Degenerative and vascular lesions of the brain have synergistic effects in dementia of the elderly

Parkinson’s disease (PD) affects around ten million people worldwide and is considered the second most prevalent neurodegenerative disease after Alzheimer’s disease. In addition, there is a higher risk incidence in the elderly population. The main PD hallmarks include the loss of dopaminergic neurons and the development of Lewy bodies. Unfortunately, motor symptoms only start to appear when around 50–70% of dopaminergic neurons have already been lost. This particularly poses a huge challenge for early diagnosis and therapeutic effectiveness. Actually, pharmaceutical therapy is able to relief motor symptoms, but as the disease progresses motor complications and severe side-effects start to appear. In this review, we explore the research conducted so far in order to repurpose drugs for PD with the use of nanodelivery systems, alternative administration routes, and nanotheranostics. Overall, studies have demonstrated great potential for these nanosystems to target the brain, improve drug pharmacokinetic profile, and decrease side-effects.

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From Exercise to Cognitive Performance: Role of Irisin

Applied Sciences ◽

10.3390/app11157120 ◽

2021 ◽

Vol 11 (15) ◽

pp. 7120

Author(s):

Mirko Pesce ◽

Irene La Fratta ◽

Teresa Paolucci ◽

Alfredo Grilli ◽

Antonia Patruno ◽

...

Keyword(s):

The Elderly ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Beneficial Effects ◽

General Exercise ◽

Fibronectin Type Iii ◽

Exercise Induced ◽

Fibronectin Type Iii Domain ◽

The Brain

The beneficial effects of exercise on the brain are well known. In general, exercise offers an effective way to improve cognitive function in all ages, particularly in the elderly, who are considered the most vulnerable to neurodegenerative disorders. In this regard, myokines, hormones secreted by muscle in response to exercise, have recently gained attention as beneficial mediators. Irisin is a novel exercise-induced myokine, that modulates several bodily processes, such as glucose homeostasis, and reduces systemic inflammation. Irisin is cleaved from fibronectin type III domain containing 5 (FNDC5), a transmembrane precursor protein expressed in muscle under the control of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). The FNDC5/irisin system is also expressed in the hippocampus, where it stimulates the expression of the neurotrophin brain-derived neurotrophic factor in this area that is associated with learning and memory. In this review, we aimed to discuss the role of irisin as a key mediator of the beneficial effects of exercise on synaptic plasticity and memory in the elderly, suggesting its roles within the main promoters of the beneficial effects of exercise on the brain.

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Epilepsy and Related Disorders

10.2310/neuro.1244 ◽

2018 ◽

Author(s):

Barbara Dworetzky ◽

Jong Woo Lee

Keyword(s):

Differential Diagnosis ◽

Generic Drugs ◽

Sudden Change ◽

Epileptic Seizures ◽

Quality Measures ◽

The Elderly ◽

Childhood And Adolescence ◽

Nonepileptic Seizures ◽

Infancy And Early Childhood ◽

The Brain

Epilepsy is a chronic disorder of the brain characterized by recurrent unprovoked seizures. A seizure is a sudden change in behavior that is accompanied by electrical discharges in the brain. Many patients presenting with a first-ever seizure are surprised to find that it is a very common event. A reversible or avoidable seizure precipitant, such as alcohol, argues against underlying epilepsy and therefore against treatment with medication. This chapter discusses the epidemiology, etiology, and classification of epilepsy and provides detailed descriptions of neonatal syndromes, syndromes of infancy and early childhood, and syndromes of late childhood and adolescence. The pathophysiology, diagnosis, and differential diagnosis are described, as are syncope, migraine, and psychogenic nonepileptic seizures. Two case histories are provided, as are sections on treatment (polytherapy, brand-name versus generic drugs, surgery, stimulation therapy, dietary treatments), complications of epilepsy and related disorders, prognosis, and quality measures. Special topics discussed are women?s issues and the elderly. Figures illustrate a left midtemporal epileptic discharge, wave activity during drowsiness, cortical dysplasias, convulsive syncope, rhythmic theta activity, right hippocamal sclerosis, and right temporal hypometabolism. Tables describe international classifications of epileptic seizures and of epilepsies, epilepsy syndromes and related seizure disorders, differential diagnosis of seizure, differentiating epileptic versus nonepileptic seizures, antiepileptic drugs, status epilepticus protocol for treatment, when to consider referral to a specialist, and quality measures in epilepsy. This review contains 7 figures, 10 tables, and 33 references. Key Words: Seizures, focal (partial)seizure, generalized seizures, Myoclonic seizures, Atonic seizures, Concurrent electromyographyTonic-clonic (grand mal) seizures

