BDNF Function in Long-Term Synaptic Plasticity in the Dentate Gyrus In Vivo: Methods for Local Drug Delivery and Biochemical Analysis of Translation

Author(s):  
Debabrata Panja ◽  
Clive R. Bramham
2010 ◽  
Vol 99 (7) ◽  
pp. 3009-3018 ◽  
Author(s):  
Sheng-Rong Guo ◽  
Zhong-Min Wang ◽  
Ya-Qiong Zhang ◽  
Lei Lei ◽  
Jing-Min Shi ◽  
...  

2019 ◽  
Vol 224 (3) ◽  
pp. 1279-1290 ◽  
Author(s):  
Matej Vnencak ◽  
Marieke L. Schölvinck ◽  
Stephan W. Schwarzacher ◽  
Thomas Deller ◽  
Michael Willem ◽  
...  

2018 ◽  
Vol 5 (3) ◽  
pp. 175-187 ◽  
Author(s):  
O. V. Gorovtsova ◽  
T. L. Ushakova ◽  
V. G. Polyakov

Retinoblastoma is one of highly curable diseases; today the total 5-year survival rate in patients with retinoblastoma exceeds 95%. The article summarizes the current world experience on treatment of patients with intraocular retinoblastoma. The treating skills of intraocular malignant tumor in children are a balance between the patient’s life and the preservation of an eye and its visual functions. The complex and challenging task is the treatment of common intraocular retinoblastoma groups «C», «D», «E» when the large size or localization of the tumor does not allow performing the local (focal) destruction of the tumor. As a rule, in such cases neoadjuvant chemotherapy (CT) is performed at the first stage in order to reduce the size of the tumor for further focal therapy. However, the analysed data on the effectiveness of neoadjuvant CT in combination with focal or radiotherapy demonstrated the limited possibilities of the proposed therapy. Local drug delivery in cancer therapy became a real breakthrough in the organ-preserving treatment of children with large intraocular retinoblastoma. The most widely used current methods of local drug delivery are intravitreal (IVitC) and selective intra-arterial chemotherapy (SIAC) as monotherapy or in combination with neoadjuvant CT and focal therapy which significantly increased the percentage of preserved eyes without radiotherapy administration or damage to the patient survival. The review discusses the different IVitC and SIAC techniques, chemotherapy schemes, dosages of chemotherapy, immediate and long-term complications of treatment.


2020 ◽  
Vol 26 ◽  
Author(s):  
John Chen ◽  
Andrew Martin ◽  
Warren H. Finlay

Background: Many drugs are delivered intranasally for local or systemic effect, typically in the form of droplets or aerosols. Because of the high cost of in vivo studies, drug developers and researchers often turn to in vitro or in silico testing when first evaluating the behavior and properties of intranasal drug delivery devices and formulations. Recent advances in manufacturing and computer technologies have allowed for increasingly realistic and sophisticated in vitro and in silico reconstructions of the human nasal airways. Objective: To perform a summary of advances in understanding of intranasal drug delivery based on recent in vitro and in silico studies. Conclusion: The turbinates are a common target for local drug delivery applications, and while nasal sprays are able to reach this region, there is currently no broad consensus across the in vitro and in silico literature concerning optimal parameters for device design, formulation properties and patient technique which would maximize turbinate deposition. Nebulizers are able to more easily target the turbinates, but come with the disadvantage of significant lung deposition. Targeting of the olfactory region of the nasal cavity has been explored for potential treatment of central nervous system conditions. Conventional intranasal devices, such as nasal sprays and nebulizers, deliver very little dose to the olfactory region. Recent progress in our understanding of intranasal delivery will be useful in the development of the next generation of intranasal drug delivery devices.


2020 ◽  
Vol 17 (4) ◽  
pp. 354-360 ◽  
Author(s):  
Yu-Xing Ge ◽  
Ying-Ying Lin ◽  
Qian-Qian Bi ◽  
Yu-Juan Chen

