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Topic Review
Blood–Brain Barrier Breakdown in Alzheimer’s Disease
The blood–brain barrier (BBB) is a unique and selective feature of the central nervous system’s vasculature. BBB dysfunction has been observed as an early sign of Alzheimer’s Disease (AD) before the onset of dementia or neurodegeneration. The intricate relationship between the BBB and the pathogenesis of AD, especially in the context of neurovascular coupling and the overlap of pathophysiology in neurodegenerative and cerebrovascular diseases, underscores the urgency to understand the BBB’s role more deeply. Preserving or restoring the BBB function emerges as a potentially promising strategy for mitigating the progression and severity of AD. Molecular and genetic changes, such as the isoform ε4 of apolipoprotein E (ApoEε4), a significant genetic risk factor and a promoter of the BBB dysfunction, have been shown to mediate the BBB disruption. Additionally, receptors and transporters like the low-density lipoprotein receptor-related protein 1 (LRP1), P-glycoprotein (P-gp), and the receptor for advanced glycation end products (RAGEs) have been implicated in AD’s pathogenesis.
  • 584
  • 18 Dec 2023
Topic Review
The Significance of Biomarkers in Neurodegenerative Disease Pathology
With the inexorable aging of the global populace, neurodegenerative diseases (NDs) like Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) pose escalating challenges, which are underscored by their socioeconomic repercussions. A pivotal aspect in addressing these challenges lies in the elucidation and application of biomarkers for timely diagnosis, vigilant monitoring, and effective treatment modalities.
  • 583
  • 20 Nov 2023
Topic Review
Ultrasound in Senescent Mice and Alzheimer’s Mouse Models
Ultrasound is routinely used for a wide range of diagnostic imaging applications. However, given that ultrasound can operate over a wide range of parameters that can all be modulated, its applicability extends far beyond the bioimaging field. In fact, the modality has emerged as a hybrid technology that effectively assists drug delivery by transiently opening the blood–brain barrier (BBB) when combined with intravenously injected microbubbles, and facilitates neuromodulation. Studies in aged mice contributed to an insight into how low-intensity ultrasound brings about its neuromodulatory effects, including increased synaptic plasticity and improved cognitive functions, with a potential role for neurogenesis and the modulation of NMDA receptor-mediated neuronal signalling. The currently available ultrasound approaches and how studies in senescent mice are relevant for AD and can accelerate the application of low-intensity ultrasound in the clinic are discussed.
  • 582
  • 22 Jun 2022
Topic Review
Advances in Substance Addiction Research
Addiction is a complex brain disease influenced by genetic, environmental, and neurological factors. Psychostimulants, cocaine, and methamphetamine influence different cell types in different brain regions, with a focus on the neurons responsible for rewarding effects in the nucleus accumbens (NAc) and ventral tegmental area (VTA). Known markers for psychostimulant-induced neuronal plasticity in combination with droplet-based high-throughput single-cell sequencing divided the heterogeneity of cell populations in NAc and VTA into clusters, where all cells of the same type do not respond equally to exposure to psychostimulants. 
  • 580
  • 07 Feb 2024
Topic Review
Language Induced Epilepsy
Language-induced epilepsy is a subcategory of reflex epilepsy during which specific language stimuli appear to be the triggering mechanism. Specifically, higher mental activities, such as reading, speaking, writing, calculating, concentrating, playing chess, reading music, and playing a musical instrument, among others, have been reported as triggering focal or generalized seizures, under certain circumstances. To avoid misconceptions, it is deemed important here to exclude seizures triggered by non-verbal higher brain activities related to spatial processing and ideation or movements from the category of language-induced epilepsy, as such are considered praxis-induced seizures.
  • 578
  • 15 Sep 2023
Topic Review
Sleep among Patients with Chronic Liver Disease
Sleep disturbances are commonly encountered among patients with CLDs and are associated with impaired HRQOL. The present study demonstrated that the more severe the liver disease, the poorer that sleep and QOL are. 
  • 577
  • 09 Jan 2022
Topic Review
Macrophage/Microglia Polarization in Treating Glioblastoma/Multiple Sclerosis
Macrophages and microglia are implicated in several diseases with divergent roles in physiopathology. This discrepancy can be explained by their capacity to endorse different polarization states. Theoretical extremes of these states are called M1 and M2. M1 are pro-inflammatory, microbicidal, and cytotoxic whereas M2 are anti-inflammatory, immunoregulatory cells in favor of tumor progression. In pathological states, these polarizations are dysregulated, thus restoring phenotypes could be an interesting treatment approach against diseases.
