scholarly journals Effectiveness of Brain Protection With Histidine-Tryptophan-Ketoglutarate Solutions

2020 ◽  
Vol 23 (4) ◽  
pp. E510-E516
Author(s):  
Sonay Oğuz ◽  
Halil F. Aşgün ◽  
Başak Büyük

Background: Tissue-protective solutions increase resistance of cells to ischemic conditions. Especially in carotid and aortic arch surgeries where the brain perfusion is at risk, these solutions may be beneficial to prevent ischemic brain damage. This study was designed to demonstrate the effectiveness of histidine-tryptophan-ketoglutarate (HTK) solution in increasing resistance of brain tissue to ischemic conditions. Methods: Three separate randomized groups were created, each consisting of eight rabbits. The groups were called the ischemia, HTK and sham groups, respectively. In the ischemia group, temporary brain ischemia was created for 15 minutes by placing clamps on the bilateral subclavian and common carotid arteries. Then the clamps were removed, and the brain was reperfused for 30 minutes. In the HTK group, HTK solution was sent to the brain through the internal carotid artery before the same ischemia-reperfusion protocol was applied. Histopathological analyses using a visual scoring system to assess the degree of ischemic changes and the apoptotic cell index by TUNEL test were performed in all brain tissue samples. Results: Apoptotic cell indices of the HTK (20.6%) and sham (17.8%) groups were lower than the ischemia group (56.8%) (P < .05). Statistically significant differences were detected between all groups in categorical scores (P < .05). Conclusions: It was shown that less ischemic damage occurs in the brain tissue with the use of HTK solution, and it may be a candidate approach to prevent the brain from ischemic insults during cerebrovascular surgery. Further studies are required to demonstrate its exact effectiveness, in terms of dose, duration, and temperature.


2020 ◽  
Vol 11 (1) ◽  
pp. 241-250
Author(s):  
Zhenyu Li ◽  
Guangqian Ding ◽  
Yudi Wang ◽  
Zelong Zheng ◽  
Jianping Lv

AbstractTranscription factor EB (TFEB)-based gene therapy is a promising therapeutic strategy in treating neurodegenerative diseases by promoting autophagy/lysosome-mediated degradation and clearance of misfolded proteins that contribute to the pathogenesis of these diseases. However, recent findings have shown that TFEB has proinflammatory properties, raising the safety concerns about its clinical application. To investigate whether TFEB induces significant inflammatory responses in the brain, male C57BL/6 mice were injected with phosphate-buffered saline (PBS), adeno-associated virus serotype 8 (AAV8) vectors overexpressing mouse TFEB (pAAV8-CMV-mTFEB), or AAV8 vectors expressing green fluorescent proteins (GFPs) in the barrel cortex. The brain tissue samples were collected at 2 months after injection. Western blotting and immunofluorescence staining showed that mTFEB protein levels were significantly increased in the brain tissue samples of mice injected with mTFEB-overexpressing vectors compared with those injected with PBS or GFP-overexpressing vectors. pAAV8-CMV-mTFEB injection resulted in significant elevations in the mRNA and protein levels of lysosomal biogenesis indicators in the brain tissue samples. No significant changes were observed in the expressions of GFAP, Iba1, and proinflammation mediators in the pAAV8-CMV-mTFEB-injected brain compared with those in the control groups. Collectively, our results suggest that AAV8 successfully mediates mTFEB overexpression in the mouse brain without inducing apparent local inflammation, supporting the safety of TFEB-based gene therapy in treating neurodegenerative diseases.



2021 ◽  
Vol 15 ◽  
Author(s):  
Miriam Menzel ◽  
Marouan Ritzkowski ◽  
Jan A. Reuter ◽  
David Gräßel ◽  
Katrin Amunts ◽  
...  