Background: Patients with temporal lobe epilepsy (TLE) usually suffer from cognitive deficits and recurrent seizures. Brivaracetam (BRV) is a novel anti-epileptic drug (AEDs) recently used for the treatment of partial seizures with or without secondary generalization. Different from other AEDs, BRV has some favorable properties on synaptic plasticity. However, the underlying mechanisms remain elusive. Objective: The aim of this study was to explore the neuroprotective mechanism of BRV on synaptic plasticity in experimental TLE rats. Methods: The effect of chronic treatment with BRV (10 mg/kg) was assessed on Pilocarpine induced TLE model through measurement of the field excitatory postsynaptic potentials (fEPSPs) in vivo. Differentially expressed synaptic vesicle protein 2A (SV2A) were identified with immunoblot. Then, fast phosphorylation of synaptosomal-associated protein 25 (SNAP-25) during long-term potentiation (LTP) induction was performed to investigate the potential roles of BRV on synaptic plasticity in the TLE model. Results: An increased level of SV2A accompanied by a depressed LTP in the hippocampus was shown in epileptic rats. Furthermore, BRV treatment continued for more than 30 days improved the over-expression of SV2A and reversed the synaptic dysfunction in epileptic rats. Additionally, BRV treatment alleviates the abnormal SNAP-25 phosphorylation at Ser187 during LTP induction in epileptic ones, which is relevant to the modulation of synaptic vesicles exocytosis and voltagegated calcium channels. Conclusion: BRV treatment ameliorated the over-expression of SV2A in the hippocampus and rescued the synaptic dysfunction in epileptic rats. These results identify the neuroprotective effect of BRV on TLE model.


2015 ◽  
Vol 210 (5) ◽  
pp. 771-783 ◽  
Author(s):  
Norbert Bencsik ◽  
Zsófia Szíber ◽  
Hanna Liliom ◽  
Krisztián Tárnok ◽  
Sándor Borbély ◽  
...  

Actin turnover in dendritic spines influences spine development, morphology, and plasticity, with functional consequences on learning and memory formation. In nonneuronal cells, protein kinase D (PKD) has an important role in stabilizing F-actin via multiple molecular pathways. Using in vitro models of neuronal plasticity, such as glycine-induced chemical long-term potentiation (LTP), known to evoke synaptic plasticity, or long-term depolarization block by KCl, leading to homeostatic morphological changes, we show that actin stabilization needed for the enlargement of dendritic spines is dependent on PKD activity. Consequently, impaired PKD functions attenuate activity-dependent changes in hippocampal dendritic spines, including LTP formation, cause morphological alterations in vivo, and have deleterious consequences on spatial memory formation. We thus provide compelling evidence that PKD controls synaptic plasticity and learning by regulating actin stability in dendritic spines.


2016 ◽  
Vol 4 (48) ◽  
pp. 7845-7851 ◽  
Author(s):  
Junpeng Shi ◽  
Meng Sun ◽  
Xia Sun ◽  
Hongwu Zhang

Near-infrared persistent luminescence hollow mesoporous nanospheres have been synthesized via a template method. These nanospheres can be used as large capacity drug carriers and realize super long-term and high sensitivity tracking of drug delivery in deep tissue.


2008 ◽  
Vol 1139 ◽  
Author(s):  
Jeffrey T. Borenstein

AbstractThe emergence of BioMEMS fabrication technologies such as soft lithography, micromolding and assembly of 3D structures, and biodegradable microfluidics, are already making significant contributions to the field of regenerative medicine. Over the past decade, BioMEMS have evolved from early silicon laboratory devices to polymer-based structures and even biodegradable constructs suitable for a range of ex vivo and in vivo applications. These systems are still in the early stages of development, but the long-term potential of the technology promises to enable breakthroughs in health care challenges ranging from the systemic toxicity of drugs to the organ shortage. Ex vivo systems for organ assist applications are emerging for the liver, kidney and lung, and the precision and scalability of BioMEMS fabrication techniques offer the promise of dramatic improvements in device performance and patient outcomes.Ultimately, the greatest benefit from BioMEMS technologies will be realized in applications for implantable devices and systems. Principal advantages include the extreme levels of achievable miniaturization, integration of multiple functions such as delivery, sensing and closed loop control, and the ability of precision microscale and nanoscale features to reproduce the cellular microenvironment to sustain long-term functionality of engineered tissues. Drug delivery systems based on BioMEMS technologies are enabling local, programmable control over drug concentrations and pharmacokinetics for a broad spectrum of conditions and target organs. BioMEMS fabrication methods are also being applied to the development of engineered tissues for applications such as wound healing, microvascular networks and bioartificial organs. Here we review recent progress in BioMEMS-based drug delivery systems, engineered tissue constructs and organ assist devices for a range of ex vivo and in vivo applications in regenerative medicine.


Author(s):  
S Becker ◽  
T Xu ◽  
F Ilchmann ◽  
J Eisler ◽  
B Wolf

This paper presents a concept for an implantable micro-pump based on hydrogen- generating gas cells. The gas-generating cell is separated from the drug reservoir by an expandable latex membrane. The system offers linear drug delivery with flowrates ranging from 8 nl/s to 2 μl/s and a total delivery volume of up to 160 ml. Drugs can be dispensed over a wide backpressure range. The device is scalable based on the size of the gas-producing cell and requires no external energy source. Possible fields of application include in vivo local drug delivery for chemotherapy, diabetes, and pain management.


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