The sigma-1 receptor enhances brain plasticity and functional recovery after experimental stroke.
(2011) In Brain 134(3). p.732-746- Abstract
- Stroke leads to brain damage with subsequent slow and incomplete recovery of lost brain functions. Enriched housing of stroke-injured rats provides multi-modal sensorimotor stimulation, which improves recovery, although the specific mechanisms involved have not been identified. In rats housed in an enriched environment for two weeks after permanent middle cerebral artery occlusion, we found increased sigma-1 receptor expression in peri-infarct areas. Treatment of rats subjected to permanent or transient middle cerebral artery occlusion with 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride, an agonist of the sigma-1 receptor, starting two days after injury, enhanced the recovery of lost sensorimotor function without... (More)
- Stroke leads to brain damage with subsequent slow and incomplete recovery of lost brain functions. Enriched housing of stroke-injured rats provides multi-modal sensorimotor stimulation, which improves recovery, although the specific mechanisms involved have not been identified. In rats housed in an enriched environment for two weeks after permanent middle cerebral artery occlusion, we found increased sigma-1 receptor expression in peri-infarct areas. Treatment of rats subjected to permanent or transient middle cerebral artery occlusion with 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride, an agonist of the sigma-1 receptor, starting two days after injury, enhanced the recovery of lost sensorimotor function without decreasing infarct size. The sigma-1 receptor was found in the galactocerebroside enriched membrane microdomains of reactive astrocytes and in neurons. Sigma-1 receptor activation increased the levels of the synaptic protein neurabin and neurexin in membrane rafts in the peri-infarct area, while sigma-1 receptor silencing prevented sigma-1 receptor-mediated neurite outgrowth in primary cortical neuronal cultures. In astrocytic cultures, oxygen and glucose deprivation induced sigma-1 receptor expression and actin dependent membrane raft formation, the latter blocked by sigma-1 receptor small interfering RNA silencing and pharmacological inhibition. We conclude that sigma-1 receptor activation stimulates recovery after stroke by enhancing cellular transport of biomolecules required for brain repair, thereby stimulating brain plasticity. Pharmacological targeting of the sigma-1 receptor provides new opportunities for stroke treatment beyond the therapeutic window of neuroprotection. (Less)
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https://lup.lub.lu.se/record/1832555
- author
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Brain
- volume
- 134
- issue
- 3
- pages
- 732 - 746
- publisher
- Oxford University Press
- external identifiers
-
- wos:000287745100010
- pmid:21278085
- scopus:79952126094
- pmid:21278085
- ISSN
- 1460-2156
- DOI
- 10.1093/brain/awq367
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Laboratory for Experimental Brain Research (013041000), Neurology, Lund (013027000)
- id
- 932f4e95-b31e-48af-95e5-4de74bcc24c9 (old id 1832555)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/21278085?dopt=Abstract
- date added to LUP
- 2016-04-04 08:15:01
- date last changed
- 2022-03-23 02:04:00
@article{932f4e95-b31e-48af-95e5-4de74bcc24c9,
abstract = {{Stroke leads to brain damage with subsequent slow and incomplete recovery of lost brain functions. Enriched housing of stroke-injured rats provides multi-modal sensorimotor stimulation, which improves recovery, although the specific mechanisms involved have not been identified. In rats housed in an enriched environment for two weeks after permanent middle cerebral artery occlusion, we found increased sigma-1 receptor expression in peri-infarct areas. Treatment of rats subjected to permanent or transient middle cerebral artery occlusion with 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride, an agonist of the sigma-1 receptor, starting two days after injury, enhanced the recovery of lost sensorimotor function without decreasing infarct size. The sigma-1 receptor was found in the galactocerebroside enriched membrane microdomains of reactive astrocytes and in neurons. Sigma-1 receptor activation increased the levels of the synaptic protein neurabin and neurexin in membrane rafts in the peri-infarct area, while sigma-1 receptor silencing prevented sigma-1 receptor-mediated neurite outgrowth in primary cortical neuronal cultures. In astrocytic cultures, oxygen and glucose deprivation induced sigma-1 receptor expression and actin dependent membrane raft formation, the latter blocked by sigma-1 receptor small interfering RNA silencing and pharmacological inhibition. We conclude that sigma-1 receptor activation stimulates recovery after stroke by enhancing cellular transport of biomolecules required for brain repair, thereby stimulating brain plasticity. Pharmacological targeting of the sigma-1 receptor provides new opportunities for stroke treatment beyond the therapeutic window of neuroprotection.}},
author = {{Ruscher, Karsten and Shamloo, Mehrdad and Rickhag, Mattias and Ladunga, Istvan and Soriano, Liza and Gisselsson, Lennart and Toresson, Håkan and Ruslim-Litrus, Lily and Oksenberg, Donna and Urfer, Roman and Johansson, Barbro and Nikolich, Karoly and Wieloch, Tadeusz}},
issn = {{1460-2156}},
language = {{eng}},
number = {{3}},
pages = {{732--746}},
publisher = {{Oxford University Press}},
series = {{Brain}},
title = {{The sigma-1 receptor enhances brain plasticity and functional recovery after experimental stroke.}},
url = {{http://dx.doi.org/10.1093/brain/awq367}},
doi = {{10.1093/brain/awq367}},
volume = {{134}},
year = {{2011}},
}