The correct reconstruction of individual (crossing) nerve fibers is a prerequisite when constructing a detailed network model of the brain. The recently developed technique Scattered Light Imaging (SLI) allows the reconstruction of crossing nerve fiber pathways in whole brain tissue samples with micrometer resolution: the individual fiber orientations are determined by illuminating unstained histological brain sections from different directions, measuring the transmitted scattered light under normal incidence, and studying the light intensity profiles of each pixel in the resulting image series. So far, SLI measurements were performed with a fixed polar angle of illumination and a small number of illumination directions, providing only an estimate of the nerve fiber directions and limited information about the underlying tissue structure. Here, we use a display with individually controllable light-emitting diodes to measure the full distribution of scattered light behind the sample (scattering pattern) for each image pixel at once, enabling scatterometry measurements of whole brain tissue samples. We compare our results to coherent Fourier scatterometry (raster-scanning the sample with a non-focused laser beam) and previous SLI measurements with fixed polar angle of illumination, using sections from a vervet monkey brain and human optic tracts. Finally, we present SLI scatterometry measurements of a human brain section with 3 μm in-plane resolution, demonstrating that the technique is a powerful approach to gain new insights into the nerve fiber architecture of the human brain.



2019 ◽  
Vol 8 (2) ◽  
pp. 113-118
Author(s):  
Fakhri Armin ◽  
Fariba Azarkish ◽  
Ali Atash Ab Parvar ◽  
Aghdas Dehghani

Background: Renal ischemia-reperfusion (RIR) is a common clinical injury that affects the function of other remote organs such as the brain by initiating a cascade of complex and wide-ranging inflammatory responses. RIR also follows a different course in men and women. Since there is little information on the effect of RIR on the brain as a sensitive organ in both males and females, the present research was performed to investigate the effect of gender on RIR-induced brain tissue alterations in adult rats. Materials and Methods: In this study, 28 Wistar rats (14 female and 14 male rats) weighing 200 ± 20 g were divided into the following groups: 1- male sham (MS), 2- female sham (FS), 3- male ischemia (MI) with 3-hour reperfusion (ISC3hr), and 4- Female ischemia (FI) with 3-hour reperfusion (ISC3hr). Bilateral renal ischemia was induced for 45 minutes and blood samples were taken after reperfusion for the measurements of serum blood urea nitrogen (BUN), creatinine (Cr), malondialdehyde (MDA), and nitrite levels. The left kidney was removed for evaluation of MDA and tissue nitrite levels. Right kidney and brain tissue underwent histological examination. Results: Serum BUN level increased in both genders. Serum nitrite level was significantly different between both genders, meaning that it was increased in the female rats as compared to male ones. Overall brain tissue damage was significantly increased in males compared to females. Conclusion: RIR has an effect on the function and tissue of kidney and brain in both genders. Female rats are more susceptible to the nitric oxide system than the male ones. This study showed that male brain tissue was more susceptible to RIR. Therefore, gender is one of the important factors that should be considered in clinical treatments.



2015 ◽  
Vol 57 (6) ◽  
pp. 497-503 ◽  
Author(s):  
Rubens Souza de OLIVEIRA ◽  
Lanna Jamile Corrêa da COSTA ◽  
Fernanda Atanaena Gonçalves de ANDRADE ◽  
Wilson UIEDA ◽  
Luzia Fátima Alves MARTORELLI ◽  
...  

The outbreaks of rabies in humans transmitted by Desmodus rotundus in 2004 and 2005, in the northeast of the Brazilian State of Para, eastern Amazon basin, made this a priority area for studies on this zoonosis. Given this, the present study provides data on this phenomenon in an urban context, in order to assess the possible circulation of the classic rabies virus (RABV) among bat species in Capanema, a town in the Amazon basin. Bats were collected, in 2011, with mist nets during the wet and dry seasons. Samples of brain tissue and blood were collected for virological and serological survey, respectively. None of the 153 brain tissue samples analyzed tested positive for RABV infection, but 50.34% (95% CI: 45.67-55.01%) of the serum samples analyzed were seropositive. Artibeus planirostris was the most common species, with a high percentage of seropositive individuals (52.46%, 95% CI: 52.31 52.60%). Statistically, equal proportions of seropositive results were obtained in the rainy and dry seasons (c2 = 0.057, d.f. = 1, p = 0.88). Significantly higher proportions of males (55.96%, 95% CI: 48.96-62.96%) and adults (52.37%, 95% CI: 47.35-57.39%) were seropositive. While none of the brain tissue samples tested positive for infection, the high proportion of seropositive specimens indicates that RABV may be widespread in this urban area.



