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The expression of glial cell line-derived neurothrophic factor (GDNF) transcript forms pre-(α)pro-gdnf, pre-(β)pro-gdnf, and their common region m-gdnf in the pons as well as the inferior (IC) and superior colliculi in Krushinsky–Molodkina (KM) rats and in the strain "0" was analyzed by quantitative real-time polymerase chain reaction (PCR) in the control (unstimulated KM and "0" rats) and 1.5, 4.5, and 8 h after auditory stimulation. Such stimulation induced audiogenic seizures (AS) in KM rats. Audiogenic seizure was not observed in "0" rats, which was obtained by selection for the absence of AS in a population of F2 hybrids between KM and Wistar rats not predisposed to AS. A significant drop in the level of all transcripts was observed 1.5 h after auditory stimulation in both KM and "0" rats. In most cases, the average expression of α and β isoforms and m-region 4.5 h after stimulation was greater than those after 1.5 and 8 h. At the same time, the expression of pre-(β)pro-gdnf in the IC of KM rats 4.5 h after the stimulation was significantly lower than after 1.5 or 8 h. This work presents the first demonstration of different time courses of expression of the α and β GDNF isoforms during physiological processes in genotype-specific pathology. • The GDNF isoforms in brainstem of audiogenic seizure-prone rat were examined. • Audiogenic seizure correlates with abnormal pre-(β)pro-gdnf expression in midbrain. • The diverse expression of GDNF α- and β-isoforms in vivo is firstly shown. [ABSTRACT FROM AUTHOR]

Abstract Neural network changes during aging may contribute to vulnerability and resilience to brain lesions in age-related neurological disorders, such as stroke. However, the relationship between age-related neural network features and stroke outcome is unknown. Therefore, we assessed structural and functional network status in young adult and aged rat brain, and measured the effects of simulated stroke lesions. Eleven rats underwent diffusion-weighted MRI and resting-state functional MRI at young adult age (post-natal day 88) and old age (between post-natal day 760 and 880). Structural and functional brain network features were calculated from graph-based network analysis. We performed three lesion simulations based on the brain injury pattern in frequently applied rodent stroke models, i.e. a small cortical lesion, a subcortical lesion, or a large cortical plus subcortical lesion, for which we computationally removed the involved network regions. Global network characteristics, i.e. integration and segregation, were not significantly different between the two age groups. However, we detected local differences in structural and functional networks between young adult and old rats, mainly reflected by shifts of hub regions. Stroke lesion simulations induced significant global and local network changes, characterized by lower efficiency and shifts of hub regions in structural and functional networks, which was most evident after a large cortical plus subcortical lesion. Functional and structural hub region shifts after lesion simulations differed between young adult and aged rats. Our lesion simulation study demonstrates that age-dependent brain network status affects structural and functional network reorganization after stroke, particularly involving hub shifts, which may influence functional outcome. Computational lesion studies offer a cheap and simple alternative to empirical studies and can complement or guide more complicated experimental studies in animal models and patients. Highlights • Global brain network features are stable between ages but change after focal damage. • Neural network hub nodes shift between young adulthood and old age. • Lesion-induced hub shifts differ in the young adult and aged rat brain. • Computational lesion studies allow simple assessment of post-stroke network changes. [ABSTRACT FROM AUTHOR]

The protective effect of resveratrol (RSV), a stimulator of the silent mating type information regulation 2 homolog (SIRT1), on the neurotoxicity of rat brain induced by chronic fluorosis was investigated. Thirty-two Sprague-Dawley (SD) rats were divided randomly into four groups: (i) a control group; (ii) a RSV treatment group; (iii) a fluoride-exposed group (50 ppm F- in drinking water); and (iv) a fluoride plus RSV group. The experimental period was 7 months. The protein levels of SIRT1 in the cortex and the hippocampus of the rat brains were determined by Western blotting, the SOD activity and the MDA content in the brains by biochemical methods, and the 8-OHdG content by ELISA. The spatial learning ability and the memory of the rats was examined by the Morris Water Maze test. The results showed chronic fluorosis caused changes to the brains of the rats with a reduced SIRT1 protein, elevated MDA and 8-OHdG contents, inhibited SOD activity, and, in addition, decreased learning and memory. Interestingly, RSV pretreatment attenuated the reduced SIRT1, the raised level of oxidative stress, and the lowered ability for learning and memory resulting from the chronic fluorosis. The results indicate that RSV may have a neuroprotective effect on fluoride toxicity. [ABSTRACT FROM AUTHOR]

