation...
Source: Neurotherapeutics - July 6, 2020 Category: Neurology Source Type: research

The Use of the Selective Imidazoline I 1 Receptor Agonist Carbophenyline as a Strategy for Neuropathic Pain Relief: Preclinical Evaluation in a Mouse Model of Oxaliplatin-Induced Neurotoxicity
In conclusion, carbophenyline showed anti-neuropathic properties both after acute and chronic treatment with preventive effect agains t oxaliplatin-induced astrocyte activation in the spinal cord. Therefore, I1-R agonists emerge as a new class of candidates for the management of oxaliplatin-induced neuropathic pain. (Source: Neurotherapeutics)
Source: Neurotherapeutics - June 22, 2020 Category: Neurology Source Type: research

Relapses During High-Dose Biotin Treatment in Progressive Multiple Sclerosis: a Case-Crossover and Propensity Score-Adjusted Prospective Cohort
AbstractHigh-dose biotin (HDB) is a therapy used in non-active progressive multiple sclerosis (PMS). Some reports have suggested that HDB treatment may be associated with an increased risk of relapse. We evaluate the relationship between exposure to HDB for treating PMS and the risk of relapse. We screened for PMS patients prospectively registered in a French regional cohort being part of the OFSEP national registry. In a case-crossover design among patients who received HDB, we first compared number of relapses before and after initiation of HDB. Second, time to the first clinical relapse was compared between patients who...
Source: Neurotherapeutics - June 15, 2020 Category: Neurology Source Type: research

Management of psychiatric disorders in Parkinson ’s disease
AbstractAffective disorders (depression and anxiety), psychosis, impulse control disorders, and apathy are common and sometimes disabling psychiatric conditions in Parkinson disease (PD). Psychiatric aspects of PD are associated with numerous adverse outcomes, yet in spite of this and their high frequency, there remains incomplete understanding of epidemiology, presentation, risk factors, neural substrate, and management strategies. Psychiatric features are typically co- or multimorbid, and there is great intra- and interindividual variability in presentation [1]. The neuropathophysiological changes that occur in PD, as we...
Source: Neurotherapeutics - June 8, 2020 Category: Neurology Source Type: research

The Nerve to Give BACE Inhibitors a Second Chance?
(Source: Neurotherapeutics)
Source: Neurotherapeutics - June 8, 2020 Category: Neurology Source Type: research

The Antidiabetic Metformin as an Adjunct to Antidepressants in Patients with Major Depressive Disorder: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial
AbstractMetformin (MET) has been reported to have antidepressant effects in animal models and in diabetic patients with depression, owing to its anti-inflammatory, antioxidant, and neuroprotective activity. Accordingly, we proposed that MET would show antidepressant effects in patients with major depressive disorder (MDD) without other comorbidities. In this double-blind placebo-controlled study, 80 adult outpatients with MDD (DSM-IV criteria) and a Hamilton Depression Rating Scale (HAM-D) score>18 were randomized to receive fluoxetine 20 mg once daily plus placebo (n = 40) or fluoxetine 20 mg once daily p...
Source: Neurotherapeutics - June 4, 2020 Category: Neurology Source Type: research

Pharmacological Inhibition of Soluble Epoxide Hydrolase as a New Therapy for Alzheimer ’s Disease
This study suggests that inhibition of inflammation in the brain by targeting sEH is a relevant therapeutic strategy for AD. (Source: Neurotherapeutics)
Source: Neurotherapeutics - June 2, 2020 Category: Neurology Source Type: research

Commentary: The Multiple Sclerosis Controversy: Is It Escalation or Induction High Efficacy?
(Source: Neurotherapeutics)
Source: Neurotherapeutics - June 2, 2020 Category: Neurology Source Type: research

Administration of FK506 from Late Stage of Disease Prolongs Survival of Human Prion-Inoculated Mice
In this study, we tested oral administration of FK506 in knock-in mice expressing chimeric human prion protein (KiChM) that were infected with sCJD to determine if this compound is also effective against a clinically relevant human prion, i.e., one that has not been adapted to mice. Treatment with FK506, started either just before or just after disease onset, suppressed typical sCJD pathology (gliosis) and slightly but significantly prolonged the survival of sCJD-inoculated mice. It would be worthwhile to conduct a clinical trial using FK506, which has been safety-approved and is widely used as a mild immunosuppressant. (S...
Source: Neurotherapeutics - June 1, 2020 Category: Neurology Source Type: research