2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Josef Jampilek ◽  
Kamil Zaruba ◽  
Michal Oravec ◽  
Martin Kunes ◽  
Petr Babula ◽  
...  

The blood-brain barrier prevents the passage of many drugs that target the central nervous system. This paper presents the preparation and characterization of silica-based nanocarriers loaded with piracetam, pentoxifylline, and pyridoxine (drugs from the class of nootropics), which are designed to enhance the permeation of the drugs from the circulatory system through the blood-brain barrier. Their permeation was compared with non-nanoparticle drug substances (bulk materials) by means of anin vivomodel of rat brain perfusion. The size and morphology of the nanoparticles were characterized by transmission electron microscopy. The content of the drug substances in silica-based nanocarriers was analysed by elemental analysis and UV spectrometry. Microscopic analysis of visualized silica nanocarriers in the perfused brain tissue was performed. The concentration of the drug substances in the tissue was determined by means of UHPLC-DAD/HRMS LTQ Orbitrap XL. It was found that the drug substances in silica-based nanocarriers permeated through the blood brain barrier to the brain tissue, whereas bulk materials were not detected in the brain.



2018 ◽  
Vol 72 (10) ◽  
pp. 1479-1486 ◽  
Author(s):  
Gyeong Bok Jung ◽  
Sung Wook Kang ◽  
Gi-Ja Lee ◽  
Dohyun Kim

Cerebral ischemic stroke is one of the most common neurodegenerative conditions characterized by cerebral infarction, death of the brain tissue, and loss of brain function. Cerebral ischemia-reperfusion injury is the tissue damage caused when blood supply begins to the tissue after a period of ischemia or poor oxygen supply. In this study, we preliminarily investigated the biochemical changes in the brain hippocampal area, CA1, resulting from ischemia reperfusion and neuronal nitric oxide synthase (nNOS) inhibitor treatment in rats using Raman spectroscopy. A drastic spectral change was observed in the ischemia-reperfusion brain tissue; a strong dependency between the intensity of certain Raman bands was observed at the amide positions of 1276 and 1658 cm−1 and at the lipid positions of 1300 and 1438 cm−1. The spectrum of nNOS inhibitor-treated brain tissue was similar to that of the normal brain tissue, indicating that the nNOS inhibitor could protect the brain against excessive production of NO and biochemical processes dependent on it. Principal component analysis (PCA) precisely identified three classes of tissues: normal; ischemic; and nNOS inhibitor-treated. Therefore, we suggest that quantitative analysis of the changes in the brain tissue by using Raman spectroscopy with multivariate statistical technique could be effective for evaluating neuronal injury and drug effects.



Author(s):  
Mohammad Sahlabadi ◽  
Seyedvahid Khodaei ◽  
Parsaoran Hutapea

Biopsy involves removing a piece of tissues for further medical examination. Brain biopsy is generally performed using different techniques, such as open biopsy, stereotactic core biopsy, and needle biopsy. Open biopsy is the most common and the most invasive form of the brain biopsy. During the procedure, a piece of the skull is removed and the brain is exposed. Stereotactic core and needle biopsies are minimally invasive. In these procedures, a hole is usually drilled into the skull and a needle is inserted through the hole to extract the tissue. Brain biopsy has its risks and complications due to the vulnerability of the brain tissue. Although using needle or stereotactic biopsies reduce the risks, brain biopsy may cause swelling or bleeding in the brain, and in some cases, can result in infection, stroke, seizure or even coma. A needle biopsy with conventional needles involves pulling or pushing the cutting stylet inside the needle hollow body (cannula). The manual pulling and pushing procedure induces lateral movement of the needle, which increases the damage in brain tissue. The goal here is to completely remove the needle harmful lateral movement. In this work, design of smart biopsy needles is proposed and demonstrated by incorporating nitinol wires and springs to control the lateral movement of the cutting stylet. The first design comprises of two parts. The first part of the needle is a 360° tissue cutting stylet, and the second part is the cannula. The cutting stylet can slide inside the cannula and a nitinol wire is embedded at the end of the stylet and the end of the cannula. As the electric current is applied on the nitinol wire, it shrinks and pulls the cutting stylet. The second design is almost similar to the first design, but it has a 180° tissue cutting stylet with a similar actuating mechanism. The last design uses a nitinol torsion spring that is attached to the cutting stylet. It cuts tissue samples by activating the nitinol spring to rotate the cutting stylet.



