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[EN] Repair of central nervous system (CNS) lesions is difficulted by the lack of ability of central axons to regrow, and the blocking by the brain astrocytes to axonal entry. We hypothesized that by using bridges made of porous biomaterial and permissive olfactory ensheathing glia (OEG), we could provide a scaffold to permit restoration of white matter tracts. We implanted porous polycaprolactone (PCL) bridges between the substantia nigra and the striatum in rats, both with and without OEG. We compared the number of tyrosine-hydroxylase positive (TH+) fibers crossing the striatal-graft interface, and the astrocytic and microglial reaction around the grafts, between animals grafted with and without OEG. Although TH+ fibers were found inside the grafts made of PCL alone, there was a greater fiber density inside the graft and at the striatal-graft interface when OEG was cografted. Also, there was less astrocytic and microglial reaction in those animals. These results show that these PCL grafts are able to promote axonal growth along the nigrostriatal pathway, and that cografting of OEG markedly enhances axonal entry inside the grafts, growth within them, and re-entry of axons into the CNS. These results may have implications in the treatment of diseases such as Parkinson's and others associated with lesions of central white matter tracts. ; Contract grant sponsor: Regional Government Health Department (Conselleria de Sanitat, Generalitat Valenciana) and Carlos III Health Institute of the Ministry of Health and Consumer Affairs (Spain) (Regenerative Medicine Programme) Contract grant sponsor: Spanish ministry of Education and Science; contract grant number: MAT 2006-13554-C02-02 Contract grant sponsor: Red de Terapia Celular TERCEL (RETICS), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovacion (ISCIII); contract grant number: RD12/0019/0010 (to J.A.) Contract grant sponsor: Spanish Science & Innovation Ministery; contract grant number: MAT2008-06434 (to M.M.P.) Contract grant sponsor: "Convenio de ...

Background: Obsessive-compulsive disorder (OCD) has consistently been linked to abnormal frontostriatal activity. The electrophysiological disruption in this circuit, however, remains to be characterized. Objective/hypothesis: The primary goal of this study was to investigate the neuronal synchronization in OCD patients. We predicted aberrant oscillatory activity in frontal regions compared to healthy control subjects, which would be alleviated by deep brain stimulation (DBS) of the nucleus accumbens (NAc). Methods: We compared scalp EEG recordings from nine patients with OCD treated with NAc-DBS with recordings from healthy controls, matched for age and gender. Within the patient group, EEG activity was compared with DBS turned off vs. stimulation at typical clinical settings (3.5 V, frequency of stimulation 130 Hz, pulse width 60 ms). In addition, intracranial EEG was recorded directly from depth macro electrodes in the NAc in four OCD patients. Results: Cross-frequency coupling between the phase of alpha/low beta oscillations and amplitude of high gamma was significantly increased over midline frontal and parietal electrodes in patients when stimulation was turned off, compared to controls. Critically, in patients, beta (16-25 Hz)-gamma (110-166 Hz) phase amplitude coupling source localized to the ventromedial prefrontal cortex, and was reduced when NAc-DBS was active. In contrast, intracranial EEG recordings showed no beta-gamma phase amplitude coupling. The contribution of non-sinusoidal beta waveforms to this coupling are reported. Conclusion: We reveal an increased beta-gamma phase amplitude coupling in fronto-central scalp sensors in patients suffering from OCD, compared to healthy controls, which may derive from ventromedial prefrontal regions implicated in OCD and is normalized by DBS of the nucleus accumbens. This aberrant cross-frequency coupling could represent a biomarker of OCD, as well as a target for novel therapeutic approaches. (C) 2021 The Authors. Published by Elsevier Inc. ; This work was supported by Project grants SAF2015-65982-R from the Spanish Ministry of Economy and Competitiveness to BS and PSI2014-58654-JIN to JGR, an FPI Predoctoral Fellowship (BES-2016-079470) to ST, and BIAL Foundation Grant 119/12 to BS. This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (ERC-2018-COG 819814).