scholarly journals Corticospinal neuroplasticity and sensorimotor recovery in rats treated by infusion of neurotrophin-3 into disabled forelimb muscles started 24 h after stroke

2018 ◽  
Author(s):  
Denise A. Duricki ◽  
Svetlana Drndarski ◽  
Michel Bernanos ◽  
Tobias Wood ◽  
Karen Bosch ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
The Body ◽  
Bold Signal ◽  
Triceps Brachii ◽  
Sensory Afferents ◽  
Adult Rats ◽  
Adult Mice ◽  
Neurotrophin 3 ◽  
High Doses ◽  
Sensorimotor Recovery

AbstractStroke often leads to arm disability and reduced responsiveness to stimuli on the other side of the body. Neurotrophin-3 (NT3) is made by skeletal muscle during infancy but levels drop postnatally and into adulthood. It is essential for the survival and wiring-up of sensory afferents from muscle. We have previously shown that gene therapy delivery of human NT3 into the affected triceps brachii forelimb muscle improves sensorimotor recovery after ischemic stroke in adult and elderly rats. Here, to move this therapy one step nearer to the clinic, we set out to test the hypothesis that intramuscular infusion of NT3 protein could improve sensorimotor recovery after ischemic cortical stroke in adult rats. To simulate a clinically-feasible time-to-treat, twenty-four hours later rats were randomized to receive NT3 or vehicle by infusion into triceps brachii for four weeks using implanted minipumps. NT3 increased the accuracy of forelimb placement during walking on a horizontal ladder and increased use of the affected arm for lateral support during rearing. NT3 also reversed sensory deficits on the affected forearm. There was no evidence of forepaw sensitivity to cold stimuli after stroke or NT3 treatment. MRI confirmed that treatment did not induce neuroprotection. Functional MRI during low threshold electrical stimulation of the affected forearm showed an increase in peri-infarct BOLD signal with time in both stroke groups and indicated that neurotrophin-3 did not further increase peri-infarct BOLD signal. Rather, NT3 induced spinal neuroplasticity including sprouting of the spared corticospinal and serotonergic pathways. Neurophysiology showed that NT3 treatment increased functional connectivity between the corticospinal tracts and spinal circuits controlling muscles on the treated side. After intravenous injection, radiolabelled NT3 crossed from bloodstream into the brain and spinal cord in adult mice with or without strokes. Our results show that delayed, peripheral infusion of neurotrophin-3 can improve sensorimotor function after ischemic stroke. Phase I and II clinical trials of NT3 (for constipation and neuropathy) have shown that peripheral, high doses are safe and well tolerated, which paves the way for NT3 as a therapy for stroke.

scholarly journals Subcutaneous neurotrophin-3 infusion induces corticospinal neuroplasticity and improvements in dexterity and walking in elderly rats after large cortical strokes

2018 ◽  
Author(s):  
Denise Duricki ◽  
Sotiris Kakanos ◽  
Barbara Haenzi ◽  
Wayman Christina ◽  
Diana Cash ◽  
...  
Keyword(s):  
Muscle Spindles ◽  
Time Frame ◽  
Sensory Function ◽  
Subcutaneous Infusion ◽  
Delayed Treatment ◽  
Neurotrophin 3 ◽  
Cortical Stroke ◽  
High Doses ◽  
And Function ◽  
Sensorimotor Recovery

AbstractThere is an urgent need for a therapy which reverses disability after stroke when initiated in a time frame suitable for the majority of new victims. Neurotrophin-3 (NT3) is a growth factor made by muscle spindles and skin which is required for the survival, development and function of locomotor circuits involving afferents from muscle and skin that mediate proprioception and tactile sensation. We set out to determine whether subcutaneous supplementation of NT3 improves sensorimotor recovery after stroke in elderly rats. We show that one-month-long subcutaneous infusion of NT3 protein induces sensorimotor recovery after cortical stroke in elderly rats. Specifically, in a randomised, blinded pre-clinical trial, we show improved dexterity, walking and sensory function in rats following cortical ischemic stroke when treatment with NT3 is initiated 24 hours after stroke. Importantly, NT-3 was given in a clinically-feasible timeframe via this straightforward route. MRI and histology showed that recovery was not due to neuroprotection, as expected given the delayed treatment. Rather, anterograde tracing showed that corticospinal axons from the less-affected hemisphere sprouted in the spinal cord from cervical levels 2 to 8. Importantly, Phase I and II clinical trials by others show that repeated, subcutaneously administered high doses of recombinant NT-3 are safe and well tolerated in humans with other conditions. This paves the way for NT-3 as a therapy for stroke.