2015 ◽  
Vol 17 (4) ◽  
Author(s):  
S. V. Horbachova ◽  
I. F. Bielenichev ◽  
L. I. Kucherenko

<p>Experimental acute ischemic stroke was modeled by bilateral occlusion of the common carotid arteries in rats. Antioxidant system in the brain tissue was evaluated by the activity of key enzymes of thiol and disulfide indicators<br />nitrosative stress. Simulation of acute ischemic accompanied by violation of the thiol-disulfide balance and increased nitrotyrosine levels, indicating that the development of oxidative and nitrosative stress in brain tissue. It is established<br />that the use of thiol-containing antioxidants – Thiotriazoline and Angiolin set the highest possible ratio between the levels of reduced and oxidized thiol groups and glutathione, which indicates that the active mobilization of thioldisulfide<br />system in the neutralization products of free-radical oxidation. Identified effects of the drugs used due to the presence in their structure of the thiol group, which contributes to the normalization of the glutathione system in conditions of oxidative stress.</p>



2018 ◽  
Vol 93 (4) ◽  
Author(s):  
Fabrizio Angius ◽  
Heidi Smuts ◽  
Ksenia Rybkina ◽  
Debora Stelitano ◽  
Brian Eley ◽  
...  

ABSTRACTDuring a measles virus (MeV) epidemic in 2009 in South Africa, measles inclusion body encephalitis (MIBE) was identified in several HIV-infected patients. Years later, children are presenting with subacute sclerosing panencephalitis (SSPE). To investigate the features of established MeV neuronal infections, viral sequences were analyzed from brain tissue samples of a single SSPE case and compared with MIBE sequences previously obtained from patients infected during the same epidemic. Both the SSPE and the MIBE viruses had amino acid substitutions in the ectodomain of the F protein that confer enhanced fusion properties. Functional analysis of the fusion complexes confirmed that both MIBE and SSPE F protein mutations promoted fusion with less dependence on interaction by the viral receptor-binding protein with known MeV receptors. While the SSPE F required the presence of a homotypic attachment protein, MeV H, in order to fuse, MIBE F did not. Both F proteins had decreased thermal stability compared to that of the corresponding wild-type F protein. Finally, recombinant viruses expressing MIBE or SSPE fusion complexes spread in the absence of known MeV receptors, with MIBE F-bearing viruses causing large syncytia in these cells. Our results suggest that alterations to the MeV fusion complex that promote fusion and cell-to-cell spread in the absence of known MeV receptors is a key property for infection of the brain.IMPORTANCEMeasles virus can invade the central nervous system (CNS) and cause severe neurological complications, such as MIBE and SSPE. However, mechanisms by which MeV enters the CNS and triggers the disease remain unclear. We analyzed viruses from brain tissue of individuals with MIBE or SSPE, infected during the same epidemic, after the onset of neurological disease. Our findings indicate that the emergence of hyperfusogenic MeV F proteins is associated with infection of the brain. We also demonstrate that hyperfusogenic F proteins permit MeV to enter cells and spread without the need to engage nectin-4 or CD150, known receptors for MeV that are not present on neural cells.



BBA Clinical ◽  
2016 ◽  
Vol 6 ◽  
pp. 38-44 ◽  
Author(s):  
Tommy Saing ◽  
Minette Lagman ◽  
Jeffery Castrillon ◽  
Eutiquio Gutierrez ◽  
Frederick T. Guilford ◽  
...  


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