Background: Calcitonin gene-related peptide and its receptor, consisting of receptor activity-modifying protein 1 and calcitonin receptor-like receptor, are of considerable interest because of the role they play in migraine and recently developed migraine therapies.Methods: To better understand the function of this neuropeptide, we used immunohistochemistry to determine a detailed distribution of calcitonin gene-related peptide, receptor activity-modifying protein 1 and calcitonin receptor-like receptor in the rat brain in a region of 0.5-1.5 mm lateral to the midline. We found calcitonin gene-related peptide immunoreactivity in most of the neurons of the cerebral cortex, hippocampus, cerebellum, thalamic nuclei, hypothalamic nuclei and brainstem nuclei. In contrast, receptor activity-modifying protein 1 and calcitonin receptor-like receptor immunoreactivity were found almost exclusively in the neuronal processes in the investigated regions.Conclusion: Overall, the degree of expression of calcitonin gene-related peptide and calcitonin gene-related peptide receptor components in the central nervous system is astonishingly complex and suggestive of many different brain functions, including a possible role in migraine. However, currently, the presence of calcitonin gene-related peptide and the nature of its receptors throughout the brain is an enigma yet to be solved. [ABSTRACT FROM AUTHOR]

Despite the importance of somatodendritic dopamine (DA) release in the Substantia Nigra pars compacta (SNc), its mechanism remains poorly understood. Using a novel approach combining fast‐scan controlled‐adsorption voltammetry (FSCAV) and single‐unit electrophysiology, we have investigated the mechanism of somatodendritic release by directly correlating basal (non‐stimulated) extracellular DA concentration ([DA]out), with pharmacologically‐induced changes of firing of nigral dopaminergic neurons in rat brain slices. FSCAV measurements indicated that basal [DA]out in the SNc was 40.7 ± 2.0 nM (at 34 ± 0.5°C), which was enhanced by amphetamine, cocaine, and L‐DOPA, and reduced by VMAT2 inhibitor, Ro4‐1284. Complete inhibition of firing by TTX decreased basal [DA]out, but this reduction was smaller than the effect of D2 receptor agonist, quinpirole. Despite similar effects on neuronal firing, the larger decrease in [DA]out evoked by quinpirole was attributed to cell membrane hyperpolarization and greater reduction in cytosolic free Ca2+ ([Ca2+]in). Decreasing extracellular Ca2+ also reduced basal [DA]out, despite increasing firing frequency. Furthermore, inhibiting L‐type Ca2+ channels decreased basal [DA]out, although specific Cav1.3 channel inhibition did not affect firing rate. Inhibition of sarcoplasmic/endoplasmic reticulum Ca2+‐ATPase (SERCA) also decreased [DA]out, demonstrating the importance of intracellular Ca2+ stores for somatodendritic release. Finally, in vivo FSCAV measurements showed that basal [DA]out in the SNc was 79.8 ± 10.9 nM in urethane‐anesthetized rats, which was enhanced by amphetamine. Overall, our findings indicate that although tonic somatodendritic DA release is largely independent of action potentials, basal [DA]out is strongly regulated by voltage‐dependent Ca2+ influx and release of intracellular Ca2+. Open science badges: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/. The mechanism underlying tonic dopamine (DA) release from somata and dendrites of Substantia Nigra pars compacta (SNc) neurons remains poorly understood. We have directly correlated absolute extracellular DA concentration ([DA]out) with electrophysiological activity of SNc neurons. We show that basal [DA]out is largely independent of action potentials, but is strongly regulated by intracellular Ca2+. These data shed new light on differences between somatodendritic DA release and axon terminal release, indicating that release from these sites can be controlled independently. Open Science: This manuscript was awarded with the Open Materials Badge. For more information see: https://cos.io/our-services/open-science-badges/ [ABSTRACT FROM AUTHOR]

