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Doeppner, Thorsten R.; Doehring, Maria; Kaltwasser, Britta; Majid, Arshad; Lin, Fengyan; Bahr, Mathias; Kilic, Ertugrul; Hermann, Dirk M.
{ "DOI": "10.1007/s12035-016-0137-3", "abstract": "In view of the failure of pharmacological therapies, alternative strategies promoting post-stroke brain repair are needed. Post-conditioning is a potentially promising therapeutic strategy, which induces acute neuroprotection against ischemic injury. To elucidate longer lasting actions of ischemic post-conditioning, mice were exposed to a 60-min stroke and post-conditioning by an additional 10-min stroke that was induced 10 min after reperfusion onset. Animals were sacrificed 24 h or 28 days post-stroke. Post-conditioning reduced infarct volume and neurological deficits 24 h poststroke, enhancing blood-brain barrier integrity, reducing brain leukocyte infiltration, and reducing oxidative stress. On the molecular level, post-conditioning yielded increased Hsp70 expression, whereas nuclear factor (NF)-kappa B and proteasome activities were decreased. Reduced infarct volume and proteasome inhibition were reversed by Hsp70 knockdown, suggesting a critical role of the Hsp70 proteasome pathway in ischemic post-conditioning. The survival-promoting effects of ischemic post-conditioning, however, were not sustainable as neuroprotection and neurological recovery were lost 28 days post-stroke. Although angioneurogenesis was not increased by post-conditioning, the favorable extracellular milieu facilitated intracerebral transplantation of neural progenitor cells 6 h post-stroke, resulting in persisted neuroprotection and neurological recovery. Thus, post-conditioning might support brain repair processes, but in view of its transient, neuroprotection is unlikely useful as stroke therapy in its current form.", "author": [ { "family": "Doeppner", "given": " Thorsten R." }, { "family": "Doehring", "given": " Maria" }, { "family": "Kaltwasser", "given": " Britta" }, { "family": "Majid", "given": " Arshad" }, { "family": "Lin", "given": " Fengyan" }, { "family": "Bahr", "given": " Mathias" }, { "family": "Kilic", "given": " Ertugrul" }, { "family": "Hermann", "given": " Dirk M." } ], "container_title": "MOLECULAR NEUROBIOLOGY", "id": "51479", "issue": "8", "issued": { "date-parts": [ [ 2017, 1, 1 ] ] }, "page": "6061-6073", "title": "Ischemic Post-Conditioning Induces Post-Stroke Neuroprotection via Hsp70-Mediated Proteasome Inhibition and Facilitates Neural Progenitor Cell Transplantation", "type": "article-journal", "volume": "54" }
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