scholarly journals Study of Acute Toxicity and Irritant Effect of Nasal Spray Naltrexone Hydrochloride

2021 ◽  
Vol 10 (2) ◽  
pp. 101-105
Author(s):  
Yu. M. Domnina ◽  
V. V. Suslov ◽  
S. A. Kedik ◽  
D. A. Akhmedova ◽  
A. P. Malkova
Keyword(s):  
Acute Toxicity ◽  
Toxic Effect ◽  
Nasal Spray ◽  
The Body ◽  
Laboratory Animals ◽  
Intragastric Administration ◽  
Naltrexone Hydrochloride ◽  
Adult Mice ◽  
High Doses ◽  
Low Dose Naltrexone

Introduction. Acute toxicity of naltrexone hydrochloride nasal spray during intragastric administration to mice and local irritant effect on rabbits was studied. At all stages of the experiment, observations were made on the General condition of the animals. The state of homeostasis was evaluated using functional, hematological and morphometric methods. According to the results of research, there was no local irritant effect on the eyes of rabbits, as well as no toxic effect of high doses of the drug on animals. Introduction. Naltrexone hydrochloride in doses of 1.5– 5 mg/day has shown its effectiveness in the treatment of a number of diseases. Due to the lack of such a "low-dose" naltrexone registered on the pharmaceutical market, we have developed the composition of the nasal spray naltrexone hydrochloride. One of the stages of our research is to study the safety of the drug being developed. The first step in this direction was to study its acute toxicity and local irritant effect.Aim. Study of acute toxicity and local irritant effect of naltrexone hydrochloride nasal spray.Materials and methods. The object of the study was a nasal spray of naltrexone hydrochloride. Acute toxicity studies were performed on outbred adult mice (females). Study of local irritant effect on Soviet chinchilla rabbits (males).Results and discussion. The study of acute toxicity showed that the drug, at a dose significantly higher than the estimated maximum daily therapeutic dose for humans, did not have a significant toxic effect on the body of laboratory animals. The presence of a local irritant effect in the studied drug was not established in the framework of the experiment.Conclusion. As part of the experiment, the drug under study did not have a local irritant or toxic effect on the animal body. The results obtained allow us to continue the development and study of the nasal spray naltrexone hydrochloride.

Effect of age on outcome in patients with cerebral stroke

2020 ◽  
pp. 41-45
Author(s):  
G. R. Kuchava ◽  
E. V. Eliseev ◽  
B. V. Silaev ◽  
D. A. Doroshenko ◽  
Yu. N. Fedulaev
Keyword(s):  
Ischemic Stroke ◽  
Neurological Deficit ◽  
Neurological Status ◽  
Statistical Correlation ◽  
Multiple Organ ◽  
The Body ◽  
Social Adaptation ◽  
Cerebral Stroke ◽  
Septic Complications ◽  
Risk Of Death

The aim of the study was to assess the course and outcome of cerebral infarction, depending on the age factor and duration of stay in the neuroblock. Materials and methods: a dynamic observation of 494 patients, men and women, aged 38–84 years with acute ischemic stroke of hemispheric localization, which were divided into the three groups depending on age, was performed. Group 1 – younger than 60 years old, group 2–60–70 years old, group 3 – older than 60 years. All patients underwent standard therapy, according to the recommendations for the treatment of ischemic stroke. The patients underwent comprehensive clinical and instrumental monitoring, which included assessment of somatic and neurological status according to the NIH‑NINDS scales at 1st, 3rd, 10th days and at discharge or death; assessment of the level of social adaptation according to the Bartel scale on 1st, 3rd, 10th days and at discharge, clinical and biochemical blood tests, computed tomography of the brain. Assessment of the quality of therapy was carried out according to specially developed maps using methods of statistical correlation analysis. Results: the most pronounced positive dynamics of neurological status was in the 1st group of patients. The regression of neurological deficit in the 2nd group was worse. The minimal dynamics of neurological deficit was in the 3rd group of patients with cerebral stroke. Most often, the death of patients with cerebral stroke occurred from the development of multiple organ disorders. Conclusions: patients over 70 years of age have the greatest risk of death, due to: a decrease in the reactivity of the body, the presence of initially severe concomitant somatic pathology in patients with admission to hospital; accession of secondary somatic and purulent‑septic complications.

