scholarly journals Context of Psychotropic Drug Delivery Modulates its Neurobehavioral Effects: the Case of Methylphenidate

2017 ◽  
Author(s):  
Roy Sar-El ◽  
Gal Raz ◽  
Nitzan Lubianiker ◽  
Haggai Sharon ◽  
Talma Hendler
Keyword(s):  
Drug Targeting ◽  
Therapeutic Effects ◽  
Control Task ◽  
Non Invasive ◽  
Induction Condition ◽  
Before And After ◽  
Sites Of Action ◽  
Neurobehavioral Effects ◽  
The Brain

AbstractPharmacotherapy is substantially hindered by poor drug targeting, resulting in low specificity and efficacy. Here, we tested a novel, non-invasive targeting approach (termed functional-pharmacology), which couples drug administration with a task that activates the drug’s sites-of-action in the brain, thus possibly improving absorption and efficacy. Methylphenidate (MPH) or Placebo were administered to healthy subjects, which then performed a cognitive induction or a control task. N-Back fMRI before and after drug-task coupling measured therapeutic effects. Only following MPH, subjects that performed better in the cognitive induction task showed greater improvements in N-back performance. Moreover, only under MPH-Cognitive induction condition, there existed a significant correlation between improved recruitment of N-Back rDLPFC activation, and a concurrent improvement in task performance. Importantly, mediation analysis suggested a causal role of rDLPFC activation in these coupling effects. Our results support the functional-pharmacology concept feasibility and efficacy, hence opening a new horizon for patient-tailored, context-driven drug therapy.

scholarly journals Electro-acupuncture Alleviates METH Withdrawal-induced Spatial Memory Deficits by Restoring Astrocyte-drived Glutamate Uptake in dCA1

2020 ◽  
Author(s):  
Pengbo Shi ◽  
Zhaosu Li ◽  
Xing Xu ◽  
Jiaxun Nie ◽  
Dekang Liu ◽  
...  
Keyword(s):  
Spatial Memory ◽  
Cognitive Deficits ◽  
Glutamate Uptake ◽  
Cognitive Disorders ◽  
Memory Deficits ◽  
Therapeutic Interventions ◽  
Therapeutic Effects ◽  
Non Invasive ◽  
The Brain

ABSTRACTMethamphetamine (METH) is frequently abused drug and produces cognitive deficits. METH could induce hyper-glutamatergic state in the brain, which could partially explain METH-related cognitive deficits, but the synaptic etiology remains incompletely understood. To address this issue, we explored the role of dCA1 tripartite synapses and the potential therapeutic effects of electro-acupuncture (EA) in the development of METH withdrawal-induced spatial memory deficits in mice. We found that METH withdrawal weakened astrocytic capacity of glutamate (Glu) uptake, but failed to change Glu release from dCA3, which lead to hyper-glutamatergic excitotoxicity at dCA1 tripartite synapses. By restoring the astrocytic capacity of Glu uptake, EA treatments suppressed the hyper-glutamatergic state and normalized the excitability of postsynaptic neuron in dCA1, finally alleviated spatial memory deficits in METH withdrawal mice. These findings indicate that astrocyte at tripartite synapses might be a key target for developing therapeutic interventions against METH-associated cognitive disorders, and EA represent a promising non-invasive therapeutic strategy for the management of drugs-caused neurotoxicity.

scholarly journals Mesenchymal Stem Cell Derived Extracellular Vesicles for Repairing the Neurovascular Unit after Ischemic Stroke

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 767
Author(s):  
Courtney Davis ◽  
Sean I. Savitz ◽  
Nikunj Satani
Keyword(s):  
Ischemic Stroke ◽  
Extracellular Vesicles ◽  
Neurovascular Unit ◽  
Culture Conditions ◽  
Therapeutic Effects ◽  
Stroke Treatment ◽  
Inflammatory Molecules ◽  
The Brain

