scholarly journals Succinate Injection Rescues Vasculature and Improves Functional Recovery Following Acute Peripheral Ischemia in Rodents: A Multimodal Imaging Study

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 795
Author(s):  
Anaïs Moyon ◽  
Philippe Garrigue ◽  
Laure Balasse ◽  
Samantha Fernandez ◽  
Pauline Brige ◽  
...  
Keyword(s):  
Functional Recovery ◽  
Imaging Study ◽  
Preclinical Study ◽  
Control Group ◽  
Acute Ischemia ◽  
Peripheral Ischemia ◽  
Integrin Ligand ◽  
Angiogenic Activation ◽  
G Protein Coupled ◽  
Ischemic Muscle

Succinate influences angiogenesis and neovascularization via a hormonelike effect on G-protein-coupled receptor 91 (GPR91). This effect has been demonstrated in the pathophysiology of diabetic retinopathy and rheumatoid arthritis. To evaluate whether succinate can play a role in acute peripheral ischemia, a preclinical study was conducted with ischemic mice treated with succinate or PBS and evaluated by imaging. Acute ischemia was followed by an increased in GPR91 expression in the ischemic muscle. As assessed with LASER-Doppler, succinate treatment resulted in an earlier and more intense reperfusion of the ischemic hindlimb compared to the control group (* p = 0.0189). A microPET study using a radiolabeled integrin ligand ([68Ga]Ga-RGD2) showed an earlier angiogenic activation in the succinate arm compared to control mice (* p = 0.020) with a prolonged effect. Additionally, clinical recovery following ischemia was better in the succinate group. In conclusion, succinate injection promotes earlier angiogenesis after ischemia, resulting in a more effective revascularization and subsequently a better functional recovery.

scholarly journals Exercise Ameliorates Spinal Cord Injury by Changing DNA Methylation

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 143
Author(s):  
Ganchimeg Davaa ◽  
Jin Young Hong ◽  
Tae Uk Kim ◽  
Seong Jae Lee ◽  
Seo Young Kim ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Cortex ◽  
Functional Recovery ◽  
Treadmill Exercise ◽  
Exercise Group ◽  
Control Group ◽  
Epigenetic Changes ◽  
Cord Injury ◽  
The Brain

Exercise training is a traditional method to maximize remaining function in patients with spinal cord injury (SCI), but the exact mechanism by which exercise promotes recovery after SCI has not been identified; whether exercise truly has a beneficial effect on SCI also remains unclear. Previously, we showed that epigenetic changes in the brain motor cortex occur after SCI and that a treatment leading to epigenetic modulation effectively promotes functional recovery after SCI. We aimed to determine how exercise induces functional improvement in rats subjected to SCI and whether epigenetic changes are engaged in the effects of exercise. A spinal cord contusion model was established in rats, which were then subjected to treadmill exercise for 12 weeks. We found that the size of the lesion cavity and the number of macrophages were decreased more in the exercise group than in the control group after 12 weeks of injury. Immunofluorescence and DNA dot blot analysis revealed that levels of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in the brain motor cortex were increased after exercise. Accordingly, the expression of ten-eleven translocation (Tet) family members (Tet1, Tet2, and Tet3) in the brain motor cortex also elevated. However, no macrophage polarization was induced by exercise. Locomotor function, including Basso, Beattie, and Bresnahan (BBB) and ladder scores, also improved in the exercise group compared to the control group. We concluded that treadmill exercise facilitates functional recovery in rats with SCI, and mechanistically epigenetic changes in the brain motor cortex may contribute to exercise-induced improvements.

scholarly journals Impact of Somatosensory Training on Neural and Functional Recovery of Lower Extremity in Patients with Chronic Stroke: A Single Blind Controlled Randomized Trial

2021 ◽  
Vol 18 (2) ◽  
pp. 583
Author(s):  
Reem M. Alwhaibi ◽  
Noha F. Mahmoud ◽  
Mye A. Basheer ◽  
Hoda M. Zakaria ◽  
Mahmoud Y. Elzanaty ◽  
...  
Keyword(s):  
Physical Therapy ◽  
Lower Extremity ◽  
Functional Recovery ◽  
Intervention Group ◽  
Chronic Stroke ◽  
Post Treatment ◽  
Control Group ◽  
Stroke Patients ◽  
Significant Difference ◽  
Group Post