Treating Post-traumatic Stress Disorder with Neuromodulation Therapies: Transcranial Magnetic Stimulation, Transcranial Direct Current Stimulation, and Deep Brain Stimulation
AbstractPost-traumatic stress disorder (PTSD) is a prevalent and debilitating illness. While standard treatment with pharmacotherapy and psychotherapy may be effective, approximately 20 to 30% of patients remain symptomatic. These individuals experience depression, anxiety, and elevated rates of suicide. For treatment-resistant patients, there is a growing interest in the use of neuromodulation therapies, including transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS). We conducted a systematic review on the use of neuromodulation strategies for PTSD and p...
Source: Neurotherapeutics - May 28, 2020 Category: Neurology Source Type: research

Finding Suitable Clinical Endpoints for a Potential Treatment of a Rare Genetic Disease: the Case of ARID1B
In this study, twelve subjects with ARID1B-related ID and twelve age-matched controls were included in this observational case –control study. Subjects performed a battery of non-invasive neurobehavioral and neurophysiological assessments on two study days. Test domains included cognition, executive functioning, and eye tracking. Furthermore, several electrophysiological assessments were performed. Subjects wore a smartwa tch (Withings® Steel HR) for 6 days. Tests were systematically assessed regarding tolerability, variability, repeatability, difference with control group, and correlation with traditional e...
Source: Neurotherapeutics - May 22, 2020 Category: Neurology Source Type: research

Correction to: Mitochondrial Modulation by Dichloroacetate Reduces Toxicity of Aberrant Glial Cells and Gliosis in the SOD1G93A Rat Model of Amyotrophic Lateral Sclerosis
The authors would like to correct the following errors: In Methods section, subsection Respirometry studies: The statement in parentheses “(oligo-inhibited flux–AA-inhibited flux)” should be deleted (Source: Neurotherapeutics)
Source: Neurotherapeutics - May 20, 2020 Category: Neurology Source Type: research

Translational Neurocritical Care Research: Advancing Understanding and Developing Therapeutics
(Source: Neurotherapeutics)
Source: Neurotherapeutics - May 18, 2020 Category: Neurology Source Type: research

Characterization of More Selective Central Nervous System Nrf2-Activating Novel Vinyl Sulfoximine  Compounds Compared to Dimethyl Fumarate
AbstractThe Nrf2 transcription factor is a key regulator of redox reactions and considered the main target for the multiple sclerosis (MS) drug dimethyl fumarate (DMF). However, exploration of additional Nrf2-activating compounds is motivated, since DMF displays significant off-target effects and has a relatively poor penetrance to the central nervous system (CNS). We de novo synthesized eight vinyl sulfone  and sulfoximine compounds (CH-1–CH-8) and evaluated their capacity to activate the transcription factors Nrf2, NFκB, and HIF1 in comparison with DMF using the pTRAF platform. The novel sulfoximine ...
Source: Neurotherapeutics - May 11, 2020 Category: Neurology Source Type: research

Autoimmune Encephalitis: NMDA Receptor Encephalitis as an Example of Translational Neuroscience
AbstractAutoimmune encephalitis (AE) is a group of disorders causing synaptic receptor dysfunction with a broad range of neurological symptoms that has been historically difficult to differentiate clinically. Today, AE represents an excellent example of the rapid determination of the cause of a disease and the ability to identify potential treatments using relatively simple basic science techniques of investigation. Of the number of autoimmune encephalitides identified thus far, one of the best examples of the impact of basic science studies on disease management is NMDA receptor mediated autoimmune encephalitis (NMDAr-AE)...
Source: Neurotherapeutics - May 11, 2020 Category: Neurology Source Type: research

