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Toluidine blue staining. (A) Size and staining of the neurons and Nissl bodies were uniform in the water group. (B) Size and staining of neurons varied, with Nissl bodies disappearing (arrow) in the water-TBI group. (C) Size of neurons also varied with mass aggregation Nissl bodies (arrow) in the EtOH group. (D) Dark neurons (arrow) were observed in the EtOH-TBI group. Toluidine blue staining, ×400.
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We investigated the axonal morphological changes and expression of both tau protein and β-APP following concussion to the medulla oblongata, in a rat model of chronic alcoholism.
Fifty-nine male Sprague-Dawley rats were randomly divided into EtOH, EtOH-TBI and control groups (water group, water-TBI group). To establish chronic alcoholic rats, rats...
Contexts in source publication
Context 1
... fibres were observed in the medulla oblongata of the EtOH-TBI group, water-TBI group and EtOH group, especially in alco- holic rats after injury. Size and staining of neurons and Nissl bodies were non-uniform in all groups except rats fed with water. In the EtOH-TBI group, mass aggregation of Nissl bodies as well as dark neurons was observed (Fig. ...
Context 2
... medulla oblongata tau IOD sum value of the EtOH group was reduced compared with that of water group (P < 0.05), whereas the tau IOD value of the EtOH-TBI group was higher (P < 0.05) than that of the EtOH group. However, the difference between the water-TBI group and water group was not significant (P > 0.05) ( Supplementary Fig. S2, Fig. 5). ...
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Citations
... The cell body of the neuron-like cells was stained with toluidine blue following the protocol of Luo [41,44], with minor modifications, and the protocol is given in supplementary data section F. The nissil bodies of the neurons were stained with neutral red, and the brief procedure is given in the supplementary data section G. The standardized protocol was followed with a few modifications [42,45]. ...
... PubChem (https://pubchem.ncbi.nlm.nih.gov/). The preparation of receptor, ligand, and grid optimization was performed in AutoDock Tool [44,47] and AutodockVina tools [45,48]. In brief, the receptor (protein) PDB structure was fed into AutoDock Tools (ADT), and co-crystallized complex protein chains, heteroatoms, and water molecules were removed. ...
PurposeTo date to repair and restore the neurons in neurodegenerative disorders, numerous approaches are addressed, but the retaining activities of those cells were not well distinguished. The lack of effective treatments, including scarce disease-modifying therapies, urged experimenting with cell therapies, including mesenchymal stem cells.Methods
Wnt inhibitors Quercetin and Niclosamide were treated to mouse mesenchymal stem cells (mMSCs) and were tested for potential trans-differentiation towards neuronal-like cells by analysis of morphology, neuronal cell staining, and neuronal-specific gene expression patterns. Molecular docking of Quercetin and Niclosamide was performed with Nestin, MAP2, NeuN, BDNF and ChaT neuronal proteins.ResultsThe differentiation potential of mMSCs was confirmed by the cell body, nissil body formation, and gene expression analysis of neuronal-specific genes like Nestin, BDNF, CHAT, MAP2, and NeuN. The docking analysis showed that Quercetin and Niclosamide had a better binding affinity with ChaT. The morphological similarities and significant upregulation in neurite growth potential after treatment was an added confirmation of trans-differentiation potential. These cell-permeable Wnt inhibitors have been exhibited to facilitate cell reprogramming and promote neural differentiation of mMSCs.Conclusion
The mechanisms underlying neurodegeneration are poorly understood, thus making the target-based drug screening strategies difficult. With the realization of inducing easily accessible cells, such as mMSCs, to inaccessible cells lost in degenerative diseases, these results may contribute to potential cell replacement therapies. However, further studies are yet to be carried out to understand the mechanism of these small molecules in modulating the Wnt signalling pathway aiding in trans-differentiation of MSCs to the neuronal cells.
... The sections in the lateral 1.9-2.4 mm of the rat medulla oblongata were collected for histological and immunohistochemical studies according to Luo et al. [15]. Sections of Medulla oblongata were fixed in 10% buffered formalin (pH 7.4) for 48 hours. ...
... Small parts of the medulla oblongata (1 mm×1 mm×2 mm) at the lateral 1.9-2.4 mm level from the center [15] were taken and immediately immersed in buffered formol glutaraldehyde (pH=7.3). After an hour, the medulla oblongata segments were cut into about 1 mm 3 specimens and fixed in buffered formol glutaraldehyde, pH 7.3, for 24 hours at 4°C and routinely osmicated in 1% osmium tetroxide. ...