Purpose : This article proposes a rigorous optimal control framework for the design of preparation schemes that optimize MRI contrast based on relaxation time differences. Methods : Compared to previous optimal contrast preparation schemes, a drastic reduction of the optimization parameter number is performed. The preparation scheme is defined as a combination of several block pulses whose flip angles, phase terms and inter‐pulse delays are optimized to control the magnetization evolution. Results : The proposed approach reduces the computation time of B0‐robust preparation schemes to around a minute (whereas several hours were required with previous schemes), with negligible performance loss. The chosen parameterization allows to formulate the total preparation duration as a constraint, which improves the overall compromise between contrast performance and preparation time. Simulation, in vitro and in vivo results validate this improvement, illustrate the straightforward applicability of the proposed approach, and point out its flexibility in terms of achievable contrasts. Major improvement is especially achieved for short‐T2 enhancement, as shown by the acquisition of a non‐trivial contrast on a rat brain, where a short‐T2 white matter structure (corpus callosum) is enhanced compared to surrounding gray matter tissues (hippocampus and neocortex). Conclusions : This approach proposes key advances for the design of optimal contrast preparation sequences, that emphasize their ability to generate non‐standard contrasts, their potential benefit in a clinical context, and their straightforward applicability on any MR system. [ABSTRACT FROM AUTHOR]

This study investigates the impact of maternal diabetes on the expression of α2-adrenergic and M2 muscarinic receptors in the primary visual cortex of male offspring born to diabetic rats. In adult female rats, a single dose of intraperitoneal streptozotocin (STZ) was used to induce diabetes (Diabetic group). Diabetes was controlled with insulin in the Insulin-treated group. Female rats in the control group received normal saline instead of STZ. Male newborns were euthanized at P0, P7, and P14, and the expression of α2-adrenergic and M2 muscarinic receptors in the primary visual cortex was determined using immunohistochemistry (IHC). The study showed that α2-adrenergic and M2 muscarinic receptors were significantly suppressed in all layers of the primary visual cortex of male neonates born to diabetic rats at P0, P7, and P14 compared to the control group. The highest expression was for the Con group at P14 and the lowest one was in the Dia group at P0 for both receptors. The insulin treatment in diabetic mothers modulated the expression of these receptors to normal levels in their newborns. The results demonstrate maternal diabetes decreases the expression of α2-adrenergic and M2 muscarinic receptors in the primary visual cortex of male offspring born to diabetic rats. Insulin treatment can offset these effects of diabetes. [Display omitted] • The expression levels of α2-adrenergic and M2 muscarinic receptors showed an increase with age across all groups. • There was a notable decrease in the expression of both receptors across all layers on P0, P7, and P14 in diabetic group. • Diabetic group who received insulin exhibited a restoration of receptor expression to normal levels. [ABSTRACT FROM AUTHOR]

This study quantitatively measured the changes in metabolites in the hippocampal lesions of a rat model of cuprizone-induced demyelination as detected using in vivo 7 T proton magnetic resonance spectroscopy. Nineteen Sprague Dawley rats were randomly divided into two groups and fed a normal chow diet or cuprizone (0.2%, w/w) for 7 weeks. Demyelinated hippocampal lesions were quantitatively measured using a 7 T magnetic resonance imaging scanner. All proton spectra were quantified for metabolite concentrations and relative ratios. Compared to those in the controls, the cuprizone-induced rats had significantly higher concentrations of glutamate (p = 0.001), gamma-aminobutyric acid (p = 0.019), and glutamate + glutamine (p = 0.001); however, creatine + phosphocreatine (p = 0.006) and myo-inositol (p = 0.001) concentrations were lower. In addition, we found that the glutamine and glutamate complex/total creatine (p < 0.001), glutamate/total creatine (p < 0.001), and GABA/total creatine (p = 0.002) ratios were significantly higher in cuprizone-treated rats than in control rats. Our results showed that cuprizone-induced neuronal demyelination may influence the severe abnormal metabolism in hippocampal lesions, and these responses could be caused by microglial activation, mitochondrial dysfunction, and astrocytic necrosis.

Hypertension is accompanied by oxidative stress, which can be modified by the functioning of the endocannabinoid system playing a prominent modulatory role in the brain. The present study tested whether chronic administration of the fatty acid amide hydrolase (FAAH) inhibitor [3-(3-carbamoylphenyl) phenyl]N-cyclohexylcarbamate (URB597) to rats with primary hypertension (SHR) can modify redox balance and consequently brain phospholipid metabolism. Experiments were conducted using SHRs and normotensive control Wistar–Kyoto rats treated by intraperitoneal injection with URB597 for 14 days. The biochemical parameters were assayed in the rats’ brains. Inhibition of FAAH activity by URB597 resulted in an increase in anandamide and GPR55 receptor levels, as well as a decrease in CB2 receptor expression. However, there was a simultaneous increase in Nrf2 expression, as well as Cu, Zn-SOD, GSH-Px, glutathione reductase activity, and vitamin E levels in brain tissue of SHR rats. Consequently, URB597 caused a decrease in levels of phospholipid fatty acids and MDA, and an increase in free fatty acids. Given the importance of maintaining redox balance for brain function, the results of this study point to endocannabinoids as a potential therapeutic target for preventing brain metabolic disorders in hypertension.

