scholarly journals MSC Secretome as a Promising Tool for Neuroprotection and Neuroregeneration in a Model of Intracerebral Hemorrhage

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2031
Author(s):  
Maxim Karagyaur ◽  
Stalik Dzhauari ◽  
Nataliya Basalova ◽  
Natalia Aleksandrushkina ◽  
Georgy Sagaradze ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Neurological Outcome ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Lesion Volume ◽  
Therapeutic Approaches ◽  
Beneficial Effects ◽  
Tissue Repair And Regeneration ◽  
Promising Tool ◽  
Neurologic Disorders ◽  
The Brain

Multipotent mesenchymal stromal cells (MSCs) are considered to be critical contributors to injured tissue repair and regeneration, and MSC-based therapeutic approaches have been applied to many peripheral and central neurologic disorders. It has been demonstrated that the beneficial effects of MSC are mainly mediated by the components of their secretome. In the current study, we have explored the neuroprotective potential of the MSC secretome in a rat model of intracerebral hemorrhage and shown that a 10-fold concentrated secretome of human MSC and its combination with the brain-derived neurotrophic factor (BDNF) provided a better survival and neurological outcome of rats within 14 days of intracerebral hemorrhage compared to the negative (non-treated) and positive (BDNF) control groups. We found that it was due to the ability of MSC secretome to stimulate neuron survival under conditions of glutamate-induced neurotoxicity. However, the lesion volume did not shrink in these rats, and this also correlated with prominent microglia activation. We hypothesize that this could be caused by the species-specificity of the used MSC secretome and provide evidence to confirm this. Thus, we have found that allogenic rat MSC secretome was more effective than xenogenic human MSC secretome in the rat intracerebral hemorrhage model: it reduced the volume of the lesion and promoted excellent survival and neurological outcome of the treated rats.

scholarly journals Role of Acupuncture in the Management of Severe Acquired Brain Injuries (sABIs)

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Loredana Cavalli ◽  
Lucia Briscese ◽  
Tiziana Cavalli ◽  
Paolo Andre ◽  
Maria Chiara Carboncini
Keyword(s):  
Brain Injuries ◽  
Neuronal Regeneration ◽  
Asian Countries ◽  
Rehabilitative Treatment ◽  
Beneficial Effects ◽  
Nervous System Activity ◽  
Neurologic Disorders ◽  
Central Nervous System Activity ◽  
The Brain

Acupuncture therapy has been used to treat several disorders in Asian countries and its use is increasing in Western countries as well. Current literature assessed the safety and efficacy of acupuncture in the acute management and rehabilitation of patients with neurologic disorders. In this paper, the role of acupuncture in the treatment of acute severe acquired brain injuries is described, acting on neuroinflammation, intracranial oedema, oxidative stress, and neuronal regeneration. Moreover, beneficial effects of acupuncture on subacute phase and chronic outcomes have been reported in controlling the imbalance of IGF-1 hormone and in decreasing spasticity, pain, and the incidence of neurovegetative crisis. Moreover, acupuncture may have a positive action on the arousal recovery. Further work is needed to understand the effects of specific acupoints on the brain. Allegedly concurrent neurophysiological measurements (e.g., EEG) may help in studying acupuncture-related changes in central nervous system activity and determining its potential as an add-on rehabilitative treatment for patients with consciousness disorders.

scholarly journals Butin attenuates brain edema in a rat model of intracerebral hemorrhage by anti inflammatory pathway

2018 ◽  
Vol 9 (1) ◽  
pp. 7-12 ◽  
Author(s):  
Peiyu Li ◽  
Cheng Jiwu
Keyword(s):  
Intracerebral Hemorrhage ◽  
Brain Edema ◽  
Treated Group ◽  
Control Group ◽  
Lesion Volume ◽  
Dependent Manner ◽  
Neurological Score ◽  
Factor Α ◽  
The Brain ◽  
Brain Tissues