Ischemic stroke is a debilitating disease and one of the leading causes of long-term disability. During the early phase after ischemic stroke, the blood-brain barrier (BBB) exhibits increased permeability and disruption, leading to an influx of immune cells and inflammatory molecules that exacerbate the damage to the brain tissue. Mesenchymal stem cells have been investigated as a promising therapy to improve the recovery after ischemic stroke. The therapeutic effects imparted by MSCs are mostly paracrine. Recently, the role of extracellular vesicles released by these MSCs have been studied as possible carriers of information to the brain. This review focuses on the potential of MSC derived EVs to repair the components of the neurovascular unit (NVU) controlling the BBB, in order to promote overall recovery from stroke. Here, we review the techniques for increasing the effectiveness of MSC-based therapeutics, such as improved homing capabilities, bioengineering protein expression, modified culture conditions, and customizing the contents of EVs. Combining multiple techniques targeting NVU repair may provide the basis for improved future stroke treatment paradigms.

Endothelin effects in isolated, perfused lamb lungs: role of cyclooxygenase inhibition and vasomotor tone

1991 ◽  
Vol 261 (2) ◽  
pp. H443-H450 ◽  
Author(s):  
H. Toga ◽  
J. Usha Raj ◽  
R. Hillyard ◽  
B. Ku ◽  
J. Anderson
Keyword(s):  
Vasomotor Tone ◽  
Cyclooxygenase Inhibition ◽  
Group Iii ◽  
Group I ◽  
Before And After ◽  
Pulmonary Arterial ◽  
Group Ii ◽  
Sites Of Action ◽  
Arteries And Veins

We have determined the sites of action of endothelin-1 (ET) in the lamb pulmonary circulation. The influence of cyclooxygenase inhibition and baseline vasomotor tone on ET effects was also studied. Lungs of 14 lambs (6-9 wk of age, 12.1 +/- 0.6 kg body wt) were isolated and perfused with blood. Group I lungs (n = 5) were untreated, group II lungs (n = 5) were treated with indomethacin to inhibit cyclooxygenase, and group III lungs (n = 4) were treated with indomethacin and a thromboxane A2 analogue, U-46619, to elevate vasomotor tone. All lungs were perfused with constant flow in zone 3, with left atrial and airway pressures being 8 and 6 cmH2O, respectively. We measured pulmonary arterial pressure and, by the micropuncture servo-null method, pressures in 20- to 50-microns diameter subpleural venules, both before and after each dose of ET was infused (50, 100, 250, and 500 ng/kg). Group I lungs, with high baseline vasomotor tone, exhibited a biphasic response to ET; 50-100 ng/kg of ET dilated both arteries and veins, whereas 500 ng/kg of ET constricted both arteries and veins. In group II lungs with low vasomotor tone, all doses of ET caused constriction of arteries only. In group III lungs (indomethacin treated with elevated vasomotor tone), 50-100 ng/kg of ET caused dilation of arteries and veins, whereas 500 ng/kg of ET induced constriction, this time only in arteries. We conclude that ET has both dilator and constrictor effects in arteries and veins of isolated, perfused lamb lungs. ET-induced arterial and venous dilation is dependent on initial vasomotor tone but not on cyclooxygenase metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

Ventilatory responses to hypoxia in rats pretreated with nonpeptide NK1 receptor antagonist CP-96,345

1994 ◽  
Vol 76 (4) ◽  
pp. 1528-1532 ◽  
Author(s):  
G. T. De Sanctis ◽  
F. H. Green ◽  
X. Jiang ◽  
M. King ◽  
J. E. Remmers
Keyword(s):  
Ventilatory Response ◽  
Minute Ventilation ◽  
Acute Hypoxia ◽  
Frequency Component ◽  
Nk1 Receptor ◽  
Adult Rats ◽  
Nk1 Receptors ◽  
Before And After ◽  
Sites Of Action