Reverse transcription followed by quantitative polymerase chain reaction (qRT-PCR) is a powerful and commonly used tool for gene expression analysis. It requires the right choice of stably expressed reference genes for accurate normalization. In this work, we aimed to select the optimal reference genes for qRT-PCR normalization within different brain areas during the first week following pentylenetetrazole-induced seizures in immature (P20–22) Wistar rats. We have tested the expression stability of a panel of nine housekeeping genes: Actb, Gapdh, B2m, Rpl13a, Sdha, Ppia, Hprt1, Pgk1, and Ywhaz. Based on geometric averaging of ranks obtained by four common algorithms (geNorm, NormFinder, BestKeeper, Comparative Delta-Ct), we found that the stability of tested reference genes varied significantly between different brain regions. The expression of the tested panel of genes was very stable within the medial prefrontal and temporal cortex, and the dorsal hippocampus. However, within the ventral hippocampus, the entorhinal cortex and amygdala expression levels of most of the tested genes were not steady. The data revealed that in the pentylenetetrazole-induced seizure model in juvenile rats, Pgk1, Ppia, and B2m expression are the most stable within the medial prefrontal cortex; Ppia, Rpl13a, and Sdha within the temporal cortex; Pgk1, Ppia, and Rpl13a within the entorhinal cortex; Gapdh, Ppia, and Pgk1 within the dorsal hippocampus; Rpl13a, Sdha, and Ppia within the ventral hippocampus; and Sdha, Pgk1, and Ppia within the amygdala. Our data indicate the need for a differential selection of reference genes across brain regions, including the dorsal and ventral hippocampus.

Introduction: Cardiac glycosides are widely used in critical cardiac diseases despite their unexplained mechanisms on cardio-respiratory system and other autonomic complications within both intra-uterine and post-natal life. The aim of this study is to investigate if digitalis overdose could cause a result in such complications by a destructive effect on blood-brain barrier (BBB). Methods: Twenty-five male Sprague Dawley rats weighing 300–350 g were divided into the following groups: control (n=5), sham (isotonic) (n=5), therapeutic dose (n=5), arrhythmogenic dose (n=5), and lethal dose (n=5). The animals were euthanized and their brains were extracted. The brains were histopathologically and immunohistochemically examined to evaluate BBB morphology in the superior temporal cortex. Results: One animal died because of experimental procedures on the first day. Macroscopic examination of brains revealed brain edema, subarachnoid hemorrhage (SAH), and narrowed cisterns in toxic doses of digitalis-treated animals. Brain histopathological examination of these groups revealed bloody subarachnoid and cisternal spaces, cortical arteriolar vasospasm, neurodegeneration, and even peri-arteriolar neuroglial component fragmentation; these changes induced BBB destruction in the high-dose digitalis-treated animals. Conclusion: Digitalis should not be used with overdoses if the cardio-respiratory arrhythmia is unexpectedly appearing in low doses against the possibility of defected or disrupted BBB.

Objective. To develop an immunohistochemical method for detecting histaminergic neurons in the rat hypothalamus. Materials and methods. Experiments were performed on hypothalamic specimens from 10 mongrel white male rats aged 45 and 90 days. Selective detection of histaminergic neurons on paraffin hypothalamic sections was by an immunohistochemical reaction for antibodies to monoamine oxidase type B. Results. A method for the selective detection of histaminergic neurons in the hypothalamus on paraffin sections using an immunohistochemical reaction for antibodies to monoamine oxidase type B is described. Conclusions. The method provided for detection of histaminergic neurons in paraffin sections of the hypothalamus. [ABSTRACT FROM AUTHOR]

Optical coherence tomography (OCT) is a promising medical imaging technique that uses light to capture real-time cross-sectional images from biological tissues in micrometer resolution. Commercially available optical coherence tomography systems are employed in diverse applications, including art conservation and diagnostic medicine, notably in cardiology and ophthalmology. Application of this technology in the brain may enable distinction between white matter and gray matter, and obtainment of detailed images from within the encephalon. We present, herein, the in vivo implementation of OCT imaging in the rat brain striatum. For this, two male 60-day-old rats (Rattus norvegicus, Albinus variation, Wistar) were stereotactically implanted with guide cannulas into the striatum to guide a 2.7-French diameter high-definition OCT imaging catheter (Dragonfly™, St. Jude Medical, USA). Obtained images were compared with corresponding histologically stained sections to collect imaging samples. A brief analysis of OCT technology and its current applications is also reported, as well as intra-cerebral OCT feasibility on brain mapping during neurosurgical procedures.

