查看更多>>摘要：EGR1 (early growth response protein 1) overexpression aggravates focal ischemic brain injury, but its role in intracerebral hemorrhage (ICH) induced cerebral injury remains obscure. In this study, a rat ICH model was established by injecting type VII collagenase into the brain, and EGR1 knockdown reversed the increase of hematoma area, neurological function score, brain water content, blood-brain barrier (BBB) permeability, inflammation, p300 and retinoid a X receptor-a (RXRa) protein levels, as well as RXRa acetylation level induced by ICH. EGR1 expression was up-regulated in primary brain microvascular endothelial cells (BMECs), neurons, and astrocytes after ICH induction, and the up-regulation was most significant in BMECs. We also found that EGR1 promoted RXRa acetylation level by regulating p300 in BMECs. Silencing EGR1 rescued the upregulation of cell inflammation and the reduction of cell viability and TEER (transendothelial electric resistance) caused by OGD (oxygen glucose deprivation) plus hemin via p300-mediated RXRa acetylation. Furthermore, the STAT3/ NF-jB pathway was activated after treatment with OGD plus hemin, which was suppressed by silencing EGR1. Treatment with Stattic (an inhibitor of STAT3) restrained the effect of OGD plus hemin on NF-jB pathway activity, inflammation, cell viability and TEER. In conclusion, EGR1 increased RXRa acetylation level by regulating p300, thereby aggravating brain damage in ICH rat model and dysfunction in BMECs, through the STAT3/NF-jB pathway. (c) 2021 IBRO. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：is an iron-dependent form of regulated cell death, which is driven by loss of activity of the lipid repair enzyme glutathione peroxidase 4 (GPX4) and subsequent accumulation of lipid peroxidation. Ferroptosis is implicated in various diseases involving neuronal injury. However, the role of ferroptosis in hypoxic-ischemic brain damage (HIBD) has not been elucidated. The objectives of this study were to evaluate whether ferroptosis is involved in hypoxic-ischemic brain damage and its mechanisms through the HIBD model. A 7-day-old male Sprague-Dawley neonatal rat HIBD model was established by blocking the left common carotid artery. Laser speckle contrast imaging, immunohistochemical staining, transmission electron microscopy were used to measure the effects of ferroptosis on HIBD. Brain tissue on the damaged side in the HIBD group showed atrophied, even liquefied, glial cells increased, and blood perfusion was significantly reduced. The HIBD group insult significantly increased reactive oxygen species levels, as well as the protein levels of iron metabolismrelated proteins transferrin receptor (TFRC), ferritin heavy chain (FHC), and ferritin light chain (FLC), while reducing the levels of Solute Carrier Family 7 Member 11 (SLC7A11), glutathione (GSH), and GPX4. These changes resulted in diminished cellular antioxidant capacity and mitochondrial damage, causing neuronal ferroptosis in the cerebral cortex. We conclude that ferroptosis plays a role in HIBD in neonatal rats. Ferroptosis-related mechanisms such as abnormalities in iron metabolism, amino acid metabolism, and lipid peroxidation regulation play important roles in HIBD. (c) 2022 The Author(s). Published by Elsevier Ltd on behalf of IBRO. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Mao, Cui PingWilson, GeorgiaCao, JinMeshberg, Nathaniel...
12页
查看更多>>摘要：dysfunction is thought to underlie the pathophysiology of chronic pain revealed by electroencephalographic studies. The thalamus serves as a primary relay center to transmit sensory information and motor impulses via dense connections with the somatosensory and motor cortex. In this study, diffusion tensor imaging (DTI) (probabilistic tractography) and resting-state functional magnetic resonance imaging (functional connectivity) were used to characterize the anatomical and functional integrity of the thalamosensorimotor pathway in chronic low back pain (cLBP). Fifty-four patients with cLBP and 54 healthy controls were included. The results suggested significantly increased anatomical connectivity of the left thalamo-motor pathway characterized by probabilistic tractography in patients with cLBP. Moreover, there was significantly altered resting-state functional connectivity (rsFC) of bilateral thalamo-motor/somatosensory pathways in patients with cLBP as compared to healthy controls. We also detected a significant correlation between pain intensity during the MRI scan and rsFC of the right thalamo-somatosensory pathway in cLBP. Our findings highlight the involvement of the thalamo-sensorimotor circuit in the pathophysiology of cLBP. (c) 2022 IBRO. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：hippocampus proper and the subiculum contain two major populations of somatostatin (SST)-containing interneurons, oriens-lacunosum moleculare (O-LM) cells projecting from the stratum oriens to the stratum lacunosum moleculare and bistratified cells with their cell bodies close to the pyramidal cell layer and axons terminating in the strata radiatum and oriens. Both types of interneurons innervate pyramidal cell dendrites and exert prominent feedback inhibition. We now investigated whether impairing this type of feed-back inhibition by selectively inhibiting GABA release from SST expressing interneurons in hippocampal sector CA1 and subicu-lum may be sufficient to induce spontaneous recurrent seizures. We injected transgenic mice expressing Cre-recombinase on the SST promoter unilaterally into the ventral CA1 sector and subiculum with an adeno-associated viral (AAV) vector expressing tetanus toxin light chain (TeLC) with its reading frame inverted in a flip-excision (FLEX) cassette. This treatment resulted in specific expression of TeLC and silencing of SST-containing interneurons. We continuously monitored the EEG and behavior of the mice for six weeks. Nine out of eleven mice within 10 days developed series of pre-or interictal spikes (IS, 21.4 +/- 6.83 per week) and four mice exposed recurrent spontaneous seizures (SRS, 1.5 +/- 0.29 per week). All 23 SRS observed were preceded by IS series. Our data demonstrate a critical role of feed-forward inhibition mediated by SST-containing interneurons suggesting that their sustained malfunctioning can be causatively involved in the development of TLE. (c) 2022 The Authors. Published by Elsevier Ltd on behalf of IBRO. This is an open access article under the CC BY license (http://creati-vecommons.org/licenses/by/4.0/).