This study reports experiments designed to evaluate the role of neurokinin-1 (NK1) receptors for substance P (SP) in the ventilatory response to acute hypoxia. Ventilation was measured by indirect plethysmography in eight unanesthetized unrestrained adult rats before and after bolus injection of 1, 5, or 10 mg/kg (ip) of CP-96,345 (Pfizer), a potent nonpeptide competitive antagonist of the SP NK1 receptor. Ventilation was measured while the rats breathed air or 8% O2–92% N2 with and without administration of SP antagonist. Pretreatment with CP-96,345 decreased the magnitude of the hypoxic response in a dose-dependent fashion. Minute ventilation in rats pretreated with CP-96,345 was reduced by 22.1% (P < 0.05) at the highest dose (10 mg/kg), largely because of an attenuation of the frequency component. Although both control and treated rats responded to hypoxia with a decrease in duration of inspiration and expiration rats pretreated with CP-96,345 displayed a smaller decrease in inspiration and expiration than control rats (P < 0.05). We have recently shown that neuropeptide-containing fibers are important for mediating the tachypnic response during acute isocapnic hypoxia in rats. The attenuation in minute ventilation at the highest dose (10 mg/kg) is comparable in magnitude to the attenuation observed with neonatal capsaicin treatment, which permanently ablates neuropeptide-containing unmyelinated fibers. Accordingly, this previously reported role of capsaicin-sensitive nerves in the hypoxic ventilatory response of rats is probably attributable to released SP acting at NK1 receptors. One of the likely sites of action of SP antagonists is the carotid body.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Evaluation on the Pharmacological Effect of Traditional Chinese Medicine SiJunZiTang on Stress-Induced Peptic Ulcers

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Chiu-Mei Chen ◽  
Chien-Ying Lee ◽  
Po-Jung Lin ◽  
Chin-Lang Hsieh ◽  
Hung-Che Shih
Keyword(s):  
Chinese Medicine ◽  
Control Group ◽  
Therapeutic Effects ◽  
Total Acidity ◽  
Peptic Ulcers ◽  
Vagus Nerves ◽  
Cure Rate ◽  
Central Neurotransmitters ◽  
The Brain

Purpose. To explore the effects of SiJunZiTang (SJZT) on central neurotransmitters and the inhibition of HCl hypersecretion, along with the role of the vagus nerve. From this, the effects of SJZT and its constituent ingredients on inhibiting stress-induced peptic ulcers will be determined.Methods. Methods used to determine SJZT's effectiveness included (1) measuring the antipeptic ulcer effects of varying combinations of the constituents of SJZT; (2) evaluations of monoamine (MA) level in the brain; and (3) measuring the effects of longer-term SJZT treatment.Results. Comparing the control and experimental groups where the rats’ vagus nerves were not cut after taking SJZT orally (500 mg/kg and 1000 mg/kg), the volume of enterogastric juice, free HCl and total acidity all reduce dose-dependently. The group administered SJZT at 1000 mg/kg showed significant reductions (P<0.05). For the experimental groups where the vagus nerves were cut, a comparison with the control group suggests that the group receiving SJZT (500 mg/kg) orally for 21 days demonstrated a cure rate of 34.53%.Conclusion. The results display a correlation between the therapeutic effects of SJZT on stress-induced peptic ulcers and central neurotransmitter levels. Further to this, SJZT can inhibit the hypersecretion of HCl in the stomach, thus inhibiting stress-induced peptic ulcers.