Septic-Associated Encephalopathy: a Comprehensive Review
AbstractSeptic-associated encephalopathy (SAE) is a key manifestation of sepsis, ranging from delirium to coma and occurring in up to 70% of patients admitted to the ICU. SAE is associated with higher ICU and hospital mortality, and also with poorer long-term outcomes, including cognitive and functional outcomes. The pathophysiology of SAE is complex, and it may involve neurotransmitter dysfunction, inflammatory and ischemic lesions to the brain, microglial activation, and blood –brain barrier dysfunction. Delirium (which is included in the SAE spectrum) is mostly diagnosed with validated scales in the ICU population...
Source: Neurotherapeutics - May 6, 2020 Category: Neurology Source Type: research

Targeting Therapeutic Antibodies to the CNS: a Comparative Study of Intrathecal, Intravenous, and Subcutaneous Anti-Nogo A Antibody Treatment after Stroke in Rats
We examined the effects of a neurite growth-enhancing anti-Nogo A antibody therapy following 3 routes of administration—intrathecal (i.t.), intravenous (i.v.), and subcutaneous (s.c.)—after large photothrombotic strokes in adult rats. Intrathecal treatment of full-length IgG an ti-Nogo A antibodies enhanced recovery of the grasping function, but intravenous or subcutaneous administration had no detectable effect in spite of large amounts of antibodies in the peripheral circulation. Thus, in contrast to intravenous and subcutaneous delivery, intrathecal administration is an effective and reliable way to target C...
Source: Neurotherapeutics - May 6, 2020 Category: Neurology Source Type: research

Cerebellar Astrocyte Transduction as Gene Therapy for Megalencephalic Leukoencephalopathy
AbstractMegalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare genetic disorder belonging to the group of vacuolating leukodystrophies. It is characterized by megalencephaly, loss of motor functions, epilepsy, and mild mental decline. In brain biopsies of MLC patients, vacuoles were observed in myelin and in astrocytes surrounding blood vessels. There is no therapy for MLC patients, only supportive treatment. We show here a preclinical gene therapy approach for MLC using theMlc1 knock-out mouse. An adeno-associated virus coding for human MLC1 under the control of the glial fibrillary acidic protein prom...
Source: Neurotherapeutics - May 5, 2020 Category: Neurology Source Type: research

Defining the Mechanism of Subarachnoid Hemorrhage –Induced Pyrexia
AbstractFever can affect the majority of patients with subarachnoid hemorrhage (SAH) and many times no identifiable source is found for the fever whether infectious or sterile, like deep vein thrombosis. We hypothesized that fever in SAH is mediated by a NON-cyclo-oxygenase-dependent mechanism, which we neologized as subarachnoid hemorrhage –induced pyrexia (SAHiP). This hypothesis was investigated using genetically modified mice, pharmacological manipulation, cerebrospinal fluid from SAH patients, and a large cohort of SAH patients. Mice with deletions of neuronal prostaglandin EP3 receptor, global toll-like recepto...
Source: Neurotherapeutics - May 5, 2020 Category: Neurology Source Type: research

ω-3PUFAs Improve Cognitive Impairments Through Ser133 Phosphorylation of CREB Upregulating BDNF/TrkB Signal in Schizophrenia
In conclusion, these findings indicate that MK801-induced SZ lesions dephosphorylate CREB at Ser133 site, leading to neuron damage, and ω-3PUFAs improve SZ cognitive impairments by upregulati ng the CREB/BDNF/TrkB pathway, which provides new clues for the mechanism of SZ cognitive impairments, and a basis for therapeutic intervention. (Source: Neurotherapeutics)
Source: Neurotherapeutics - May 4, 2020 Category: Neurology Source Type: research

Resuscitating the Globally Ischemic Brain: TTM and Beyond
AbstractCardiac arrest (CA) afflicts ~  550,000 people each year in the USA. A small fraction of CA sufferers survive with a majority of these survivors emerging in a comatose state. Many CA survivors suffer devastating global brain injury with some remaining indefinitely in a comatose state. The pathogenesis of global brain injury sec ondary to CA is complex. Mechanisms of CA-induced brain injury include ischemia, hypoxia, cytotoxicity, inflammation, and ultimately, irreversible neuronal damage. Due to this complexity, it is critical for clinicians to have access as early as possible to quantitative metrics for dia...
Source: Neurotherapeutics - May 4, 2020 Category: Neurology Source Type: research