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Natural product-based nanomedicine: Recent advances and issues for the treatment of Alzheimer's disease

Current Neuropharmacology ◽

10.2174/1570159x20666211217163540 ◽

2021 ◽

Vol 20 ◽

Author(s):

Choy Ker Woon ◽

Wong Kah Hui ◽

Razif Abas ◽

Muhammad Huzaimi Haron ◽

Srijit Das ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Natural Products ◽

Medicinal Plants ◽

Drug Transport ◽

The Elderly ◽

Current Evidence ◽

Alternative Approach ◽

Progressive Neurodegeneration ◽

The Brain

: Alzheimer's disease (AD) affects the elderly and is characterized by progressive neurodegeneration caused by different pathologies. The most significant challenges in treating AD include the inability of medications to reach the brain because of its poor solubility, low bioavailability, and the presence of the blood-brain barrier (BBB). Additionally, current evidence suggests the disruption of BBB plays an important role in the pathogenesis of AD. One of the critical challenges in treating AD is the ineffective treatments and its severe adverse effects. Nanotechnology offers an alternative approach to facilitate the treatment of AD by overcoming the challenges in drug transport across the BBB. Various nanoparticles (NP) loaded with natural products were reported to aid in drug delivery for the treatment of AD. The nano- sized entities of NP are great platforms for incorporating active materials from natural products into formulations that can be delivered effectively to the intended action site without compromising the material’s bioactivity. The review highlights the applications of medicinal plants, their derived components, and various nanomedicine-based approaches for the treatment of AD. The combination of medicinal plants and nanotechnology may lead to new theragnostic solutions for the treatment of AD in the future.

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Immunosenescence of Natural Killer Cells, Inflammation, and Alzheimer’s Disease

International Journal of Alzheimer s Disease ◽

10.1155/2018/3128758 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 8

Author(s):

Corona Solana ◽

Raquel Tarazona ◽

Rafael Solana

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Nk Cells ◽

Natural Killer ◽

Nk Cell ◽

Neurodegenerative Disorder ◽

The Elderly ◽

Lymphoid Cells ◽

Target Cells ◽

The Brain

Alzheimer’s disease (AD) represents the most common cause of dementia in the elderly. AD is a neurodegenerative disorder characterized by progressive memory loss and cognitive decline. Although the aetiology of AD is not clear, both environmental factors and heritable predisposition may contribute to disease occurrence. In addition, inflammation and immune system alterations have been linked to AD. The prevailing hypothesis as cause of AD is the deposition in the brain of amyloid beta peptides (Aβ). Although Aβ have a role in defending the brain against infections, their accumulation promotes an inflammatory response mediated by microglia and astrocytes. The production of proinflammatory cytokines and other inflammatory mediators such as prostaglandins and complement factors favours the recruitment of peripheral immune cells further promoting neuroinflammation. Age-related inflammation and chronic infection with herpes virus such as cytomegalovirus may also contribute to inflammation in AD patients. Natural killer (NK) cells are innate lymphoid cells involved in host defence against viral infections and tumours. Once activated NK cells secrete cytokines such as IFN-γ and TNF-α and chemokines and exert cytotoxic activity against target cells. In the elderly, changes in NK cell compartment have been described which may contribute to the lower capacity of elderly individuals to respond to pathogens and tumours. Recently, the role of NK cells in the immunopathogenesis of AD is discussed. Although in AD patients the frequency of NK cells is not affected, a high NK cell response to cytokines has been described together with NK cell dysregulation of signalling pathways which is in part involved in this altered behaviour.