Recovery of lower extremity (LE) function in chronic stroke patients is considered a barrier to community reintegration. An adequate training program is required to improve neural and functional performance of the affected LE in chronic stroke patients. The current study aimed to evaluate the effect of somatosensory rehabilitation on neural and functional recovery of LE in stroke patients. Thirty male and female patients were recruited and randomized to equal groups: control group (GI) and intervention group (GII). All patients were matched for age, duration of stroke, and degree of motor impairment of the affected LE. Both groups received standard program of physical therapy in addition to somatosensory rehabilitation for GII. The duration of treatment for both groups was eight consecutive weeks. Outcome measures used were Functional Independent Measure (FIM) and Quantitative Electroencephalography (QEEG), obtained pre- and post-treatment. A significant improvement was found in the FIM scores of the intervention group (GII), as compared to the control group (GI) (p < 0.001). Additionally, QEEG scores improved within the intervention group post-treatment. QEEG scores did not improve within the control group post-treatment, except for “Cz-AR”, compared to pretreatment, with no significant difference between groups. Adding somatosensory training to standard physical therapy program results in better improvement of neuromuscular control of LE function in chronic stroke patients.

Development of Oral Chewable Tablets Containing Montelukast Nanoparticles for the Treatment of Childhood Asthma: Preclinical Study in Animal Model

2021 ◽  
Vol 11 (4) ◽  
pp. 786-791
Author(s):  
Ye Liu ◽  
Guihua Xia ◽  
Shaosheng Liu ◽  
Zhenyu Song
Keyword(s):  
Zeta Potential ◽  
Encapsulation Efficiency ◽  
Drug Loading ◽  
Crosslinking Agent ◽  
Preclinical Study ◽  
Control Group ◽  
Physical Parameters ◽  
Disintegration Time ◽  
Saturation Solubility ◽  
Chewable Tablets

The aim of the present study was to formulate oral chewable tablets of Montelukast (MTL) in the form of nanoparticles (NP’s). The MTL loaded NP’s were formulated by ionotropic external gelation method using tripolyphosphate (TPP) as crosslinking agent and Tween 60 as surfactant. NP’s were characterized for drug loading, encapsulation efficiency, surface morphology, saturation solubility, particle size, zeta potential and polydispersity index. The optimized NP formulation was used for development of chewable tablets using direct compression method. The prepared tablets were characterized for disintegration test, dissolution, thickness, hardness, friability and assay. The optimized formulation was evaluated in asthamatic animals to demonstrate the efficiency in asthama. The encapsulation efficiency of NP’s was found between 91.24 to 98.21% while drug loading was in the range of 10.09–14.25%. All formulations were found of nanosized in nature (110 to 200 nm) with excellent zeta potential (20.12 to 22.27 mV). PDI of all NP formulations were found within acceptable limit (less than 0.3). The nanoparticles were found spherical in shape with smooth surface. The saturation solubility of MTL was enhanced nearly 10 times (92 mg/ml) as compared to pure MTL saturation solubility. All physical parameters of the tablets were found within range. The optimized tablets showed disintegration time of 20 sec while other formulations showed DT in the rage of 35–57 sec. Tab1 (Optimized formulation) showed almost 100% MTL release from chewable tablets within the period of 30 min. Reduction in lung resistance (RI) was found in animals treated with Tab1. This reduction in RI was found nearly two fold and three fold as compare to MTL treated and control group animals. These observations clearly support the efficacy of chewable tablets containing nanoparticulate MTL in asthmatic animals.

Transplantation of Neural Stem/Progenitor Cells at Different Locations in Mice with Spinal Cord Injury

2014 ◽  
Vol 23 (11) ◽  
pp. 1451-1464 ◽  
Author(s):  
Hiroki Iwai ◽  
Satoshi Nori ◽  
Soraya Nishimura ◽  
Akimasa Yasuda ◽  
Morito Takano ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Progenitor Cells ◽  
Functional Recovery ◽  
Control Group ◽  
Cord Injury ◽  
Neural Stem Progenitor Cells ◽  
Neurotropic Factor ◽  
Transplantation Site