  • 577
  • 21 Feb 2022
Topic Review
Dementia Due to Hypoglycemia
Hypoglycemia, a common consequence of diabetes treatment, is associated with severe morbidity and mortality and has become a major barrier to intensifying antidiabetic therapy. Dementia generally refers to the loss of memory, language, problem-solving, and other cognitive functions, which can interfere with daily life, and there are many evidences that diabetes is associated with an increased risk of both vascular and non-vascular dementia. Neuroglycopenia resulting from a hypoglycemic episode in diabetic patients can lead to the degeneration of brain cells, with a resultant cognitive decline, leading to dementia.
  • 577
  • 03 Jul 2023
Topic Review
Machine Learning for Neurodegenerative Diseases Detection
Neurodegenerative diseases (NDs) such as Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) are devastating conditions that can develop without noticeable symptoms, causing irreversible damage to neurons before any signs become clinically evident. NDs are a major cause of disability and mortality worldwide. Web and mobile technologies, through the use of machine learning and AI in apps and web-based tools, offer affordable, accessible screening options for cognitive deficits, showing promise in the early detection of neurodegenerative disorders with demonstrated effectiveness.
  • 575
  • 13 Mar 2024
Topic Review
Synaptic Dysfunction in Alzheimer’s Disease
Disruption in the activity of synapses and the loss of synapses are regarded as early events in the pathogenesis of Alzheimer’s disease that precede the buildup of Aβ deposits in the brain or the clinical expression of the disease. Synaptic loss is evident by the reduction of synaptic proteins in early Alzheimer’s disease and frank atrophy. The extent of synaptic decline in brains at postmortem has been shown to be associated with cognitive function in persons with early Alzheimer’s disease or mild cognitive impairment. The overstimulation of extra-synaptic N-methyl-D-aspartate (NMDA) receptors and the associated synaptic redox stress cause an influx of extracellular calcium, which initiates a series of downstream pathways involving Cdk5/dynamin-related protein 1 (Drp1), caspases, and p-tau. This culminates in mitochondrial dysfunction, apoptosis, and synaptic loss and dysfunction.
  • 571
  • 22 May 2023
Topic Review
Stem Cell Scaffolds for Spinal Cord Injury Treatment
Spinal cord injury (SCI) is a profoundly debilitating yet common central nervous system condition resulting in significant morbidity and mortality rates. Major causes of SCI encompass traumatic incidences such as motor vehicle accidents, falls, and sports injuries. Treatment strategies for SCI aim to improve and enhance neurologic functionality. The ability for neural stem cells (NSCs) to differentiate into diverse neural and glial cell precursors has stimulated the investigation of stem cell scaffolds as potential therapeutics for SCI. Various scaffolding modalities including composite materials, natural polymers, synthetic polymers, and hydrogels have been explored.
  • 570
  • 10 Aug 2023
Topic Review
Toxin Induced Parkinsonism
Patients with Parkinson’s disease admitted to the hospital have unique presentations. This unique subset of patients requires a multidisciplinary approach with a knowledge-based care team that can demonstrate awareness of complications specific to Parkinson’s disease to reduce critical care admissions, morbidity, and mortality. Early recognition of toxic exposures, medication withdrawals, or medication-induced symptoms can reduce morbidity and mortality.
  • 569
  • 11 May 2023
Topic Review Peer Reviewed
Antitumor Strategies Targeting Peptidergic Systems
Peptidergic systems show promise as targets for fighting tumors. While some peptides encourage the growth and spread of tumor cells and angiogenic mechanisms, others display antitumor properties. As such, peptide ligands and receptor antagonists could be used as antitumor agents alone or in conjunction with chemotherapy or radiotherapy. Peptide receptor antagonists can counteract the oncogenic effects of specific peptides by inducing apoptosis in various types of tumor cells, hindering cancer cell migration and inhibiting angiogenesis. Peptides and peptide receptor antagonists are not currently used in clinical practice as antitumor agents. Still, aprepitant, a neurokinin 1 receptor antagonist, is a promising candidate due to its ability to promote apoptosis in many cancer cells. However, to utilize aprepitant as an anticancer agent, the dosage must be increased and administered for a more extended period. Moving beyond current protocols for aprepitant’s use as an antiemetic is essential. Additionally, a common anticancer strategy with aprepitant is possible regardless of cancer cell type. Finally, combining aprepitant with chemotherapy or radiotherapy is encouraged.