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Exosomal delivery of therapeutic modulators through the blood–brain barrier; promise and pitfalls

Cell & Bioscience ◽

10.1186/s13578-021-00650-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Morteza Heidarzadeh ◽

Yasemin Gürsoy-Özdemir ◽

Mehmet Kaya ◽

Aysan Eslami Abriz ◽

Amir Zarebkohan ◽

...

Keyword(s):

Molecular Mechanisms ◽

Large Population ◽

Drug Carriers ◽

The Elderly ◽

Brain Parenchyma ◽

Main Question ◽

Inflammatory Conditions ◽

Degenerative Disorders ◽

Delivery Strategies ◽

The Brain

AbstractNowadays, a large population around the world, especially the elderly, suffers from neurological inflammatory and degenerative disorders/diseases. Current drug delivery strategies are facing different challenges because of the presence of the BBB, which limits the transport of various substances and cells to brain parenchyma. Additionally, the low rate of successful cell transplantation to the brain injury sites leads to efforts to find alternative therapies. Stem cell byproducts such as exosomes are touted as natural nano-drug carriers with 50–100 nm in diameter. These nano-sized particles could harbor and transfer a plethora of therapeutic agents and biological cargos to the brain. These nanoparticles would offer a solution to maintain paracrine cell-to-cell communications under healthy and inflammatory conditions. The main question is that the existence of the intact BBB could limit exosomal trafficking. Does BBB possess some molecular mechanisms that facilitate the exosomal delivery compared to the circulating cell? Although preliminary studies have shown that exosomes could cross the BBB, the exact molecular mechanism(s) beyond this phenomenon remains unclear. In this review, we tried to compile some facts about exosome delivery through the BBB and propose some mechanisms that regulate exosomal cross in pathological and physiological conditions.

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Effectiveness of home-based cognitive training program on a cognitive level, the activity of daily living among elderly persons with mild cognitive impairment in selected community settings of Puducherry

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i4.3149 ◽

2020 ◽

Vol 11 (4) ◽

pp. 5301-5309

Author(s):

Govindakumari R ◽

Vijayalakshmi ◽

Sai Sailesh Kumar Goothy ◽

Vijay Raghvan

Keyword(s):

Training Program ◽

Cognitive Training ◽

Structural Changes ◽

The Elderly ◽

Elderly Persons ◽

Community Settings ◽

Daily Life Activities ◽

Home Based ◽

Study Results ◽

The Brain

Aging is a physiological process that leads to both biological and psychological changes. The brain undergoes structural changes as a part of aging. According to the investigator's best knowledge and based on the extensive review, no structured study was conducted in India to test the effectiveness of cognitive training program. Hence, the present study was conducted to test the effectiveness of a home-based training program on select outcomes. A total of 314 elderly participants were recruited for the study after obtaining the written informed consent. After recruiting, the participants were randomly grouped into two groups, that is control and intervention groups, with 157 participants in each group. The intervention was administered to the experimental group. The present study results suggest that the home-based cognitive training program is effective in improving cognitive functions and daily life activities. The study recommends further detailed and multi-centered studies in this area to recommend the implementation of the program in the management of the cognitive impairments of the elderly.

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Partial cortico-hippocampectomy in cats, as therapy for refractory temporal epilepsy: A descriptive cadaveric study

PLoS ONE ◽

10.1371/journal.pone.0244892 ◽

2021 ◽

Vol 16 (1) ◽

pp. e0244892

Author(s):

Jessica Zilli ◽

Monika Kressin ◽

Anne Schänzer ◽

Marian Kampschulte ◽

Martin J. Schmidt

Keyword(s):