Previous studies have shown that cypermethrin (CYP), a broad spectrum pesticide has a teratogenic effect on rat offspring born to an exposed dam with no information on its effect on the development of the brain. To the best of our knowledge, this research is the first attempt to study the postnatal development medulla oblongata of rat offspring exposed to CYP during the perinatal period and the possible neuroprotective role of melatonin. The offspring of treated female rats were organized into control, melatonin (1 mg/kg/day orally); CYP (12 mg/kg/day orally); and CYP/melatonin groups. The mothers received treatments from day 6 of gestation until day 21 after birth. At Postnatal days 7 and 21, the animals were sacrificed and their medulla oblongata was removed and subjected to histological, immunohistochemical, and electron microscopic studies. CYP induced neuronal degeneration by chromatolysis and pyknosis. Nuclear changes, cytoplasmic vacuolation, damage mitochondria, and breakdown of RER were also detected. Reduction of microtubule-associated protein-2 (MAP-2), myelin basic protein (MBP), and oligodendrocyte transcription factor expressions and increment of glial fibrillary acidic protein expression in the medulla oblongata of the developing rats were observed. On the other hand, melatonin led to an obvious improvement of the injured medulla oblongata tissues and ameliorating the damaging effects of CYP. In conclusion, melatonin has protected rats against CYP-induced histopathological and immunohistochemical changes. This may be due to the protection of MAP-2, conservation of MBP, an increment of oligodendrocytes, and alleviation of astrogliosis.
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... The patients with chronic alcoholism display -as an observation factor resulting from the experience of our casuistry (from the Neuromuscular Recovery Clinic of the lesions of the intraneuraxial white matter are produced (without being correlated with significant structural changes in the lipids of myelin composition) [48]. The entire histopathological and functional encephalic picture resembles a process of accelerated neural aging [48]. ...
... A physiopathological neurotoxic ethanolic mechanism can also be encountered in the case of Wernicke encephalopathy (consequence of the thiamin deficiency resulting from malnutrition that occurs in chronic ethanol abuse) [48]. In this case, in addition to the psycho-cognitive disturbances (included in the Korsakoff syndrome), database (not ISI indexed) and 23 in the PMC of which 16 ISI indexed (Table 4 of Annex I). ...
We found differences related to the neuro-functional deficiency and clinical progress, among non-consumers and chronic consumers of ethanol, with recent traumatic spinal cord injury (SCI). We present a synthesis of related data on lesion mechanisms in post-traumatic myelogenous disorders, namely some of the alcohols and their actions on the nervous system, with details on the influences exerted, in such afflictions, by the chronic consumption of ethanol. The subject is not frequently approached - according to a literature review with systematic elements, which we have done before - thus constituting a niche that deserves to be further explored. The applicative component of the article highlights statistical data resulted from a retrospective study regarding the specialized casuistry from the Neuromuscular Recovery Clinic of the "Bagdasar Arseni" Emergency Clinical Hospital, following the comparative analysis of two groups of patients with recent SCI: non-consumers - the control group (n=780) - and chronic ethanol consumers - the study group (n=225) - with the addition of a prospective pilot component. Data processing has been achieved with SPSS 24. The American Spinal Injury Association Impairment Scale (AIS) mean motor scores differ significantly (tests: Mann-Whitney and t) between the control and study group in favor of the second, both at admission (p<0.001) and at discharge (p<0.001). AIS mean sensitive scores differ between the two lots, and also in favor of the study, but statistically significant only at discharge (p=0.048); the difference at admission is not significant (p=0.51) - possibly because of alcoholic-nutritional polyneuropathy. These findings, with numerous related details, later presented in the text, are surprising, which requires further studies and attempts of understanding.
... However, recent findings using nonhuman animal models of alcoholism may help to explain alcohol induced white matter deficits. Animal studies have provided morphological evidence that chronic alcohol exposure can cause damage not only to nerve cells but also to nerve fibers [38][39][40]. ...
Excessive alcohol consumption is associated with brain aberrations, including abnormalities in frontal and limbic brain regions. In a prior diffusion tensor magnetic resonance imaging (dMRI) study of neuronal circuitry connecting the frontal lobes and limbic system structures, we demonstrated decreases in white matter fractional anisotropy in abstinent alcoholic men. In the present study, we examined sex differences in alcoholism-related abnormalities of white matter connectivity and their association with alcoholism history. The dMRI scans were acquired from 49 abstinent alcoholic individuals (26 women) and 41 nonalcoholic controls (22 women). Tract-based spatial statistical tools were used to estimate regional FA of white matter tracts and to determine sex differences and their relation to measures of alcoholism history. Sex-related differences in white matter connectivity were observed in association with alcoholism: Compared to nonalcoholic men, alcoholic men had diminished FA in portions of the corpus callosum, the superior longitudinal fasciculi II and III, and the arcuate fasciculus and extreme capsule. In contrast, alcoholic women had higher FA in these regions. Sex differences also were observed for correlations between corpus callosum FA and length of sobriety. Our results suggest that sexual dimorphism in white matter microstructure in abstinent alcoholics may implicate underlying differences in the neurobehavioral liabilities for developing alcohol abuse disorders, or for sequelae following abuse.
