scholarly journals Brain ischaemia induces shedding of a BDNF-scavenger ectodomain from TrkB receptors by excitotoxicity activation of metalloproteinases and γ-secretases

2016 ◽  
Vol 238 (5) ◽  
pp. 627-640 ◽  
Author(s):  
Gonzalo S Tejeda ◽  
Sara Ayuso-Dolado ◽  
Raquel Arbeteta ◽  
Gema M Esteban-Ortega ◽  
Oscar G Vidaurre ◽  
...  
Keyword(s):  
Brain Ischaemia ◽  
Trkb Receptors

Clinical impact of transoesophageal echocardiography in acute brain ischaemia: who should we select?

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
J Ferreira ◽  
M Fonseca ◽  
C Costa ◽  
JM Farinha ◽  
AF Esteves ◽  
...  
Keyword(s):  
Diagnostic Testing ◽  
Screening Method ◽  
Transoesophageal Echocardiography ◽  
Holter Monitoring ◽  
Clinical Impact ◽  
Superior Cerebellar Artery ◽  
Visual Field Defects ◽  
Brain Ischaemia ◽  
Younger Patients ◽  
Baseline Characteristics

Abstract Funding Acknowledgements Type of funding sources: None. Background Stroke is a prevalent disease and is still the leading cause of death in Portugal. Transoesophageal echocardiography (TOE) is a sensitive test often performed to detect embolic sources. However, since its most common findings such as patent foramen ovale (PFO) and atheroma plaques do not necessarily mandate a change in treatment, there is still debate over its clinical impact in the context of brain ischaemia (BI) and which patients (pts) should be submitted to it.  Purpose To assess the clinical impact of TOE following BI and to identify clinical and diagnostic testing results that could help predict which pts benefit from it. Methods A retrospective study was conducted including all pts submitted to TOE in our hospital after acute BI in 2018 and 2019. Clinical and testing data (brain, vascular and cardiac imaging and 24h-Holter monitoring) was analysed and compared between 2 groups: the pts who had findings in TOE compatible with a source of embolism which resulted in a change in treatment ("relevant TOE" group) vs all other pts who had no such findings or whose findings did not result in change in treatment ("others"). Predictors of relevant TOE were also analysed. Results  Of the 87 pts (mean age of 57 and maximum of 83) included in the study, 51 (59%) had findings compatible with a potential source of embolism in TOE, PFO being the most common (n = 42). In only half of them did these findings result in a change in treatment (the relevant TOE group: n = 25; 29% of the overall population). Age and other baseline characteristics did not significantly differ between groups. Pts with a relevant TOE presented more often with visual-field defects (32% vs 10%, p = 0.020) and were more likely to have visible acute lesions on brain imaging (96% vs 76%, p = 0.032) compared with the others. There was also a borderline significant association between the presence of infarct in the territory of the superior cerebellar artery and a relevant TOE (p = 0.054). On the contrary, the presence of significant lesions in extracranial arteries was negatively associated with a relevant TOE (p = 0.016). Considering the whole population, there were no transthoracic echocardiography (TTE) predictors of a relevant TOE but when analysing only younger patients (age < 50), the presence of any abnormality in TTE became associated with a relevant TOE (OR 8.5, CI 1.1-63.9; p = 0.044). We found no predictors of relevant TOE in 24h-Holter results. Conclusions TOE commonly identified potential sources of brain embolism, which proved relevant in half the cases. In the impossibility of submitting all BI patients to TOE, this study suggests that brain and vascular imaging rather than age or other baseline characteristics may be useful in predicting a relevant result. Moreover, TTE does not seem to be an adequate screening method to select patients for TOE, except possibly in younger patients. Studies with larger samples are needed to confirm these results.

scholarly journals Combined kinesin-1 and kinesin-3 activity drives axonal trafficking of TrkB receptors in Rab6 carriers

2021 ◽  
Vol 56 (10) ◽  
pp. 1552-1554
Author(s):  
Eitan Erez Zahavi ◽  
Jessica J.A. Hummel ◽  
Yuhao Han ◽  
Citlali Bar ◽  
Riccardo Stucchi ◽  
...  
Keyword(s):  
Trkb Receptors ◽  
Axonal Trafficking

scholarly journals Protective effects of carbonic anhydrase inhibition in brain ischaemia in vitro and in vivo models

2021 ◽  
Vol 36 (1) ◽  
pp. 964-976
Author(s):  
Ilaria Dettori ◽  
Irene Fusco ◽  
Irene Bulli ◽  
Lisa Gaviano ◽  
Elisabetta Coppi ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Protective Effects ◽  
Brain Ischaemia ◽  
In Vivo Models ◽  
Carbonic Anhydrase Inhibition

scholarly journals TrkB neurotrophic activities are blocked by α-synuclein, triggering dopaminergic cell death in Parkinson’s disease

2017 ◽  
Vol 114 (40) ◽  
pp. 10773-10778 ◽  
Author(s):  
Seong Su Kang ◽  
Zhentao Zhang ◽  
Xia Liu ◽  
Fredric P. Manfredsson ◽  
Matthew J. Benskey ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuronal Death ◽  
Kinase Domain ◽  
Alpha Synuclein ◽  
Mao B ◽  
Protein Levels ◽  
Trkb Receptors ◽  
Alpha Synuclein Aggregation ◽  
Neurotrophic Signaling

