title: A novel immune-based therapy for stroke induces neuroprotection and supports neurogenesis.
abstract: The ability of the central nervous system to cope with stressful conditions was shown to be dependent on proper T-cell-mediated immune response. Because the therapeutic window for neuroprotection after acute insults such as stroke is relatively narrow, we searched for a procedure that would allow the relevant T cells to be recruited rapidly. Permanent middle cerebral artery occlusion was induced in adult rats. To facilitate a rapid poststroke T cell activity, rats were treated with poly-YE using different regimens. Control and poly-YE-treated rats were assessed for functional recovery using neurological severity score and Morris water maze. Neuroprotection, neurogenesis, growth factor expression, and microglial phenotype were assessed using histological and immunofluorescence methods. Administration of poly-YE as late as 24 hours after middle cerebral artery occlusion yielded a beneficial effect manifested by better neurological performance, reduced neuronal loss, attenuation of behavioral deficits, and increased hippocampal and cortical neurogenesis. This compound affected the subacute phase by modulating microglial response and by increasing local production of insulin-like growth factor-I, known to be a key player in neuronal survival and neurogenesis. The relative wide therapeutic window, coupled with its efficacy in attenuating further degeneration and enhancing restoration, makes poly-YE a promising immune-based candidate for stroke therapy.
authors.affiliation: Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yaniv
authors.initials: Y
authors.lastname: Ziv
authors.forename: Arseny
authors.initials: A
authors.lastname: Finkelstein
authors.forename: Yona
authors.initials: Y
authors.lastname: Geffen
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kipnis
authors.forename: Igor
authors.initials: I
authors.lastname: Smirnov
authors.forename: Suzi
authors.initials: S
authors.lastname: Shpilman
authors.forename: Irena
authors.initials: I
authors.lastname: Vertkin
authors.forename: Michal
authors.initials: M
authors.lastname: Kimron
authors.forename: Aya
authors.initials: A
authors.lastname: Lange
authors.forename: Torsten
authors.initials: T
authors.lastname: Hecht
authors.forename: Klaus G
authors.initials: KG
authors.lastname: Reyman
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Marder
authors.forename: Michal
authors.initials: M
authors.lastname: Schwartz
authors.forename: Eti
authors.initials: E
authors.lastname: Yoles
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*
chemical_list: D018696:Neuroprotective Agents