Abstract Background This study evaluates the effect of butin against brain edema in intracerebral hemorrhage (ICH). Methodology ICH was induced by injecting bacterial collagenase in the brain and all the animals were separated into four groups such as control group, ICH group treated with vehicle, Butin 25 and 50 mg/kg group receives butin (25 and 50 mg/kg, i.p.)60 min after the induction of ICH in all animals. One day after neurological score, hemorrhagic injury and expressions of protein responsible for apoptosis and inflammatory cytokines were assessed in the brain tissue of ICH rats. Result Neurological scoring significantly increased and hemorrhagic lesion volume decreased in butin treated group of rats compared to ICH group. However, treatment with butin significantly decreases the ratio of Bax/Bcl-2 and protein expression of Cleaved caspase-3 than ICH group in dose dependent manner. Level of inflammatory mediators such as tumor necrosis factor-α (TNF-α) and interlukin-6 (IL-6) in the brain tissues were significantly decreased in the butin treated group than ICH group. In addition butin attenuates the altered signaling pathway of NF-κB in the brain tissues of ICH rats. Conclusion Our study concludes that butin attenuates the altered behavior and neuronal condition in ICH rats by reducing apoptosis and inflammatory response.

Abstract TP111: Haptoglobin Improves Intracerebral Hemorrhage Outcomes by Modulating Angiogenic Responses

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Jenna Leclerc ◽  
Tina Esfandiary ◽  
Sylvain Dore
Keyword(s):  
Intracerebral Hemorrhage ◽  
Tissue Repair ◽  
Autologous Blood ◽  
Healing Process ◽  
Acute Injury ◽  
Neurological Deficits ◽  
Lesion Volume ◽  
Oxidative Potential ◽  
Ambulatory Ability ◽  
The Brain

Intracerebral hemorrhage (ICH) most often occurs spontaneously and is one of the most devastating stroke subtypes. Following ICH, toxic blood components must be cleared from the brain as part of the tissue repair/scar formation healing process. Angiogenesis is a key physiologic mechanism that facilitates tissue repair following acute injury, but must be tightly regulated to prevent excessive activity and deleterious consequences. After ICH, regulation of angiogenesis within the appropriate range in injured brain regions would allow for delivery of glucose and oxygen to support the energy-requiring reparative processes and facilitate the necessary entry of peripheral cells involved. Haptoglobin (Hp) is an acute phase protein that binds extracorpuscular hemoglobin, thereby directly reducing its oxidative potential, and Hp has also been shown to have potent angiogenic, vasculogenic, and wound healing properties. Using the autologous blood model of ICH, we have shown that Hp overexpression significantly improves ICH outcomes and reduces oxidative processes. Here, we aimed to confirm our previous results and further characterize the mechanisms by which Hp exerts these neuroprotective effects. Hp was overexpressed in the brain using adeno-associated viral vectors and ICH was induced using the collagenase-induced spontaneous bleeding model, which is accompanied by clinically relevant intraventricular hemorrhage. In line with our previous study, Hp-overexpressing mice demonstrate significantly smaller lesion volumes (p<0.01) and less residual blood (p<0.05). This reduced ICH-induced brain injury is accompanied by trends towards improved ambulatory ability and less focal neurological deficits at 72h post-ICH (p<0.07). Hp-overexpressing mice have significantly reduced PECAM-1 expression and tend to have less VEGF immunoreactivity. After correcting for lesion volume, Hp-overexpressing mice retain the decreased PECAM-1 expression, but VEGF expression is increased, collectively suggesting a direct role of Hp in positively modulating angiogenesis after ICH. Hp therapy could represent a new treatment strategy for ICH through a multifactorial mechanism that includes the modulation of important angiogenic processes.

scholarly journals Multipotent mesenchymal stromal cell–derived exosomes improve functional recovery after experimental intracerebral hemorrhage in the rat

2019 ◽  
Vol 131 (1) ◽  
pp. 290-300 ◽  
Author(s):  
Yuxia Han ◽  
Don Seyfried ◽  
Yuling Meng ◽  
Dongmei Yang ◽  
Lonni Schultz ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Functional Recovery ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Functional Improvement ◽  
Control Group ◽  
Lesion Volume ◽  
Novel Therapy ◽  
Multipotent Mesenchymal Stromal Cell ◽  
Male Wistar Rats ◽  
Social Odor