Correction to: Imaging Guidance for Therapeutic Delivery: the Dawn of Neuroenergetics
This article was updated to correct figs. 3, 4 and 5 that were interchanged in the HTML version of the article during the production process. (Source: Neurotherapeutics)
Source: Neurotherapeutics - May 4, 2020 Category: Neurology Source Type: research

Immunotherapies for Aging-Related Neurodegenerative Diseases —Emerging Perspectives and New Targets
AbstractNeurological disorders such as Alzheimer ’s disease (AD), Lewy body dementia (LBD), frontotemporal dementia (FTD), and vascular dementia (VCID) have no disease-modifying treatments to date and now constitute a dementia crisis that affects 5 million in the USA and over 50 million worldwide. The most common pathological hallmark of these a ge-related neurodegenerative diseases is the accumulation of specific proteins, including amyloid beta (Aβ), tau, α-synuclein (α-syn), TAR DNA-binding protein 43 (TDP43), and repeat-associated non-ATG (RAN) peptides, in the intra- and extracellular spaces of ...
Source: Neurotherapeutics - April 28, 2020 Category: Neurology Source Type: research

SIRT2 Inhibition Improves Functional Motor Recovery After Peripheral Nerve Injury
AbstractSirtuin-2 (Sirt2) is a member of the NAD (+)-dependent protein deacetylase family involved in neuroprotection, cellular metabolism, homeostasis, and stress responses after injury of the nervous system. So far, no data have been published describing the role of SIRT2 in motor functional recovery after damage. We found that SIRT2 expression and deacetylase activity were increased within motoneurons after axotomy. To shed light onto the biological relevance of this change, we combinedin vitro andin vivo models with pharmacological and genetic ablation approaches. We found thatSIRT2 KO (knockout) mice exhibited improve...
Source: Neurotherapeutics - April 22, 2020 Category: Neurology Source Type: research

Spreading Depolarizations and Subarachnoid Hemorrhage
AbstractCortical spreading depolarizations (SD) are strongly associated with worse tissue injury and clinical outcomes in the setting of aneurysmal subarachnoid hemorrhage (SAH). Animal studies have suggested a causal relationship, and new therapies to target SDs are starting to be tested in clinical studies. A recent set of single-center randomized trials assessed the effect of the phosphodiesterase inhibitor cilostazol in patients with SAH. Cilostazol led to improved functional outcomes and SD-related metrics in treated patients through a putative mechanism of improved cerebral blood flow. Another promising therapeutic a...
Source: Neurotherapeutics - April 22, 2020 Category: Neurology Source Type: research

Anterior Cingulate Cortex Implants for Alcohol Addiction: A Feasibility Study
This study assessed the effectiveness and feasibility of suppressing alcohol craving using cortical implants of the rdACC using a controlled one-group pre- and post-test study design. Eight intractable alcohol-dependent participants (four males and four females) were implanted with two Lamitrode 44 electrodes over the rdACC bilaterally connected to an internal pulse generator (IPG). The primary endpoint, self-reported alcohol craving reduced by 60.7% (p = 0.004) post- compared to pre-stimulation. Adverse events occurred in four out of the eight participants. Electrophysiology findings showed that among respon...
Source: Neurotherapeutics - April 22, 2020 Category: Neurology Source Type: research

Therapeutic Development of Apolipoprotein E Mimetics for Acute Brain Injury: Augmenting Endogenous Responses to Reduce Secondary Injury
AbstractOver the last few decades, increasing evidence demonstrates that the neuroinflammatory response is a double-edged sword. Although overly robust inflammatory responses may exacerbate secondary tissue injury, inflammatory processes are ultimately necessary for recovery. Traditional drug discovery often relies on reductionist approaches to isolate and modulate specific intracellular pathways believed to be involved in disease pathology. However, endogenous brain proteins are often pleiotropic in order to regulate neuroinflammation and recovery mechanisms. Thus, a process of “backward translation” aims to h...
Source: Neurotherapeutics - April 21, 2020 Category: Neurology Source Type: research