Transplantation of neural stem/progenitor cells (NS/PCs) promotes functional recovery after spinal cord injury (SCI); however, few studies have examined the optimal site of NS/PC transplantation in the spinal cord. The purpose of this study was to determine the optimal transplantation site of NS/PCs for the treatment of SCI. Wild-type mice were generated with contusive SCI at the T10 level, and NS/PCs were derived from fetal transgenic mice. These NS/PCs ubiquitously expressed ffLuc-cp156 protein (Venus and luciferase fusion protein) and so could be detected by in vivo bioluminescence imaging 9 days postinjury. NS/PCs (low: 250,000 cells per mouse; high: 1 million cells per mouse) were grafted into the spinal cord at the lesion epicenter (E) or at rostral and caudal (RC) sites. Phosphate-buffered saline was injected into E as a control. Motor functional recovery was better in each of the transplantation groups (E-Low, E-High, RC-Low, and RC-High) than in the control group. The photon counts of the grafted NS/PCs were similar in each of the four transplantation groups, suggesting that the survival of NS/PCs was fairly uniform when more than a certain threshold number of cells were transplanted. Quantitative RT-PCR analyses demonstrated that brain-derived neurotropic factor expression was higher in the RC segment than in the E segment, and this may underlie why NS/PCs more readily differentiated into neurons than into astrocytes in the RC group. The location of the transplantation site did not affect the area of spared fibers, angiogenesis, or the expression of any other mediators. These findings indicated that the microenvironments of the E and RC sites are able to support NS/PCs transplanted during the subacute phase of SCI similarly. Optimally, a certain threshold number of NS/PCs should be grafted into the E segment to avoid damaging sites adjacent to the lesion during the injection procedure.

Effects of insulin-like growth factor–I and platelet-rich plasma on sciatic nerve crush injury in a rat model

2011 ◽  
Vol 114 (2) ◽  
pp. 522-528 ◽  
Author(s):  
Erhan Emel ◽  
Selma Sönmez Ergün ◽  
Dilcan Kotan ◽  
Esra Başar Gürsoy ◽  
Yeşim Parman ◽  
...  
Keyword(s):  
Functional Recovery ◽  
Rat Model ◽  
Platelet Rich Plasma ◽  
Sensory Function ◽  
Local Administration ◽  
Control Group ◽  
Factor I ◽  
Igf I ◽  
Group 2 ◽  
Group 1

Object Local administration of insulin-like growth factor–I (IGF-I) has been shown to increase the rate of axon regeneration in crush-injured and freeze-injured rat sciatic nerves. Local administration of platelet-rich plasma (PRP) has been also shown to have a measurable effect on facial nerve regeneration after transection in a rat model. The objective of the study was to compare the effects of locally administered IGF-I and PRP on the parameters of the Sciatic Function Index (SFI), sensory function (SF), axon count, and myelin thickness/axon diameter ratio (G-ratio) in a rat model of crush-injured sciatic nerves. Methods The right sciatic nerve of Wistar albino rats (24 animals) was crushed using a Yasargil-Phynox aneurysm clip for 45 minutes. All animals were randomly divided into 3 groups: Group 1 (control group) was treated with saline, Group 2 was treated with IGF-I, and Group 3 was treated with PRP. Injections were performed using the tissue expander's injection port with a connecting tube directed at the crush-injured site. Functional recovery was assessed with improvement in the SFI. Recovery of sensory function was using the pinch test. Histopathological examination was performed 3 months after the injury. Results The SFI showed an improved functional recovery in the IGF-I–treated animals (Group 2) compared with the saline-treated animals (Group 1) 30 days after the injury. In IGF-I–treated rats, sensory function returned to the baseline level significantly faster than in saline-treated and PRP-treated rats as shown in values between SF-2 and SF-7. The G-ratios were found to be significantly higher in both experimental groups than in the control group. Conclusions This study suggests that the application of IGF-I to the crush-injured site may expedite the functional recovery of paralyzed muscle by increasing the rate of axon regeneration.

Decompressive craniectomy in a rat model of “malignant” cerebral hemispheric stroke: experimental support for an aggressive therapeutic approach

1996 ◽  
Vol 85 (5) ◽  
pp. 853-859 ◽  
Author(s):  
Arnd Doerfler ◽  
Michael Forsting ◽  
Wolfgang Reith ◽  
Christian Staff ◽  
Sabine Heiland ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Decompressive Craniectomy ◽  
Control Group ◽  
Acute Ischemia ◽  
Vessel Occlusion ◽  
Content Type ◽  
Time Points ◽  
Infarction Size ◽  
Mca Occlusion ◽  
Fine Print

