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Sökning: WFRF:(Nicoletti Ferdinando) > Inhibiting metabotr...

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FältnamnIndikatorerMetadata
00007433naa a2200433 4500
001oai:lup.lub.lu.se:10291d5e-8497-4039-91d0-3c5085fbad3c
003SwePub
008231205s2024 | |||||||||||000 ||eng|
0247 a https://lup.lub.lu.se/record/10291d5e-8497-4039-91d0-3c5085fbad3c2 URI
0247 a https://doi.org/10.1093/brain/awad2932 DOI
040 a (SwePub)lu
041 a engb eng
042 9 SwePub
072 7a art2 swepub-publicationtype
072 7a ref2 swepub-contenttype
1001 a Hakon, Jakobu Lund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine4 aut0 (Swepub:lu)med-jch
2451 0a Inhibiting metabotropic glutamate receptor 5 after stroke restores brain function and connectivity
264 1c 2024
520 a Stroke results in local neural disconnection and brain-wide neuronal network dysfunction leading to neurological deficits. Beyond the hyper-acute phase of ischemic stroke, there is no clinically-approved pharmacological treatment that alleviates sensorimotor impairments. Functional recovery after stroke involves the formation of new or alternative neuronal circuits including existing neural connections. The type-5 metabotropic glutamate receptor (mGluR5) has been shown to modulate brain plasticity and function, and is a therapeutic target in neurological diseases outside of stroke. We investigated whether mGluR5 influences functional recovery and network reorganization rodent models of focal ischemia. Using multiple behavioral tests we observed that treatment with negative allosteric modulators (NAMs) of mGluR5 (MTEP, fenobam, and AFQ056) for 12 days, starting 2 or 10 days after stroke, restored lost sensorimotor functions, without diminishing infarct size. Recovery was evident within hours after initiation of treatment and progressed over the subsequent 12 days. Recovery was prevented by activation of mGluR5 with the positive allosteric modulator VU0360172, and accelerated in mGluR5 KO mice compared to wild-type mice. After stroke, multisensory stimulation by enriched environments (EE) enhanced recovery, a result prevented by VU0360172, implying a role of mGluR5 in EE-mediated recovery. Additionally, MTEP treatment in conjunction with EE housing provided an additive recovery enhancement compared to either MTEP or EE alone. Using optical intrinsic signal imaging, we observed brain-wide disruptions in resting-state functional connectivity after stroke that were prevented by mGluR5 inhibition in distinct areas of contralesional sensorimotor and bilateral visual cortices. The levels of mGluR5 protein in mice and in tissue samples of stroke patients were unchanged after stroke. We conclude that neuronal circuitry subserving sensorimotor function after stroke is depressed by a mGluR5-dependent maladaptive plasticity mechanism that can be restored by mGluR5 inhibition. Post-acute stroke treatment with mGluR5 NAMs combined with rehabilitative training may represent a novel post-acute stroke therapy.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Neurologi0 (SwePub)302072 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Neurology0 (SwePub)302072 hsv//eng
7001 a Quattromani, Miriana Ju Lund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine4 aut0 (Swepub:lu)med-mqu
7001 a Sjölund, Carinu Lund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUBIN Lab- Lunds laboratorium för neurokirurgisk hjärnskadeforskning,Forskargrupper vid Lunds universitet,Laboratory for Experimental Brain Research,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,LUBIN Lab- Lund Brain Injury laboratory for Neurosurgical research,Lund University Research Groups4 aut0 (Swepub:lu)expb-csj
7001 a Talhada, Danielau Lund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine4 aut0 (Swepub:lu)med-det
7001 a Kim, Bungchanu Washington State University4 aut
7001 a Moyanova, Slaviankau Istituto Neurologico Mediterraneo Neuromed4 aut
7001 a Mastroiacovo, Federicau Istituto Neurologico Mediterraneo Neuromed4 aut
7001 a Di Menna, Luisau Istituto Neurologico Mediterraneo Neuromed4 aut
7001 a Olsson, Rogeru Lund University,Lunds universitet,NanoLund: Centre for Nanoscience,Annan verksamhet, LTH,Lunds Tekniska Högskola,Kemisk biologi med inriktning mot läkemedelsutveckling,Forskargrupper vid Lunds universitet,Centrum för analys och syntes,Kemiska institutionen,Institutioner vid LTH,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,LTH profilområde: Nanovetenskap och halvledarteknologi,LTH profilområden,LU profilområde: Ljus och material,Lunds universitets profilområden,Other operations, LTH,Faculty of Engineering, LTH,Chemical Biology and Therapeutics,Lund University Research Groups,Centre for Analysis and Synthesis,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH,LUCC: Lund University Cancer Centre,Other Strong Research Environments,LTH Profile Area: Nanoscience and Semiconductor Technology,LTH Profile areas,Faculty of Engineering, LTH,LU Profile Area: Light and Materials,Lund University Profile areas4 aut0 (Swepub:lu)med-reo
7001 a Englund, Elisabetu Lund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Patologi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Pathology, Lund,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine4 aut0 (Swepub:lu)pat-een
7001 a Nicoletti, Ferdinandou Sapienza University of Rome,Istituto Neurologico Mediterraneo Neuromed4 aut
7001 a Ruscher, Karstenu Lund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUBIN Lab- Lunds laboratorium för neurokirurgisk hjärnskadeforskning,Forskargrupper vid Lunds universitet,Laboratory for Experimental Brain Research,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine,LUBIN Lab- Lund Brain Injury laboratory for Neurosurgical research,Lund University Research Groups4 aut0 (Swepub:lu)med-ktr
7001 a Bauer, Adam Qu Washington State University4 aut
7001 a Wieloch, Tadeuszu Lund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine4 aut0 (Swepub:lu)efor-twi
7102 a Neurokirurgib Sektion IV4 org
7730 t Brain : a journal of neurologyg 147:1, s. 186-200q 147:1<186-200x 1460-2156
8564 u http://dx.doi.org/10.1093/brain/awad293x freey FULLTEXT
8564 8u https://lup.lub.lu.se/record/10291d5e-8497-4039-91d0-3c5085fbad3c
8564 8u https://doi.org/10.1093/brain/awad293

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