OBJECTIVEPrevious studies have demonstrated that transplanted multipotent mesenchymal stromal cells (MSCs) improve functional recovery in rats after experimental intracerebral hemorrhage (ICH). In this study the authors tested the hypothesis that administration of multipotent MSC-derived exosomes promotes functional recovery, neurovascular remodeling, and neurogenesis in a rat model of ICH.METHODSSixteen adult male Wistar rats were subjected to ICH via blood injection into the striatum, followed 24 hours later by tail vein injection of 100 μg protein of MSC-derived exosomes (treatment group, 8 rats) or an equal volume of vehicle (control group, 8 rats); an additional 8 rats that had identical surgery without blood infusion were used as a sham group. The modified Morris water maze (mMWM), modified Neurological Severity Score (mNSS), and social odor–based novelty recognition tests were performed to evaluate cognitive and sensorimotor functional recovery after ICH. All 24 animals were killed 28 days after ICH or sham procedure. Histopathological and immunohistochemical analyses were performed for measurements of lesion volume and neurovascular and white matter remodeling.RESULTSCompared with the saline-treated controls, exosome-treated ICH rats showed significant improvement in the neurological function of spatial learning and motor recovery measured at 26–28 days by mMWM and starting at day 14 by mNSS (p < 0.05). Senorimotor functional improvement was measured by a social odor–based novelty recognition test (p < 0.05). Exosome treatment significantly increased newly generated endothelial cells in the hemorrhagic boundary zone, neuroblasts and mature neurons in the subventricular zone, and myelin in the striatum without altering the lesion volume.CONCLUSIONSMSC-derived exosomes effectively improve functional recovery after ICH, possibly by promoting endogenous angiogenesis and neurogenesis in rats after ICH. Thus, cell-free, MSC-derived exosomes may be a novel therapy for ICH.

Lessons From the Neural Bases of Speech and Voice

2011 ◽  
Vol 21 (1) ◽  
pp. 5-14
Author(s):  
Christy L. Ludlow
Keyword(s):  
Brain Networks ◽  
Neural Substrates ◽  
Voice Behavior ◽  
Therapeutic Approaches ◽  
Neural Bases ◽  
Sound Foundation ◽  
The Brain ◽  
Normal Speech

The premise of this article is that increased understanding of the brain bases for normal speech and voice behavior will provide a sound foundation for developing therapeutic approaches to establish or re-establish these functions. The neural substrates involved in speech/voice behaviors, the types of muscle patterning for speech and voice, the brain networks involved and their regulation, and how they can be externally modulated for improving function will be addressed.

Therapeutic Approaches to Alzheimer’s Type of Dementia: A Focus on FGF21 Mediated Neuroprotection

2019 ◽  
Vol 25 (23) ◽  
pp. 2555-2568 ◽  
Author(s):  
Rajeev Taliyan ◽  
Sarathlal K. Chandran ◽  
Violina Kakoty
Keyword(s):  
Diabetes Mellitus ◽  
Protein Trafficking ◽  
Metabolic Stress ◽  
Insulin Receptors ◽  
Metabolic Dysfunction ◽  
Beneficial Effects ◽  
Glucose And Lipid Metabolism ◽  
Endocrine Hormone ◽  
Metabolic Conditions ◽  
The Brain