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The current study examined whether the steroid hormone, 17β-estradiol (E2) can exert long-lasting beneficial effects upon axonal health, synaptic plasticity, dementia-related amyloid-beta (Aβ) protein expression, and hippocampal-dependent cognitive function in an animal model of chronic cerebral hypoperfusion and vascular dementia (VaD). Chronic cerebral hypoperfusion and VaD was induced by bilateral common carotid artery occlusion (BCCAO) in adult male Sprague Dawley rats. Low dose E2 administered for the first 3-months after BCCAO exerted long-lasting beneficial effects, including significant neuroprotection of hippocampal CA1 neurons and preservation of hippocampal-dependent cognitive function when examined at 6-months after BCCAO. E2 treatment also prevented BCCAO-induced damage to hippocampal myelin sheaths and oligodendrocytes, enhanced expression of the synaptic proteins synaptophysin and PSD95 in the hippocampus, and prevented BCCAO-induced loss of total and mushroom dendritic spines in the hippocampal CA1 region. Furthermore, E2-treatment also reduced BCCAO induction of dementia-related proteins expression such as p-tau (PHF1), total ubiquitin, and Aβ1-42, when examined at 6 m after BCCAO. Taken as a whole, the results suggest that low-dose E2 replacement might be a potentially promising therapeutic modality to attenuate or block negative neurological consequences of chronic cerebral hypoperfusion and VaD.
Alcohol intoxication plays a significant and causal role in various fatal injuries. In comparison to sober individuals, intoxicated people have a greater generic risk for being involved in hazardous activities that may result in fatal injuries. However, it is not clear whether the biological effects of acute alcohol intoxication result in worse injuries than those sustained by sober individuals who are injured by identical mechanisms. Alcohol intoxication has a neuroprotective effect in experimental animal models of traumatic brain injury (TBI) but the evidence for a similar effect in humans is controversial. Earlier studies found such a protective effect, but more recent large epidemiological studies have not confirmed this finding; some studies also suggest a dose-related protective or exacerbating effect of alcohol intoxication on TBI. There are two apparent alcohol-associated syndromes in which an otherwise survivable blunt force impact to the head of an intoxicated individual is fatal at the scene. The first is a fatal cardiorespiratory arrest (the so-called alcohol concussion syndrome or “commotio medullaris”); the second is “traumatic basilar subarachnoid hemorrhage” (secondary to tears in the cerebral arteries, particularly the intracranial and extracranial vertebral arteries).
Aims:
We characterized the metabolite content and axonal fibre changes in the rat pontine, in vivo, using (1)H-magnetic resonance spectroscopy (1H-MRS) and diffusion tensor imaging (DTI) with a 7.0 T magnetic resonance imaging (MRI) scanner following chronic alcohol administration to explore new indicators for the early diagnosis and treatment of chronic alcoholism.
Methods:
Forty male Sprague-Dawley rats were randomly divided into the EtOH and control groups (water group). To establish a chronic alcohol administration rat model, rats were intragastrically administered edible wine (56% vol/vol) twice daily for four weeks. Quantitation of the changes in metabolite concentrations and the apparent diffusion coefficient (ADC), as well as the fractional anisotropy (FA) values, within the pontine of brain stem were detected using MRS and DTI at 7.0 T. Differences of the pontine metabolite content, ADC and FA values between the two groups were compared.
Results:
The 7.0 T MRIs showed no abnormal T2 phase pontine signals in either the EtOH or control groups. A (1)H-MRS scan showed that the values for NAA, Cr and Cho in the EtOH group (4.54 ± 0.69, 4.69 ± 0.70 and 1.32 ± 0.18) were lower than those in the controls (6.78 ± 0.76, 8.50 ± 0.83 and 1.89 ± 0.24) (P < 0.01). However, the Glu+Gln values did not significantly differ between the controls (8.11 ± 1.11) and the EtOH group (7.31 ± 0.85) (P > 0.05). DTI showed that the FA value in chronic alcohol exposure rats (0.41 ± 0.12) was lower than the control rats (0.53 ± 0.08) (P < 0.05). However, the difference in the ADC values was not significant between the controls (0.0014 ± 0.00050) and the EtOH group (0.0012 ± 0.00027) rats (P > 0.05).
Conclusions:
After chronic alcohol exposure for four weeks, the metabolite content and axonal fibre changes in the rat pontine can be detected using MRS and DTI at 7.0 T earlier than conventional MRI, which provides information for the early diagnosis and treatment of chronic alcoholism.
Short summary:
In the present study, the authors showed that the metabolite content and axonal fibre changes in the pontine of chronic ethanol-treated rats can be detected using MRS and DTI at 7.0 T earlier than conventional MRI, which provide objective indicators for the early diagnosis and treatment of chronic alcoholism.