scholarly journals Could Lipoxins Represent a New Standard in Ischemic Stroke Treatment?

2021 ◽  
Vol 22 (8) ◽  
pp. 4207
Author(s):  
Nikola Tułowiecka ◽  
Dariusz Kotlęga ◽  
Andrzej Bohatyrewicz ◽  
Małgorzata Szczuko
Keyword(s):  
Ischemic Stroke ◽  
Cardiovascular Diseases ◽  
Blood Brain Barrier ◽  
Inflammatory Cytokines ◽  
The Body ◽  
Brain Barrier ◽  
Lipoxin A4 ◽  
Stroke Treatment ◽  
Blood Brain ◽  
Anti Inflammatory

Introduction: Cardiovascular diseases including stroke are one of the most common causes of death. Their main cause is atherosclerosis and chronic inflammation in the body. An ischemic stroke may occur as a result of the rupture of unstable atherosclerotic plaque. Cardiovascular diseases are associated with uncontrolled inflammation. The inflammatory reaction produces chemical mediators that stimulate the resolution of inflammation. One of these mediators is lipoxins—pro-resolving mediators that are derived from the omega-6 fatty acid family, promoting inflammation relief and supporting tissue regeneration. Aim: The aim of the study was to review the available literature on the therapeutic potential of lipoxins in the context of ischemic stroke. Material and Methods: Articles published up to 31 January 2021 were included in the review. The literature was searched on the basis of PubMed and Embase in terms of the entries: ‘stroke and lipoxin’ and ‘stroke and atherosclerosis’, resulting in over 110 articles in total. Studies that were not in full-text English, letters to the editor, and conference abstracts were excluded. Results: In animal studies, the injection/administration of lipoxin A4 improved the integrity of the blood–brain barrier (BBB), decreased the volume of damage caused by ischemic stroke, and decreased brain edema. In addition, lipoxin A4 inhibited the infiltration of neutrophils and the production of cytokines and pro-inflammatory chemokines, such as interleukin (Il-1β, Il-6, Il-8) and tumor necrosis factor-α (TNF-α). The beneficial effects were also observed after introducing the administration of lipoxin A4 analog—BML-111. BML-111 significantly reduces the size of a stroke and protects the cerebral cortex, possibly by reducing the permeability of the blood–brain barrier. Moreover, more potent than lipoxin A4, it has an anti-inflammatory effect by inhibiting the production of pro-inflammatory cytokines and increasing the amount of anti-inflammatory cytokines. Conclusions: Lipoxins and their analogues may find application in reducing damage caused by stroke and improving the prognosis of patients after ischemic stroke.

scholarly journals Saturated Fat Consumption and Risk of Coronary Heart Disease and Ischemic Stroke: A Science Update

2017 ◽  
Vol 70 (1) ◽  
pp. 26-33 ◽  
Author(s):  
Joyce A. Nettleton ◽  
Ingeborg A. Brouwer ◽  
Johanna M. Geleijnse ◽  
Gerard Hornstra
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Ischemic Stroke ◽  
Saturated Fat ◽  
The Body ◽  
Epidemiological Methods ◽  
Risk Markers ◽  
Fat Consumption ◽  
Chd Risk ◽  
Important Health