✓ Acute ischemia in the complete territory of the carotid artery may lead to massive cerebral edema with raised intracranial pressure and progression to coma and death due to uncal, cingulate, or tonsillar herniation. Although clinical data suggest that patients benefit from undergoing decompressive surgery for acute ischemia, little data about the effect of this procedure on experimental ischemia are available. In this article the authors present results of an experimental study on the effects of decompressive craniectomy performed at various time points after endovascular middle cerebral artery (MCA) occlusion in rats. Focal cerebral ischemia was induced in 68 rats using an endovascular occlusion technique focused on the MCA. Decompressive cranioectomy was performed in 48 animals (in groups of 12 rats each) 4, 12, 24, or 36 hours after vessel occlusion. Twenty animals (control group) were not treated by decompressive craniectomy. The authors used the infarct volume and neurological performance at Day 7 as study endpoints. Although the mortality rate in the untreated group was 35%, none of the animals treated by decompressive craniectomy died (mortality 0%). Neurological behavior was significantly better in all animals treated by decompressive craniectomy, regardless of whether they were treated early or late. Neurological behavior and infarction size were significantly better in animals treated very early by decompressive craniectomy (4 hours) after endovascular MCA occlusion (p < 0.01); surgery performed at later time points did not significantly reduce infarction size. The results suggest that use of decompressive craniectomy in treating cerebral ischemia reduces mortality and significantly improves outcome. If performed early after vessel occlusion, it also significantly reduces infarction size. By performing decompressive craniectomy neurosurgeons will play a major role in the management of stroke patients.

scholarly journals Study of the teratogenicity of the vaccine strain of the Rubella virus «Orlov-V» (Matonaviridae: Rubivirus: Rubella virus) in experience on rhesus macaques

2021 ◽  
Vol 65 (6) ◽  
pp. 357-363
Author(s):  
I. N. Lavrentjeva ◽  
O. A. Shamsutdinova ◽  
I. I. Chugueva ◽  
D. D. Karal-ogly ◽  
O. I. Vyshemirskiy
Keyword(s):  
Blood Serum ◽  
Vaccine Strain ◽  
Rubella Virus ◽  
Rhesus Macaques ◽  
Intrauterine Infection ◽  
Preclinical Study ◽  
Wild Type Virus ◽  
Control Group ◽  
Rubella Vaccine ◽  
Congenital Rubella

Introduction. Rubella virus has pronounced teratogenic properties that can cause generalized and persistent intrauterine infection of the fetus. As a result, the control of the loss of teratogenicity inherent in «wild-type» virus strains is a necessary stage of a preclinical study of the vaccine strain for a live attenuated rubella vaccine.The purpose of the study is to comprehensively study the teratogenic properties of the vaccine strain of rubella virus «Orlov-V» in the experiment on rhesus macaques.Material and methods. Seronegative to rubella virus female rhesus macaques in early pregnancy at the age of 4–7 years (n = 13) were used in the experiment. Animals of the experimental group (n = 9) received single immunization intramuscularly with a preparation from the «Orlov-V» strain. The control group of the monkeys (n = 3) were immunized with a commercial vaccine containing Wistar RA27/3 strain. The female of the control group (n = 1) was injected with a solvent used in the rubella vaccine. Study of possible teratogenic properties of vaccine strains of rubella virus was carried out using a complex of clinical, immunological, pathomorphological and virological methods. Clinical observations were made within 3 months after the monkeys’ birth. Determination of antibody titers in the blood serum of immunized monkeys was performed in HI test on the 28th–30th day after infection. The ELISA method was applied to determine IgM antibodies in the blood serum of newborns within the first month of life. Detection of rubella virus RNA was performed by PCR with electrophoretic detection of amplicons.Results. No markers of congenital rubella infection were found in infants born from monkeys vaccinated during the pregnancy. It is shown that PCR can be an informative method to confirm the absence of teratogenic properties of vaccine strains of rubella virus.Discussion. The obtained data demonstrated that vaccine strains of the «Orlov-V» rubella virus and Wistar RA27/3 have lost their teratogenic properties. The possibility of using an alternative strategy for preclinical assessment of specific safety of antiviral vaccines including a complex of clinical, immunological, pathologic and virological methods instead of the classical pathologic method is discussed.Conclusion. The results obtained in this study showed the absence of teratogenic properties and high immunogenic activity of the vaccine strain of rubella virus «Orlov-V».