Activation of LXR β Signaling in the Amygdala Confers Anxiolytic Effects Through Rebalancing Excitatory and Inhibitory Neurotransmission upon Acute Stress
In this study, we found stress-induced anxiety led to the expression reduction of LXRβ not LXRα in mice amygdala. GW3965, a dual agonist for both LXRα and LXRβ, alleviated anxiety-like behaviors of stressed mice through activation of LXRβ, confirmed by the knockdown of LXRβ m ediated by lentiviral shRNAs in the basolateral amygdala (BLA). This was paralleled by correcting the disequilibrium of E/I neurotransmission in the stressed BLA. Importantly, GW3965 exerted anxiolytic effects by correcting the promoted amplitude and frequency of miniature excitatory postsynaptic cu rrent (mEPSC), and a...
Source: Neurotherapeutics - April 15, 2020 Category: Neurology Source Type: research

Wake-Promoting and EEG Spectral Effects of Modafinil After Acute or Chronic Administration in the R6/2 Mouse Model of Huntington ’s Disease
AbstractHuntington ’s disease (HD) is characterised by progressive symptoms including cognitive deficits and sleep/wake disturbances reflected in an abnormal electroencephalography (EEG). Modafinil, a wake-promoting and cognitive-enhancing drug, has been considered as a treatment for HD. We used HD (R6/2) mice to in vestigate the potential for using modafinil to treat sleep-wake disturbance in HD. R6/2 mice show sleep-wake and EEG changes similar to those seen in HD patients, with increased rapid eye movement sleep (REMS), decreased wakefulness/increased non-REMS (NREMS), and pathological changes in EEG spectra , par...
Source: Neurotherapeutics - April 15, 2020 Category: Neurology Source Type: research

Imaging Guidance for Therapeutic Delivery: The Dawn of Neuroenergetics
AbstractModern neurocritical care relies on ancillary diagnostic testing in the form of multimodal monitoring to address acute changes in the neurological homeostasis. Much of our armamentarium rests upon physiological and biochemical surrogates of organ or regional level metabolic activity, of which a great deal is invested at the metabolic –hemodynamic–hydrodynamic interface to rectify the traditional intermediaries of glucose consumption. Despite best efforts to detect cellular neuroenergetics, current modalities cannot appreciate the intricate coupling between astrocytes and neurons. Invasive monitoring is ...
Source: Neurotherapeutics - April 2, 2020 Category: Neurology Source Type: research

Pharmacological BACE Inhibition Improves Axonal Regeneration in Nerve Injury and Disease Models
AbstractWhile the peripheral nervous system is able to repair itself following injury and disease, recovery is often slow and incomplete, with no available treatments to enhance the effectiveness of regeneration. Using knock-out and transgenic overexpressor mice, we previously reported that BACE1, an aspartyl protease, as reported by Hemming et al. (PLoS One 4:12,2009), negatively regulates peripheral nerve regeneration. Here, we investigated whether pharmacological inhibition of BACE may enhance peripheral nerve repair following traumatic nerve injury or neurodegenerative disease. BACE inhibitor-treated mice had increased...
Source: Neurotherapeutics - March 31, 2020 Category: Neurology Source Type: research

Long Noncoding RNA POU3F3 and α-Synuclein in Plasma L1CAM Exosomes Combined with β-Glucocerebrosidase Activity: Potential Predictors of Parkinson’s Disease
This study used an ultrasens itive methodology, fluorescence nanoparticle tracking analysis (NTA), to measure plasma L1CAM exosomes and Quanterix Simoa to measure α-syn concentrations in L1CAM exosomes. Eighty-five healthy controls and 93 PD patients were enrolled, and several scales were used to rate the severity of PD. Recei ver operating characteristic (ROC) curves were applied to map the diagnostic accuracy of categorizing PD patients and healthy subjects. We found increased Linc-POU3F3 and α-syn concentrations in L1CAM exosomes and decreased GCase activity in PD patients compared with controls. The three b...
Source: Neurotherapeutics - March 31, 2020 Category: Neurology Source Type: research