At a workshop to update the science linking saturated fatty acid (SAFA) consumption with the risk of coronary heart disease (CHD) and ischemic stroke, invited participants presented data on the consumption and bioavailability of SAFA and their functions in the body and food technology. Epidemiological methods and outcomes were related to the association between SAFA consumption and disease events and mortality. Participants reviewed the effects of SAFA on CHD, causal risk factors, and surrogate risk markers. Higher intakes of SAFA were not associated with higher risks of CHD or stroke apparently, but studies did not take macronutrient replacement into account. Replacing SAFA by cis-polyunsaturated fatty acids was associated with significant CHD risk reduction, which was confirmed by randomized controlled trials. SAFA reduction had little direct effect on stroke risk. Cohort studies suggest that the food matrix and source of SAFA have important health effects.

scholarly journals Cerebral hemispheres – cerebellum – kidney interaction in patients with acute cerebral ischemia

2021 ◽  
Vol 26 (1) ◽  
pp. 90-98
Author(s):  
O.M. Kononets ◽  
O.V. Tkachenko ◽  
O.O. Kamenetska
Keyword(s):  
Nervous System ◽  
Ischemic Stroke ◽  
Brain Magnetic Resonance Imaging ◽  
Environmental Parameters ◽  
The Body ◽  
Electrolyte Balance ◽  
Vector Correlation ◽  
Vertebrobasilar System ◽  
Acute Cerebral Ischemia ◽  
The Right

The nervous system, in particular the autonomic one, is well known to constantly regulate the internal functioning of the body, adapting it to changeable external and internal environmental parameters. In particular, there is a close multiple-vector correlation between the nervous system and the kidneys. The aim of this study was to specify the mechanisms, clinical and paraclinical characteristics of the concomitant lesions of the nervous system and the kidneys in patients with acute stroke. This paper presents the case report of 215 patients, aged 70 ± 8.44, who suffered from ischemic stroke. Among them, we examined 144 women and 71 men. The patients underwent a comprehensive examination, including a detailed clinical and neurological check-up (evaluating the patients’ condition severity with the National Institutes of Health Stroke Scale (NIHSS) and the Barthel index on admission and on the 21st day of the disease), laboratory analysis (electrolyte balance, nitrogen metabolism (on admission and on the 21st day of the disease) and instrumental examination (CT scan of the brain, the follow-up brain magnetic resonance imaging). The statistical methods were used to analyze the data. In the 1st day of the disease, all the surveyed patients with right hemispheric carotid stroke and the overwhelming majority of the patients with left hemispheric carotid stroke and ischemic stroke in the vertebrobasilar system had cerebral renal syndrome, represented by renal concentration-filtration dysfunction, accompanied by the reduced glomerular filtration rate. A reliable relationship was found between the renal concentration and filtration function and the right hemispheric ischemic focus in patients with ischemic stroke, the characteristics are to be specified.

scholarly journals Changes in Adult Rats’ Testis structure Induced by Hypothyroidism and Alleviating Role of L-Carnitine

2019 ◽  
Vol 1 (4) ◽  
pp. 13-28
Author(s):  
Abdelmonem Awad Hegazy ◽  
Manal Mohammad Morsy ◽  
Rania Said Moawad ◽  
Gehad Mohammad Elsayed
Keyword(s):  
Fatty Acids ◽  
Semen Analysis ◽  
Protective Role ◽  
The Body ◽  
Albino Rats ◽  
Adult Rats ◽  
Fatty Acids Metabolism ◽  
Group 3 ◽  
Group 2

Background Hypothyroidism is a metabolic disorder affecting the functions of many tissues in the body including the testis. Testis is rich in the polyunsaturated fatty acids content and lacks strong intrinsic antioxidant system making it prone to such oxidative stress. L-carnitine (LC) regulates long chain fatty acids metabolism; and is considered a valuable antioxidant factor. Aim It was to evaluate the effect of hypothyroidism induced by propylthiouracil (PTU) on rats’ testes and the possible protective role of LC. Methods Forty-eight adult male albino rats were used in this work. The animals were divided into three groups with sixteen animals in each. Group 1 (Control): Animals were kept without medications. Group 2 (PTU-treated): was subjected to administration of PTU; while group 3 (PTU and LC) received both PTU and LC. By the end of the experiment “30 days”, blood samples were taken for hormonal assay; then animals were anaesthetized and sacrificed. Specimens were homogenized for biochemical analysis; epididymal content of each rat was obtained immediately for semen analysis. Testes’ specimens were harvested, prepared and examined by light microscope examination. Results Induced hypothyroidism was noticed to cause histopathological, morphometric and biochemical changes in rat’s testes. LC protected the testicular specimens against such changes; it also improved the seminal quality and quantity as well as testicular structure and biochemistry. Conclusion Hypothyroidism could result in hazards to the structure of testis. Fortunately co-administration of LC might reduce such hazards.