The role of magnetic resonance imaging in the evaluation of the functionally single ventricle before and after conversion to the Fontan circulation

2005 ◽  
Vol 15 (S3) ◽  
pp. 51-56 ◽  
Author(s):  
Pierluigi Festa ◽  
Lamia Ait Ali ◽  
Massimo Bernabei ◽  
Daniele De Marchi
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Fontan Circulation ◽  
Resonance Imaging ◽  
Full Spectrum ◽  
Non Invasive ◽  
Current Review ◽  
Future Clinical Practice ◽  
Before And After

Magnetic resonance imaging is a powerful diagnostic tool, able to give us accurate anatomical and functional insights concerning the structure of the heart, and capable of overcoming some of the drawbacks and limitations of echocardiography and catheterization. The aim of our current review is to highlight the advantages and applications of the technique in the evaluation of patients with functionally univentricular hearts before and after conversion to the Fontan circulation. Most of these patients will have undergone surgery several times in their life, with a certain body size, and with less than optimal echocardiographic windows because of the surgical scars. Moreover, vascular access is sometimes unavailable due to previous catheterizations. Furthermore, resonance imaging is non-invasive, and can be performed without sedation in patients older than 8 years. Since many of the current techniques, some of them still experimental, will be used extensively in future clinical practice, physicians should be aware of the full spectrum of capabilities of resonance imaging. We will highlight all these applications in the sections which follow.

Aldosterone in panhypopitutarism: dynamic studies and therapeutic effects in Sheehan's syndrome

1986 ◽  
Vol 112 (3) ◽  
pp. 329-335 ◽  
Author(s):  
Fawzi Bakiri ◽  
Anne M. Riondel ◽  
Moulai Benmiloud ◽  
Michel B. Vallotton
Keyword(s):  
Thyroid Hormone ◽  
Control Group ◽  
Minor Role ◽  
Therapeutic Effects ◽  
Aldosterone Secretion ◽  
Before And After ◽  
Basal Plasma ◽  
Stimulation Tests ◽  
A Minor

Abstract. To appreciate the aldosterone secretion status in panhypopituitarism, the steroid response to stimulation was studied in a homogeneous group of 20 female patients presenting with global hypopituitarism. Specific effects of glucocorticoid and thyroid hormone deficiencies were also assessed by studying the same patients before and after cortisol (F) and cortisol plus thyroid hormone (F + T) substitution. The patients were submitted to two stimulation tests before and after each treatment: the orthostasis test (O-T) and the furosemide test (Furo-T). The results obtained in the 3 situations were compared, each patient serving as her own control. Comparison was also established with the results obtained in healthy women serving as control group. Basal plasma aldosterone levels in the untreated patients were not significantly different from those of the control group (5.43 ± 0.51 vs 7.16 ±0.80 ng/100 ml, mean ± sem). They were significantly lower after F (3.91 ± 0.42) and F + T substitution (3.31 ± 0.23) than those of untreated patients and controls. Response to both stimulations was blunted in the untreated patients (O-T: 14.10 ± 2.81; Furo-T: 9.78 ± 1.35) as compared to the control group (O-T: 26.46 ± 4.67; Furo-T: 23.96 ± 3.30). F treatment did not improve the response to either tests, (O-T: 11.42 ± 2.55; Furo-T: 10.32 ± 1.23). F + T treatment normalized the orthostasis response (20.83 ± 3.59) and increased the response to furosemide which remained, however, lower (15.28 ± 1.83) than in the control group. These results are in favour of a minor role of the pituitary in the regulation of aldosterone secretion. They emphasize the role of thyroid hormones which may act partly directly, partly through their effect on renin secretion.

scholarly journals Brain aerobic glycolysis and motor adaptation learning

2016 ◽  
Vol 113 (26) ◽  
pp. E3782-E3791 ◽  
Author(s):  
Benjamin J. Shannon ◽  
Sanjeev Neil Vaishnavi ◽  
Andrei G. Vlassenko ◽  
Joshua S. Shimony ◽  
Jerrel Rutlin ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Functional Connectivity ◽  
Aerobic Glycolysis ◽  
Motor Adaptation ◽  
Resting State Functional Connectivity ◽  
Before And After ◽  
Pet Scans ◽  
The Brain ◽  
Adequate Tissue