The chronic effects of low doses of cadmium on the distribution of soluble and filament forms of glial fibrillary acidic protein (GFAP) and their polypeptide fragments in different parts of the rat brain were investigated. Obtained results showed dose-dependent effect of cadmium on the soluble form of GFAP and more pronounced effect on the filament form and composition of the polypeptide fragments of the protein in the rat brain. Prolonged intoxication by cadmium ions in a dose of 1.0 µg/kg of body weight induced a significant decrease in soluble GFAP and an increase in the filament form in the rat brain, pointing to the development of reactive astrogliosis and the risk of neurodegeneration.

The neuroscience is continuously expanding field, and conducting experiments serves as one of the most effective approaches to enhance and broad our understanding of this fascinating field. Most of the lab work in neuroscience involves the use of animal models such as rats and mice for experiments dedicated to monitoring cerebral changes. The study:•Introduces a practical method for brain extraction without perfusion with paraformaldehyde prioritizing brain integrity and avoiding damage.•Offers a detailed, step-by-step dissection guide for different brain regions, including the hippocampus, cerebral cortex, corpus striatum, thalamus, cerebellum, and medial prefrontal cortex, from rodent brains, accompanied by high-resolution images that provide anatomical clarity.•Presents enhanced reliability, precision, and detailed anatomical descriptions. Conclusion : This study has introduced a reliable technique for brain extraction that eliminates the need for paraformaldehyde perfusion. Furthermore, a comprehensive methodology has been presented for extracting different brain regions from rodent brains., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier B.V.)

Heparan sulfate (HS), is a glycosaminoglycan (GAG) involved in various biological processes, including blood coagulation, wound healing and embryonic development. HS 3- O -sulfotransferases (3-OST), which transfer the sulfo group to the 3-hydroxyl group of certain glucosamine residues, is a key enzyme in the biosynthesis of a number of biologically important HS chains. The 3-OST-1 isoform is one of the 7 known 3-OST isoforms and is important for the biosynthesis of anticoagulant HS chains. In this study, we cloned 3-OST-1 from the rat brain by reverse transcription-polymerase chain reaction (RT-PCR). After codon optimization and removal of the signal peptide, the recombinant plasmid was transformed into Escherichia coli BL21 (DE3) to obtain a His tagged-3-OST-1 fusion protein. SDS-PAGE analysis showed that the expressed 3-OST-1 was mainly found in inclusion bodies. The 3-OST-1 was purified by Ni affinity column and refolded by dialysis. The activity of obtained 3-OST-1 was 0.04 U/mL with a specific activity of 0.55 U/mg after renaturation. Furthermore, a co-expressed recombinant plasmid pET-28a-3-OST-1 with the chaperone expression system (pGro7) was constructed and transferred to E. coli BL21 (DE3) to co-express recombinant strain E. coli BL21 (DE3)/pET-28a-3-OST-1 + pGro7. The soluble expression of 3-OST-1 was significantly improved in the co-expressed recombinant strain, with enzyme activity reaching 0.06 U/mL and having a specific activity of 0.83 U/mg. N -sulfo, N -acetylheparosan (NSNAH) was modified by the recombinant expressed 3-OST-1 and the product was confirmed by 1 H NMR showing the sulfo group was successfully transferred to NSNAH. [ABSTRACT FROM AUTHOR]

Background Various neurological and psychological disorders are related to cortical volume changes in specific brain regions, which can be measured in vivo using structural magnetic resonance imaging (sMRI). There is an increasing interest in MRI studies using rat models, especially in longitudinal studies of brain disorders and pharmacologic interventions. However, morphometric changes observed in sMRI are only meaningful if the measurements are reliable. To date, a systematic evaluation of the test-retest reliability of the morphometric measures in the rat brain is still lacking. New method We rigorously evaluated the test-retest reliability of morphometric measures derived from the voxel-based morphometry (VBM) analysis. 37 Sprague-Dawley rats were scanned twice at an interval of six hours and the gray matter volume was estimated using the VBM-DARTEL method. The intraclass coefficient, percent volume change and Pearson correlation coefficient were used to evaluate the reliability in 96 subregions of the rat brain. Results Most subregions showed excellent test-retest reliabilities within an interval of 6 h while a few regions demonstrated lower reliability, especially in the retrosplenial granular cortex. The results were consistent between different methods of reliability assessment. Comparison with existing method To the best of our knowledge, this is the first study to quantify the test-retest reliability of the VBM measurements of the rat brain. Conclusion Atlas-based cortical volume of the rat brain can be reliably estimated using the VBM-DARTEL method in most subregions. However, findings in subregions with lower reliability must be interpreted with caution. [ABSTRACT FROM AUTHOR]