scholarly journals Place and Possibilities of the Robotic System Lokomat in the Rehabilitation of Patients After Ischemic Stroke

2019 ◽  
Vol 12 (1) ◽  
pp. 131-140
Author(s):  
Medvedev I. N.
Keyword(s):  
Ischemic Stroke ◽  
Robotic System ◽  
The Body ◽  
High Tech ◽  
Comprehensive Treatment ◽  
Common Disease ◽  
Main Task ◽  
Early Recovery ◽  
Modern Approach ◽  
Post Stroke

Ischemic stroke is still a very common disease with quite serious consequences. Modern medicine considers in this regard its main task in the curation of such patients, the maximum possible restoration of the functions of the affected brain and the volume of its control over the body. Due to the rapid development of medicine associated with the emergence of innovative technologies in the field of rehabilitation, hardware methods of rehabilitation today have gone far ahead and have in their arsenal a lot of high-tech tools. For this purpose, a search is being made for means of increasing the activity of brain cells located in the affected area. Of particular importance in this regard are the methods of rehabilitation in the early recovery period after ischemic stroke using robotic methods of mechanotherapy, one of which is the use of the Lokomat system. Among them, a prominent place is occupied by the walking training system - Lokomat, consisting of robotic orthoses and a body support device, which are combined with a treadmill. Information about the successful use of Lokomat during the rehabilitation of patients with movement disorders is still scattered, and this required their generalization and understanding. The main advantage of this system is the ability to effectively control and ensure high intensity, repeatability (reproducibility) and purposefulness of the trained movements. The convincing advantages of automated training on the Lokomat system compared to traditional rehabilitation in terms of various clinical indicators in patients with post-stroke hemiparesis have been identified. It was shown that in patients trained on the Lokomat system, a single support on the paretic leg intensified, which contributed to a more symmetrical gait. This system is more than other devices and technologies designed for learning to walk, in line with the modern approach to the restoration of impaired motor functions. The inclusion of training sessions on the Lokomat robotic system in the comprehensive treatment of patients with post-stroke hemiparesis leads to a marked improvement in movement skills. This is associated with a pronounced restructuring against the background of its use of the motor stereotype of walking, which makes it possible to increase the effectiveness of recreational activities in post-stroke patients.

Specific inhibition of response to purified protein antigens

1956 ◽  
Vol 146 (922) ◽  
pp. 18-33 ◽  
Keyword(s):  
Antibody Formation ◽  
The Body ◽  
Specific Inhibition ◽  
Protein Antigens ◽  
Bovine Albumin ◽  
Adult Mice ◽  
Immune Paralysis ◽  
Small Doses ◽  
Long Time ◽  
Stimulate Antibody

The injection of large doses of pneumococcus polysaccharides into adult mice fails to stimulate antibody formation and prevents subsequent small doses from stimulating antibody formation. This inhibition—termed immune paralysis (Felton 1949; Felton, Cameron & Prather 1941; Felton, Kauffmann, Prescott & Ottinger 1955) persists for at least 15 to 18 months. It is not possible to produce a similar effect with protein antigens. Dixon & Maurer (1953, I955 a,b ) injected very large quantities of bovine serum albumin into adult rabbits, 18 g/kg rabbit over a period of 6 weeks. Within 6 weeks of these injections four of the five animals produced antibody in response to injections of bovine albumin. It is not surprising that a long time elapsed before antibody could be detected, since during the persistence of antigen in the body, all antibody released would have combined with that vast excess of antigen.

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