Neurodegenerative disorders are the most devastating disorder of the nervous system. The pathological basis of neurodegeneration is linked with dysfunctional protein trafficking, mitochondrial stress, environmental factors and aging. With the identification of insulin and insulin receptors in some parts of the brain, it has become evident that certain metabolic conditions associated with insulin dysfunction like Type 2 diabetes mellitus (T2DM), dyslipidemia, obesity etc., are also known to contribute to neurodegeneration mainly Alzheimer’s Disease (AD). Recently, a member of the fibroblast growth factor (FGF) superfamily, FGF21 has proved tremendous efficacy in diseases like diabetes mellitus, obesity and insulin resistance (IR). Increased levels of FGF21 have been reported to exert multiple beneficial effects in metabolic syndrome. FGF21 receptors are present in certain areas of the brain involved in learning and memory. However, despite extensive research, its function as a neuroprotectant in AD remains elusive. FGF21 is a circulating endocrine hormone which is mainly secreted by the liver primarily in fasting conditions. FGF21 exerts its effects after binding to FGFR1 and co-receptor, β-klotho (KLB). It is involved in regulating energy via glucose and lipid metabolism. It is believed that aberrant FGF21 signalling might account for various anomalies like neurodegeneration, cancer, metabolic dysfunction etc. Hence, this review will majorly focus on FGF21 role as a neuroprotectant and potential metabolic regulator. Moreover, we will also review its potential as an emerging candidate for combating metabolic stress induced neurodegenerative abnormalities.

The Effects of D-aspartate on Neurosteroids, Neurosteroid Receptors, and Inflammatory Mediators in Experimental Autoimmune Encephalomyelitis

2019 ◽  
Vol 19 (3) ◽  
pp. 316-325
Author(s):  
Mahdi Goudarzvand ◽  
Yaser Panahi ◽  
Reza Yazdani ◽  
Hosein Miladi ◽  
Saeed Tahmasebi ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Inflammatory Mediators ◽  
Mouse Serum ◽  
Enzyme Linked Immunosorbent Assay ◽  
Oral Gavage ◽  
Autoimmune Encephalomyelitis ◽  
Beneficial Effects ◽  
17Β Estradiol ◽  
The Brain ◽  
Experimental Autoimmune

Objective: Experimental autoimmune encephalomyelitis (EAE) is a widely used model for multiple sclerosis. The present study has been designed to compare the efficiencies of oral and intraperitoneal (IP) administration of D-aspartate (D-Asp) on the onset and severity of EAE, the production of neurosteroids, and the expression of neurosteroid receptors and inflammatory mediators in the brain of EAE mice. Methods: In this study, EAE was induced in C57BL/6 mice treated with D-Asp orally (D-Asp-Oral) or by IP injection (D-Asp-IP). On the 20th day, brains (cerebrums) and cerebellums of mice were evaluated by histological analyses. The brains of mice were analyzed for: 1) Neurosteroid (Progesterone, Testosterone, 17β-estradiol) concentrations; 2) gene expressions of cytokines and neurosteroid receptors by reverse transcription polymerase chain reaction, and 3) quantitative determination of D-Asp using liquid chromatography-tandem mass spectrometry. Further, some inflammatory cytokines and matrix metalloproteinase-2 (MMP-2) were identified in the mouse serum using enzyme-linked immunosorbent assay kits. Results: Our findings demonstrated that after D-Asp was administered, it was taken up and accumulated within the brain. Further, IP injection of D-Asp had more beneficial effects on EAE severity than oral gavage. The concentration of the testosterone and 17β-estradiol in D-Asp-IP group was significantly higher than that of the control group. There were no significant differences in the gene expression of cytokine and neurosteroid receptors between control, D-Asp-IP, and D-Asp-Oral groups. However, IP treatment with D-Asp significantly reduced C-C motif chemokine ligand 2 and MMP-2 serum levels compared to control mice. Conclusion: IP injection of D-Asp had more beneficial effects on EAE severity, neurosteroid induction and reduction of inflammatory mediators than oral gavage.

Boswellia serrata Oleo-Gum-Resin and its Effect on Memory Functions: A Review

2020 ◽  
Vol 10 (4) ◽  
pp. 355-363
Author(s):  
Mohaddese Mahboubi ◽  
Leila Mohammad Taghizadeh Kashani
Keyword(s):  
Memory Loss ◽  
Modern Medicine ◽  
Waste Materials ◽  
Boswellia Serrata ◽  
Memory Functions ◽  
Beneficial Effects ◽  
Waste Production ◽  
Nursing Mothers ◽  
Traditional Practitioners ◽  
The Brain