Smad proteins are known to transduce the action of TGF-β superfamily proteins including TGF-βs, activins, and bone morphogenetic proteins (BMPs). In this study, we examined the expression of Smad1, -2, -3, -4, -5, and -8 mRNA in the rat brain by means of RT-PCR and in situ hybridization (ISH). In addition, we examined the nuclear accumulation of Smad1, -2, -3, -5, and -8 proteins after intracerebroventricular injection of TGF-β1, activin A, or BMP6 with immunohistochemistry to investigate whether TGF-β, activin, and/or BMP activate Smads in the rat brain. RT-PCR analysis revealed that Smad1, -2, -3, -4, -5, and -8 mRNA was expressed in the brain and that the Smad3 and Smad8 mRNA differed in the expression level between brain regions. For example, there were high levels of expression of Smad3 mRNA in the cerebral cortex, caudate putamen/globus pallidus, and cerebellum, but low levels in the thalamus and midbrain. Expression of Smad8 mRNA was higher in the midbrain, cerebellum, and pons/medulla oblongata in comparison to the olfactory bulb, cerebral cortex, caudate putamen/globus pallidus, hippocampus/dentate gyrus, and thalamus. ISH signals for Smad1 mRNA were widely detected in the brain except for a small number of regions including the olfactory tubercle, posterior region of hypothalamus, and cerebellar nuclei. ISH signals for Smad2 mRNA were abundantly observed in several brain regions including the olfactory bulb, piriform cortex, basal ganglia, cingulate cortex, epithalamus, including the pineal gland and medial habenular nuclei, hypothalamus, inferior colliculi of the midbrain, and some nuclei in the pons, cerebellar cortex, and choroid plexus. ISH signals for Smad3 mRNA were also abundantly observed in several brain regions. Especially strong signals for Smad3 mRNA were observed in the olfactory tubercle, piriform cortex, basal ganglia, dentate gyrus, and cingulate cortex. ISH signals for Smad5 and Smad8 mRNA were restricted to a small number of brain regions, the signal intensity of which was weak. ISH signals for Smad4 mRNA were detected in all regions examined. Intracerebroventricular injection of activin A induced nuclear accumulation of Smad2 and Smad3 immunoreactivity in neurons. In contrast, intracerebroventricular injection of TGF-β1 or BMP6 did not induce nuclear accumulation of the immunoreactivity for any Smad in neurons. These results suggest that activin-Smad signaling plays an important role in brain homeostasis. [ABSTRACT FROM AUTHOR]

Abstract: The serious damage of ischemia to brain function has attracted extensive attention. As two of vital signal molecules, development of biosensors for monitoring of hydrogen peroxide (H2O2) and pH in vivo is significant to understand the roles of H2O2 and pH playing in rat brain followed by ischemia. Herein, a selective and accuracy ratiometric electrochemical biosensor was developed for quantifying H2O2 and pH through both current and potential outputs in a rat brain upon ischemia. Catalase (Cat) was first employed as a specific recognition element for both H2O2 and pH. Meanwhile, an inner reference molecule, ferrocene (Fc), independent of H2O2 and pH, was used as a built‐in correction to improve the accuracy. The reduction peak current of Cat increased with increasing concentration of H2O2 from 1.0 to 230 μM. Meanwhile, the peak potential negatively shifted with increasing pH from 5.91 to 7.81, resulting in determination of H2O2 and pH. Thus, combined with the remarkable analytical performance of the developed biosensor and the desirable biocompatibility of carbon fibre microelectrode (CFME), a direct and reliable approach was established to monitoring H2O2 and pH in the microdialysates collected from rat brain followed by cerebral ischemia. [ABSTRACT FROM AUTHOR]