BDNF/TrkB neurotrophic signaling is essential for dopaminergic neuronal survival, and the activities are reduced in the substantial nigra (SN) of Parkinson’s disease (PD). However, whether α-Syn (alpha-synuclein) aggregation, a hallmark in the remaining SN neurons in PD, accounts for the neurotrophic inhibition remains elusive. Here we show that α-Syn selectively interacts with TrkB receptors and inhibits BDNF/TrkB signaling, leading to dopaminergic neuronal death. α-Syn binds to the kinase domain on TrkB, which is negatively regulated by BDNF or Fyn tyrosine kinase. Interestingly, α-Syn represses TrkB lipid raft distribution, decreases its internalization, and reduces its axonal trafficking. Moreover, α-Syn also reduces TrkB protein levels via up-regulation of TrkB ubiquitination. Remarkably, dopamine’s metabolite 3,4-Dihydroxyphenylacetaldehyde (DOPAL) stimulates the interaction between α-Syn and TrkB. Accordingly, MAO-B inhibitor rasagiline disrupts α-Syn/TrkB complex and rescues TrkB neurotrophic signaling, preventing α-Syn–induced dopaminergic neuronal death and restoring motor functions. Hence, our findings demonstrate a noble pathological role of α-Syn in antagonizing neurotrophic signaling, providing a molecular mechanism that accounts for its neurotoxicity in PD.

Distribution of domperidone into the rat brain is increased by brain ischaemia or treatment with the P-glycoprotein inhibitor verapamil

2002 ◽  
Vol 54 (5) ◽  
pp. 729-733 ◽  
Author(s):  
Yukihiko Dan ◽  
Hideyasu Murakami ◽  
Noriko Koyabu ◽  
Hisakazu Ohtani ◽  
Yasufumi Sawada
Keyword(s):  
Rat Brain ◽  
Brain Ischaemia ◽  
P Glycoprotein

Transient brain ischaemia (20 January 1978, p. 6): clarification and correction

1978 ◽  
Vol 16 (23) ◽  
pp. 92-92
Keyword(s):  
Carotid Endarterectomy ◽  
Carotid Stenosis ◽  
Brain Ischaemia

Our statement that in patients with transient brain ischaemia carotid endarterectomy reduces the risk of a subsequent stroke from 28% to 3% (based on the report by Wylie & Ehrenfeld, 1970) should have been qualified. We should have referred also to the study by W. S. Fields et al. (J. Amer. med. Ass. 1970, 211, 1993), in which 4% of the surgically treated patients with unilateral carotid stenosis and 12% of the controls had a stroke during the follow-up period of, on average, 3½ years. These results are based on a small total number of strokes and remain inconclusive. The paper by Whisnant was cited in error. The conclusion of our article is not affected.

BDNF-Induced Facilitation of Afferent-Evoked Responses in Lamina II Neurons Is Reduced After Neonatal Spinal Cord Contusion Injury

2005 ◽  
Vol 94 (3) ◽  
pp. 1798-1804 ◽  
Author(s):  
Sandra M. Garraway ◽  
Aileen J. Anderson ◽  
Lorne M. Mendell
Keyword(s):  
Nmda Receptor ◽  
Dorsal Root ◽  
Dependent Manner ◽  
Evoked Responses ◽  
Patch Clamp Technique ◽  
Synaptic Facilitation ◽  
Trkb Receptors ◽  
Contusion Injury ◽  
Nmda Receptor Function ◽  
Spinal Cord Contusion

We previously reported that brain-derived neurotrophic factor (BDNF), a pronociceptive neurotransmitter, induces synaptic facilitation of excitatory postsynaptic current (EPSC) in lamina II neurons of neonatal rats up to P14 in a N-methyl-d-aspartate (NMDA) receptor-dependent manner. Here we used the patch-clamp technique to study synaptic and NMDA-evoked responses in transverse spinal slices in the lumbar enlargement as well as the ability of BDNF to modify these responses from 1 day to 6 wk after neonatal contusion. In older uninjured animals (>P14), BDNF continued to evoke synaptic facilitation although superfusion of NMDA (in TTX) induced inward current of significantly smaller amplitude than that observed in younger rats. After contusion injury, BDNF was unable to facilitate dorsal root-evoked EPSCs in lamina II neurons despite the finding that NMDA-evoked currents were only slightly smaller than those observed in age-matched uninjured animals. These findings suggest that although BDNF-induced facilitation of the AMPA/kainate receptor-mediated response to dorsal root stimulation is maintained in the mature dorsal horn from intact rats, BDNF may no longer elicit these pronociceptive actions after neonatal contusion injury. The lack of change in NMDA-evoked currents in contused cords suggests that diminished NMDA receptor function is not the major cause of the decline in BDNF action after contusion. It seems more likely that diminished trkB expression and enhanced expression of truncated trkB receptors in the contused cord play a significant role in determining the reduced effect of BDNF under these conditions.

scholarly journals The Role of SUMOylation and Ubiquitination in Brain Ischaemia: Critical Concepts and Clinical Implications

2020 ◽  
pp. 127-144
Author(s):  
Joshua D. Bernstock ◽  
Daniel G. Ye ◽  
Dagoberto Estevez ◽  
Gustavo Chagoya ◽  
Ya-Chao Wang ◽  
...  
Keyword(s):  
Clinical Implications ◽  
Brain Ischaemia
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