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The sigma-1 receptor enhances brain plasticity and functional recovery after experimental stroke.

Ruscher, Karsten LU ; Shamloo, Mehrdad; Rickhag, Mattias; Ladunga, Istvan; Soriano, Liza; Gisselsson, Lennart; Toresson, Håkan LU ; Ruslim-Litrus, Lily; Oksenberg, Donna and Urfer, Roman, et al. (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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published
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Brain
volume
134
issue
3
pages
732 - 746
publisher
Oxford University Press
external identifiers
  • wos:000287745100010
  • pmid:21278085
  • scopus:79952126094
ISSN
1460-2156
DOI
10.1093/brain/awq367
language
English
LU publication?
yes
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932f4e95-b31e-48af-95e5-4de74bcc24c9 (old id 1832555)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21278085?dopt=Abstract
date added to LUP
2011-03-01 10:37:22
date last changed
2017-10-22 04:53:46
@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},
  volume       = {134},
  year         = {2011},
}