scholarly journals Influence of dibornol-HES on electrophysiological parameters in the period of restoration of blood flow in rabbit myocardium

2018 ◽  
Vol 17 (4) ◽  
pp. 6-15
Author(s):  
M. A. Vaykshnorayte ◽  
V. A. Vityazev ◽  
N. A. Vahnina ◽  
V. D. Shadrina ◽  
M. A. Torlopov ◽  
...  
Keyword(s):  
Blood Flow ◽  
Coronary Occlusion ◽  
Ischemia Reperfusion ◽  
Myocardial Damage ◽  
Water Soluble ◽  
Control Group ◽  
Acute Ischemia ◽  
30Th Minute ◽  
Dispersion Of Repolarization ◽  
Experimental Group

Objective. Dibornol-HES, a water-soluble drug based on the derivative of 2,6-diisobornyl-4-methylphenol Dibornol conjugated with hydroxyethyl starch, can reduce the occurrence and severity of arrhythmias by preventive intravenous administration, but it is unknown whether the drug could reduce the myocardial arrhythmogenicity once ischemia has developed at the developed ischemia.Materials and methods. In the model of acute ischemia / reperfusion of the rabbit heart, the effect of Dibornol-HEC (80 mg/kg body weight of the animal) on the electrophysiological indices characterizing myocardial arrhythmogenicity (global and border dispersion of repolarization) was studied during the restoration of blood flow. In the model of acute ischemia / reperfusion with 64 unipolar epicardial leads, the activation-recovery intervals were measured and global and border dispersion of repolarization in the native rabbits (control group, n = 9) and in the rabbits treated by Dibornol-HES (on the 25th minute of occlusion, the experimental group, n = 6).Results. The introduction of Dibornol-HES did not lead to a change in the electrocardiographic parameters of rabbits. By the 30th minute of the coronary occlusion on the ECG in the animals of the control and the experimental groups, the intervals RR, QT, QTc were shortened (p < 0.05). In the animals of both groups by the 30th minute of coronary occlusion, the global dispersion of repolarization increased (p < 0.05), the boundary dispersion of repolarization also increased (p < 0.05), due to the decrease in the duration of the activation-recovery intervals in the ischemic zone (p < 0.05). During the 30-minute reperfusion the magnitude of the global dispersion of repolarization did not change in animals of the both groups, and the magnitude of the border dispersion of repolarization in the control rabbits decreased (p < 0.05), while in the rabbits treated by Dibornol-HES the border dispersion of repolarization did not changed.Conclusion. In rabbits of the experimental group, the values of the global and border dispersions of repolarization did not differ from those of the animals in the control group. Therefore, the administration to Dibornol-HES just prior to reperfusion does not lead to the decrease in the dispersion of repolarization increased as a result of acute ischemic myocardial damage.

scholarly journals The role of the basolateral amygdala in the perception of faces in natural contexts

2016 ◽  
Vol 371 (1693) ◽  
pp. 20150376 ◽  
Author(s):  
Ruud Hortensius ◽  
David Terburg ◽  
Barak Morgan ◽  
Dan J. Stein ◽  
Jack van Honk ◽  
...  
Keyword(s):  
Basolateral Amygdala ◽  
Complex Structure ◽  
Dorsal Stream ◽  
Imaging Study ◽  
Control Group ◽  
Precentral Gyrus ◽  
Functional Magnetic Resonance ◽  
Context Processing ◽  
The Right

The amygdala is a complex structure that plays its role in perception and threat-related behaviour by activity of its specific nuclei and their separate networks. In the present functional magnetic resonance imaging study, we investigated the role of the basolateral amygdala in face and context processing. Five individuals with focal basolateral amygdala damage and 12 matched controls viewed fearful or neutral faces in a threatening or neutral context. We tested the hypothesis that basolateral amygdala damage modifies the relation between face and threatening context, triggering threat-related activation in the dorsal stream. The findings supported this hypothesis. First, activation was increased in the right precentral gyrus for threatening versus neutral scenes in the basolateral amygdala damage group compared with the control group. Second, activity in the bilateral middle frontal gyrus, and left anterior inferior parietal lobule was enhanced for neutral faces presented in a threatening versus neutral scene in the group with basolateral amygdala damage compared with controls. These findings provide the first evidence for the neural consequences of basolateral amygdala damage during the processing of complex emotional situations.

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