Temporal Lobe ◽

Tissue Injury ◽

Histopathological Examination ◽

Hippocampal Sclerosis ◽

Intraoperative Complications ◽

Temporal Cortex ◽

Cadaveric Study ◽

Vascular Lesions ◽

Temporal Epilepsy ◽

The Brain

Cats, similar to humans, are known to be affected by hippocampal sclerosis (HS), potentially causing antiepileptic drug (AED) resistance. HS can occur as a consequence of chronic seizure activity, trauma, inflammation, or even as a primary disease. In humans, temporal lobe resection is the standardized therapy in patients with refractory temporal lobe epilepsy (TLE). The majority of TLE patients are seizure free after surgery. Therefore, the purpose of this prospective cadaveric study is to establish a surgical technique for hippocampal resection in cats as a treatment for AED resistant seizures. Ten cats of different head morphology were examined. Pre-surgical magnetic resonance imaging (MRI) and computed tomography (CT) studies of the animals’ head were carried out to complete 3D reconstruction of the head, brain, and hippocampus. The resected hippocampal specimens and the brains were histologically examined for tissue injury adjacent to the hippocampus. The feasibility of the procedure, as well as the usability of the removed specimen for histopathological examination, was assessed. Moreover, a micro-CT (mCT) examination of the brain of two additional cats was performed in order to assess temporal vasculature as a reason for possible intraoperative complications. In all cats but one, the resection of the temporal cortex and the hippocampus were successful without any evidence of traumatic or vascular lesions in the surrounding neurovascular structures. In one cat, the presence of mechanical damage (a fissure) of the thalamic surface was evident in the histopathologic examination of the brain post-resection. All hippocampal fields and the dentate gyrus were identified in the majority of the cats via histological examination. The study describes a new surgical approach (partial temporal cortico-hippocampectomy) offering a potential treatment for cats with clinical and diagnostic evidence of temporal epilepsy which do not respond adequately to the medical therapy.

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Efficacy and immunogenicity of MultiTEP-based DNA vaccines targeting human α-synuclein: prelude for IND enabling studies

npj Vaccines ◽

10.1038/s41541-021-00424-2 ◽

2022 ◽

Vol 7 (1) ◽

Author(s):

Changyoun Kim ◽

Armine Hovakimyan ◽

Karen Zagorski ◽

Tatevik Antonyan ◽

Irina Petrushina ◽

...

Keyword(s):

Dna Vaccines ◽

Neurodegenerative Disorder ◽

Neuronal Damage ◽

Lewy Bodies ◽

Amyloid Β ◽

The Elderly ◽

Brain Regions ◽

Dependent Manner ◽

Lewy Neurites ◽

The Brain

AbstractAccumulation of misfolded proteins such as amyloid-β (Aβ), tau, and α-synuclein (α-Syn) in the brain leads to synaptic dysfunction, neuronal damage, and the onset of relevant neurodegenerative disorder/s. Dementia with Lewy bodies (DLB) and Parkinson’s disease (PD) are characterized by the aberrant accumulation of α-Syn intracytoplasmic Lewy body inclusions and dystrophic Lewy neurites resulting in neurodegeneration associated with inflammation. Cell to cell propagation of α-Syn aggregates is implicated in the progression of PD/DLB, and high concentrations of anti-α-Syn antibodies could inhibit/reduce the spreading of this pathological molecule in the brain. To ensure sufficient therapeutic concentrations of anti-α-Syn antibodies in the periphery and CNS, we developed four α-Syn DNA vaccines based on the universal MultiTEP platform technology designed especially for the elderly with immunosenescence. Here, we are reporting on the efficacy and immunogenicity of these vaccines targeting three B-cell epitopes of hα-Syn aa85–99 (PV-1947D), aa109–126 (PV-1948D), aa126–140 (PV-1949D) separately or simultaneously (PV-1950D) in a mouse model of synucleinopathies mimicking PD/DLB. All vaccines induced high titers of antibodies specific to hα-Syn that significantly reduced PD/DLB-like pathology in hα-Syn D line mice. The most significant reduction of the total and protein kinase resistant hα-Syn, as well as neurodegeneration, were observed in various brain regions of mice vaccinated with PV-1949D and PV-1950D in a sex-dependent manner. Based on these preclinical data, we selected the PV-1950D vaccine for future IND enabling preclinical studies and clinical development.

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