Background: In Iranian Traditional Medicine, Boswellia serrata oleo-gum resins were used for the treatment of "Nisyan". "Nisyan" was equivalent to a reduction of memory or forgetfulness. Objective: This review evaluates the traditional believes of B. serrata and memory and its effectiveness on memory loss. Methods: We extracted all traditional and modern information on B. serrata oleo-gum resin preparations and memory from scientific accessible resources (Google Scholar, PubMed, Springer, Science direct, Wiley), non-accessible resources and traditional books. Results: In traditional manuscripts, "Nisyan" is equal to memory loss in modern medicine and was believed to happen as the result of pouring the waste materials into the brain. Traditional practitioners treated "Nisyan" by inhibition of waste production in the brain or cleaning the brain from waste materials. They recommended using the plants with warming effects on the brain. It was believed that B. serrata had beneficial effects on memory functions and its memory enhancing effects have been the subject of pharmacological and clinical trial studies. Conclusion: Despite some documents on the effectiveness of B. serrata oleo-gum-resin on memory functions, there is gap between these investigations, especially in pregnant and nursing mothers. More investigations with large clinical trials are required to complete flaw in order to improve the therapeutic applications of B. serrata on memory functions.

Reflex Epilepsy with Hot Water: Clinical and EEG Findings, Treatment, and Prognosis in Childhood

2020 ◽  
Vol 51 (05) ◽  
pp. 336-340 ◽  
Author(s):  
Fatma Hanci ◽  
Sevim Türay ◽  
Paşa Balci ◽  
Nimet Kabakuş
Keyword(s):  
Seizure Control ◽  
Hot Water ◽  
Reflex Epilepsy ◽  
Therapeutic Approaches ◽  
Water Age ◽  
Epileptiform Discharges ◽  
Neurology Clinic ◽  
Neuromuscular Development ◽  
The Brain ◽  
International League

AbstractHot water epilepsy (HWE) is a subtype of reflex epilepsy in which seizures are triggered by the head being immersed in hot water. Hot water or bathing epilepsy is the type of reflex epilepsy most frequently encountered in our clinic. We describe our patients with HWE and also discuss the clinical features, therapeutic approaches, and prognosis. Eleven patients (10 boys, 1 girl), aged 12 months to 13 years, admitted to the pediatric neurology clinic between January 2018 and August 2019, and diagnosed with HWE or bathing epilepsy based on International League Against Epilepsy (ILAE)-2017, were followed up prospectively for ∼18 months. Patients' clinical and electroencephalography (EEG) findings and treatment details were noted. All 11 patients' seizures were triggered by hot water. Age at first seizure was between 2 months and 12 years. Seizure types were generalized motor seizures, absence, and atonic. EEG was normal in two patients, but nine patients had epileptiform discharges. Magnetic resonance imaging of the brain was performed and reported as normal (except in one case). Histories of prematurity were present in two patients, unprovoked seizures in one, and low birth weight and depressed birth in the other. Patients with HWE have normal neuromuscular development and neurological examination results, together with prophylaxis or seizure control with a single antiepileptic drug, suggesting that it is a self-limited reflex epilepsy.

scholarly journals Basal Ganglia Herniation into the Fourth Ventricle

1997 ◽  
Vol 24 (1) ◽  
pp. 62-63 ◽  
Author(s):  
Mensura Altumbabic ◽  
Marc R. Del Bigio ◽  
Scott Sutherland
Keyword(s):  
Basal Ganglia ◽  
Intracerebral Hemorrhage ◽  
Fourth Ventricle ◽  
Transtentorial Herniation ◽  
Intracerebral Bleeding ◽  
Rare Phenomenon ◽  
The Brain

ABSTRACT:Background:Transtentorial herniation of large cerebral fragments is a rare phenomenon.Method:Case StudyResults:Examination of the brain of a 35-year-old male showed massive intracerebral hemorrhage resulting in displacement of basal ganglia components into the fourth ventricle.Conclusions:Sufficiently rapid intracerebral bleeding can dissect fragments of cerebrum and displace them long distances across the tentorial opening.

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