  • 569
  • 06 Mar 2024
Topic Review
Chronic Orofacial Pain
In exploring chronic orofacial pain (COFP), it's very important to highlight its global impact on life quality and critiques current diagnostic systems, including the ICD-11, ICOP, and ICHD-3, for their limitations in addressing COFP’s complexity. The mismanagement of pain not only leads to severe physical, psychological, and social repercussions but also incurs substantial economic costs, both in terms of healthcare expenditure and lost productivity.
  • 567
  • 14 Dec 2023
Topic Review
Pathogenesis of Migraine
Migraine, a long-term headache disorder punctuated by episodic bouts, is characterized by repeated instances of severe headaches that present with unique associated symptoms. These include photophobia, a heightened sensitivity to light, and phonophobia, an increased sensitivity to sound. The classification of episodic migraine—an intermittent but recurring form of this disorder—hinges on the frequency with which a patient experiences these debilitating headaches.
  • 566
  • 11 Sep 2023
Topic Review
Common Etiologies of Pediatric Stroke
Pediatric stroke is an important cause of mortality and morbidity in children.  Stroke is a neurologic injury often associated with significant mortality and morbidity. The underlying mechanism is most frequently due to occluded cerebral blood vessels, i.e., ischemic stroke; however, hemorrhagic stroke is an important etiology. 
  • 563
  • 09 Jan 2023
Topic Review
PPARγ in Neuroinflammatory and Demyelinating Events
Increasing evidence suggests that the peroxisome proliferator-activated receptor γ (PPARγ), a member of the nuclear receptor superfamily, plays an important role in physiological processes in the central nervous system (CNS) and is involved in cellular metabolism and repair. Cellular damage caused by acute brain injury and long-term neurodegenerative disorders is associated with alterations of these metabolic processes leading to mitochondrial dysfunction, oxidative stress, and neuroinflammation. Chronic inflammatory damage to the lipid-rich, insulating myelin sheath surrounding axons impairs nerve conduction. Demyelination—the pathological process of myelin sheath loss from axons—can be caused by direct injury to the oligodendrocytes that produce the myelin and provide trophic and metabolic support to axon. PPARγ agonists have demonstrated the potential to be effective treatments for CNS diseases in preclinical models, most drugs have failed to show efficacy in clinical trials of neurodegenerative diseases due likely to the insufficient brain exposure of these PPARγ agonists. Leriglitazone is a novel, blood–brain barrier (BBB)-penetrant PPARγ agonist that is being developed to treat CNS diseases.
  • 563
  • 15 Mar 2023
Topic Review
Endocannabinoid System–Glia Axis
The endocannabinoid system (ECS), comprising endogenous cannabinoids, receptors, and enzymes, has emerged as a critical modulator of sleep patterns, influencing both the initiation and maintenance of sleep. Concurrently and once considered tolerant support cells, glial cells are now recognized as active contributors to neuroinflammatory processes and synaptic regulation. The intricate relationships between the ECS and glia-mediated immune responses in the context of sleep regulation present a novel avenue for understanding the broader implications of disrupted sleep on neural health. The bidirectional communication within the ECS–Glia Axis intersects with sleep regulation, creating a dynamic relationship between neuroinflammation and sleep–wake patterns. Sleep disturbances often coincide with increased neuroinflammation, and chronic activation of the ECS–Glia Axis may contribute to disrupted sleep. Conversely, alterations in sleep architecture influence the activity of the ECS–Glia Axis, suggesting a reciprocal modulation.
  • 558
  • 12 Mar 2024
Topic Review
Co-Occurrence of Substance Use and HIV
Combined antiretroviral therapy (cART) has greatly reduced the severity of HIV-associated neurocognitive disorders in people living with HIV (PLWH); PLWH are more likely than the general population to use drugs and suffer from substance use disorders (SUDs) and to exhibit risky behaviors that promote HIV transmission and other infections. Dopamine-boosting psychostimulants such as cocaine and methamphetamine are some of the most widely used substances among PLWH.
  • 557
  • 01 Nov 2023
Topic Review
Nuclear Factor-like 2 Regulation and Inflammation
The transcription factor Nrf2 (nuclear factor [erythroid-derived 2]-like 2) is of major importance as the defense instrument against OS and alters anti-inflammatory activities related to different pathological states.
  • 555
  • 08 Nov 2023
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