Abstract: In vivo monitoring of dopamine (DA) in cerebral nervous system with no traumatic brain injury is still a challenging work for reliably evaluating the role that DA plays in physical and cognitive functionality. In this work, to reduce the traumatic injury on the brain tissue, we develop a glass‐sealed Au nanoelectrode (GSNE) with nanoscale physical dimention for cerebral DA detection. First, an Au microwire was sealed into the pre‐thinned silica capillary. Then, the obtained Au/capillary assembly was pulled into two tips followed by polishing away the excess glass to expose the Au nanotip. The morphology of GSNE was characterized by scanning electron microscopy and transmission electron microscopy. The results showed that this nanoelectrode can be quickly fabricated with high reproducibility. By further electrodepositing cluster‐like gold nanostructure on GSNE and modifying Nafion, amperometric detection of DA with high sensitivity and good selectivity were achieved on the Nafion‐modified Au/GSNE. Moreover, the Nafion‐modified Au/GSNE possessed advantages of easy tissue insertion and minimum tissue disturbance. Thus, the developed electrochemical nanosensor was successfully used for amperometrically monitoring DA level in the striatum of anesthetic rats. [ABSTRACT FROM AUTHOR]

Herein, we report a facile yet effective fluorescent nanosensor for the direct, selective and sensitive determination of cerebral Cu 2+ in the rat brain microdialysate. The fluorescent nanosensor is constructed by utilizing the strong fluorescent graphene quantum dots (GQDs) as the fluorescent signaling output, which were synthesized via chemical oxidation from 3D nanomesh graphene frameworks (NGFs). Initially, the as-prepared GQDs displays a uniform size with lateral size below 5 nm is observed to exhibit photoluminescence properties. The subsequent addition of Cu 2+ into the GQDs mixture results in the significant quenching of the fluorescence of GQDs. The quenching degree of Cu 2+ towards GQDs is highly sensitive to the concentration of Cu 2+ and shows a linear relationship for Cu 2+ within the range from 0.1 μM to 1.0 μM with a limit of detection (LOD) of 0.067 μM which substantially enables the GQDs as a nanosensor for Cu 2+ . Moreover, the as-fabricated nanosenor displays a high specificity for Cu 2+ irrespective of the coexistence of other metal ions, amino acids, and biological substance that endogenously existed in the rat brain and has been employed to successfully determination of Cu 2+ in rat brain with the basal value of 2.21 ± 0.76 μM (n = 3). [ABSTRACT FROM AUTHOR]

Over the last years, many studies reported on the antioxidant effects of ferulic acid (FA) in preclinical models of dementia through the activation of the heme oxygenase/biliverdin reductase (HO/BVR) system. However, only a few studies evaluated whether FA could improve neurological function under milder conditions, such as psychological stress. The aim of this study was to investigate the effects of FA (150 mg/kg intraperitoneal route) on cognitive function in male Wistar rats exposed to emotional arousal. Animals were randomly assigned to two experimental groups, namely not habituated or habituated to the experimental context, and the novel object recognition test was used to evaluate their cognitive performance. The administration of FA significantly increased long-term retention memory in not habituated rats. Ferulic acid increased the expression of HO-1 in the hippocampus and frontal cortex of not habituated rats only, whereas HO-2 resulted differently modulated in these cognitive brain areas. No significant effects on either HO-1 or HO-2 or BVR were observed in the cerebellum of both habituated and not habituated rats. Ferulic acid activated the stress axis in not habituated rats, as shown by the increase in hypothalamic corticotrophin-releasing hormone levels. Pre-treatment with Sn-protoporphyrin-IX [0.25 μmol/kg, intracerebroventricular route (i.c.v.)], a well-known inhibitor of HO activity through which carbon monoxide (CO) and biliverdin (BV) are generated, abolished the FA-induced improvement of cognitive performance only in not habituated rats, suggesting a role for HO-derived by-products. The CO-donor tricarbonyldichlororuthenium (II) (30 nmol/kg i.c.v.) mimicked the FA-related improvement of cognitive skills only in not habituated rats, whereas BV did not have any effect in any group. In conclusion, these results set the stage for subsequent studies on the neuropharmacological action of FA under conditions of psychological stress. [ABSTRACT FROM AUTHOR]