查看更多>>摘要：Munc13 family of proteins is critically involved in synaptic vesicle priming and release in glutamatergic neurons in the brain. Munc13-1 binds to alcohol and, in Drosophila, modulates sedation sensitivity and self-administration. We examined the effect of alcohol consumption on the expression of Munc13-1 and Munc13-2, NMDA receptor subunits GluN1, GluN2A and GluN2B in the hippocampus-derived HT22 cells, hippocampal primary neuron culture, and wild-type and Munc13-1+/- male mouse hippocampus after ethanol consumption (Drinking in the Dark (DID) paradigm). In HT22 cells, Munc13-1 was upregulated following 25 mM ethanol treatment for 24 h. In the primary neuronal culture, however, the expression of both Munc13-1 and Munc13-2 increased after ethanol exposure. While Munc13-1 was upregulated in the hippocampus, Munc13-2 was downregulated following DID. This differential effect was found in the CA1 subfield of the hippocampus. Although Munc13-1+/- mice had approximately 50% Munc13-1 expression compared to wild-type, it was nonetheless significantly increased following DID. Munc13-1 and Munc13-2 were expressed in vesicular glutamate transporter1 (VGLUT1) immunoreactive neurons in the hippocampus, but ethanol did not alter the expression of VGLUT1. The NMDA receptor subunits, GluN1, GluN2A and GluN2B were upregulated in the hippocampal primary culture and in the CA1. Ethanol exerts a differential effect on the expression of Munc13-1 and Munc13-2 in the CA1 in male mice. Our study also found that ethanol's effect on Munc13 expression is dependent on the experimental paradigm, and both Munc13-1 and Munc13-2 could contribute to the ethanol-induced augmentation of glutamatergic neurotransmission. (c) 2022 IBRO. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：growing number of functional neuroimaging studies have identified regions within the temporal lobe, particularly along the planum polare and planum temporale, that respond more strongly to music than other types of acoustic stimuli, including voice. This "music preferred" regions have been reported using a variety of stimulus sets, paradigms and analysis approaches and their consistency across studies confirmed through metaanalyses. However, the critical question of intra-subject reliability of these responses has received less attention. Here, we directly assessed this important issue by contrasting brain responses to musical vs. vocal stimuli in the same subjects across three consecutive fMRI runs, using different types of stimuli. Moreover, we investigated whether these music- and voice-preferred responses were reliably modulated by expertise. Results demonstrated that music-preferred activity previously reported in temporal regions, and its modulation by expertise, exhibits a high intra-subject reliability. However, we also found that activity in some extra-temporal regions, such as the precentral and middle frontal gyri, did depend on the particular stimuli employed, which may explain why these are less consistently reported in the literature. Taken together, our findings confirm and extend the notion that specific regions in the brain consistently respond more strongly to certain socially-relevant stimulus categories, such as faces, voices and music, but that some of these responses appear to depend, at least to some extent, on the specific features of the paradigm employed. (c) 2022 IBRO. Published by Elsevier Ltd. All rights reserved.
查看更多>>摘要：Previous studies have reported altered neuroimaging features in right temporal lobe epilepsy (rTLE). However, the alterations in degree centrality (DC) as a diagnostic method for rTLE have not been reported. There-fore, we aimed to explore abnormalities in the DC of the rTLE and whether such alterations could be applied to the diagnosis of rTLE. Resting-state functional magnetic resonance imaging (fMRI) was used to scan 82 patients with rTLE and 69 healthy controls. The DC and support vector machine (SVM) methods were used for an analysis of the imaging data. Compared to the control group, the rTLE patients exhibited lower DC values in the right hippocam-pus, right superior temporal gyrus, and right caudate. Compared to the control group, the rTLE patients showed higher DC values in the right medial superior frontal gyrus (SFGmed), left dorsolateral superior frontal gyrus (SFGdor), right inferior parietal lobule (IPL), and the left postcentral. The highest diagnostic accuracy of 99.34% (150/151), based on SVM analysis, was demonstrated for the combination of abnormal DC in the right IPL and the left SFGdor, along with a sensitivity of 100% (82/82), and a specificity of 98.55% (68/69) for the differ-entiation of rTLE patients from healthy controls. The study demonstrated abnormal functional connectivity in rTLE patients. Thus, a distinctive DC pattern may serve as an imaging marker for the diagnosis of rTLE patients. (c) 2022 IBRO. Published by Elsevier Ltd. All rights reserved.
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