Ten percent to 15% of glucose used by the brain is metabolized nonoxidatively despite adequate tissue oxygenation, a process termed aerobic glycolysis (AG). Because of the known role of glycolysis in biosynthesis, we tested whether learning-induced synaptic plasticity would lead to regionally appropriate, learning-dependent changes in AG. Functional MRI (fMRI) before, during, and after performance of a visual–motor adaptation task demonstrated that left Brodmann area 44 (BA44) played a key role in adaptation, with learning-related changes to activity during the task and altered resting-state, functional connectivity after the task. PET scans before and after task performance indicated a sustained increase in AG in left BA 44 accompanied by decreased oxygen consumption. Intersubject variability in behavioral adaptation rate correlated strongly with changes in AG in this region, as well as functional connectivity, which is consistent with a role for AG in synaptic plasticity.

scholarly journals Role of Microperimetry in Observation and Treatment in Patients with Macular Holes

2021 ◽  
Vol 18 (1) ◽  
pp. 90-95
Author(s):  
A. S. Zotov ◽  
A. S. Balalin ◽  
S. V. Balalin ◽  
A. M. Marukhnenko ◽  
T. G. Efremova
Keyword(s):  
Surgical Treatment ◽  
Fundus Photography ◽  
Non Invasive ◽  
Corrected Visual Acuity ◽  
Dynamic Observation ◽  
Macular Holes ◽  
Before And After ◽  
Idiopathic Macular Holes

Purpose: to assess the role of microperimetry in dynamic observation and treatment of patients with macular holes.Patients and Methods. Retrospective study of the microinvasive vitrectomy results using 25G or 27G technologies in 29 patients (29 eyes) with idiopathic macular holes (IMH). The examination included the determination of the best corrected visual acuity (BCVA), tonometry, perimetry, ultrasound biometry, optical coherence tomography, fundus photography, microperimetry.Results. After surgical treatment all patients have shown a significant improvement in BCVA and retinal photosensitivity (p < 0.05). A formula was derived for the dependence of BCVA after treatment on the initial retinal photosensitivity and the minimum IMH size, which can be applied to predict the results of surgical treatment.Conclusion. Microperimetry is a modern non-invasive examination method that allows with a higher density and resolution to localize central defects of the visual field and to carry out thorough monitoring before and after surgical treatment. The study of the retinal photosensitivity in the macular region and the minimum IMH size before treatment allow to predict BCVA in the postoperative period.

scholarly journals The Concept of Neuro- Linguistic Programming in Improving the Receptive Skills in English

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
S. Sunitha ◽  
◽  
A .Catherin Jayanthy ◽  
G. Kalaiyarasan ◽  
N. Annalakshmi
Keyword(s):  
Control Group ◽  
Brain Anatomy ◽  
School Students ◽  
Significant Difference ◽  
Before And After ◽  
Post Test ◽  
Catch Up ◽  
The Brain ◽  
Experimental Group

From the long years ago, education have been trying a proper way to improving the skills of English. Educators tried several methodologies in English to choose the better one. This paper brings out the effect of teaching Receptive skills by implementing NLP (Neuro- Linguistic Programming) in second language as English. Neuro- Linguistic Programming is one of the methods to catch up the English by giving focus on the brain anatomy. Brain anatomy can motive the creativity as well as the skills of using language. It also exist the role of Neuro Linguistic Programming in teaching the Receptive skills of English, which could make the students to improve the Receptive skills such as listening and reading. The study, in short, affirms that NLP strategies could be quite efficacious in making the students procure the skills that are indispensable in workplaces effortlessly. As it involves teaching a reading comprehension course by NLP concepts and techniques, the approach used in this study is experimental. In addition, the experimental method involves pre-and post-tests conducted before and after the course by the control group (40 students) and the experimental group (40 students). The students of the experimental community are chosen from the secondary school students. After the NLP experimentation, it was revealed from the study that there was a significant difference in the level of the experimental group in pre and post-test.

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