Purpose A systematic method is proposed for optimizing a promising preclinical arterial spin labeling (ASL) sequence based on the use of a train of adiabatic radiofrequency pulses labeling successive boli of blood water. Methods The sequence optimization is performed and evaluated using brain imaging experiments in mice and in rats. It involves the investigation of several parameters, ranging from the number of adiabatic pulses and labeling duration to the properties of the adiabatic hyperbolic secant pulses (ie, amplitude and frequency modulation). Results Species-dependent parameters are identified, allowing for robust fast optimization protocols to be introduced. The resulting optimized multiple boli ASL (mbASL) sequence provides with significantly higher average signal-to-noise ratios (SNR) per voxel volume than currently encountered in ASL studies (278 mm−3 in mice and 172 mm−3 in rats). Comparing with the commonly used flow-sensitive alternating inversion recovery technique (FAIR), mbASL-to-FAIR SNR ratios reach 203% for mice and 725% for rats. Conclusion When properly optimized, mbASL can offer a robust, high SNR ASL alternative for rodent brain perfusion studies Magn Reson Med 79:1020-1030, 2018. © 2017 International Society for Magnetic Resonance in Medicine. [ABSTRACT FROM AUTHOR]

Angelicae Pubescentis Radix (APR) is a widely-used traditional Chinese medicine. Pharmacological studies have begun to probe its biological activities on neurological disorders recently. To assess the brain penetration and distribution of APR, a validated ultra-performance liquid chromatography tandem mass spectrometry method was applied to the simultaneous determinations of the main coumarins from APR in the rat cerebrospinal fluid (CSF) and brain after oral administration of APR extract, including psoralen, xanthotoxin, bergapten, isoimperatorin, columbianetin, columbianetin acetate, columbianadin, oxypeucedanin hydrate, angelol B, osthole, meranzin hydrate and nodakenetin. Most of the tested coumarins entered the rat CSF and brain quickly, and double-peak phenomena in concentration-time curves were similar to those of their plasma pharmacokinetics. Columbianetin had the highest concentration in the CSF and brain, while psoralen and columbianetin acetate had the largest percent of CSF/plasma and brain/plasma, indicating that these three coumarins may be worthy of further research on the possible nervous effects. Correlations between the in vivo brain distributions and plasma pharmacokinetics of these coumarins were well verified. These results provided valuable information for the overall in vivo brain distribution characteristics of APR and also for its further studies on the active substances for the central nervous system. [ABSTRACT FROM AUTHOR]

A folded four-ring quadrature birdcage coil was designed and constructed with a double-tune configuration of an outer high-pass coil for 1 H (400 MHz) and inner low-pass coil for 23 Na (105.72 MHz at 9.4 T). The coil was evaluated on the bench and in the scanner, comparing its performance with that of single-tuned coils and a large four-ring coil. All coils were tuned and matched and the isolation between two quadrature ports was found to be better than −13.7 dB for 1 H and −27 dB for 23 Na. Signal-to-noise ratios (SNRs) were calculated and 23 Na flip angle maps were acquired. 23 Na SNR of the folded four-ring reached ∼93% of that obtained with the single-tuned coil. A set of in vivo 1 H and 23 Na axial images to cover the whole rat brain were obtained. The performance of the folded four-ring coil and its benefit for 23 Na imaging experiments have been demonstrated. This proposed four-ring coil could avoid length restrictions, e.g. the shoulders, by folding the outer rings vertically. This facilitates the construction of double-tuned four-ring birdcage coils just to fit the head, leading to higher filling factors and better SNR. [ABSTRACT FROM AUTHOR]

High glycine (GLY) levels have been suggested to induce neurotoxic effects in the central nervous system of patients with nonketotic hyperglycinemia (NKH). Since the mechanisms involved in the neuropathophysiology of NKH are not totally established, we evaluated the effect of a single intracerebroventricular administration of GLY on the content of proteins involved in neuronal damage and inflammatory response, as well as on the phosphorylation of the MAPK p38, ERK1/2, and JNK in rat striatum and cerebral cortex. We also examined glial fibrillary acidic protein (GFAP) staining, a marker of glial reactivity. The parameters were analyzed 30 min or 24 h after GLY administration. GLY decreased Tau phosphorylation in striatum and cerebral cortex 30 min and 24 h after its administration. On the other hand, synaptophysin levels were decreased in striatum at 30 min and in cerebral cortex at 24 h after GLY injection. GLY also decreased the phosphorylation of p38, ERK1/2, and JNK 30 min after its administration in both brain structures. Moreover, GLY-induced decrease of p38 phosphorylation in striatum was attenuated by N-methyl-d-aspartate receptor antagonist MK-801. In contrast, synuclein, NF-κB, iκB, inducible nitric oxide synthase and nitrotyrosine content, and GFAP immunostaining were not altered by GLY infusion. It may be presumed that the decreased phosphorylation of MAPK associated with alterations of markers of neuronal injury induced by GLY may contribute to the neurological dysfunction observed in NKH. [ABSTRACT FROM AUTHOR]