title: Gene transfer of HSP72 protects cornu ammonis 1 region of the hippocampus neurons from global ischemia: influence of Bcl-2.
abstract: We investigated whether HSV gene transfer of HSP72 in vivo and in vitro: (1) protected cornu ammonis 1 region of the hippocampus neurons from global cerebral ischemia; and (2) affected Bcl-2 expression. HSV vectors expressing HSP72 and beta-galactosidase (reporter) or beta-galactosidase only (control vector) were injected into cornu ammonis 1 region of the hippocampus 15 hours before induction of global cerebral ischemia (n = 10) and sham-operated rats (n = 8). HSP72 vector-treated rats displayed significantly more surviving transfected neurons (X-gal-positive, 31 +/- 8) compared with control vector-treated rats (10 +/- 4) after global cerebral ischemia. Sham-operated rats displayed similar numbers of X-gal-positive neurons (HSP72 vector 18 +/- 8 vs control vector 20 +/- 7). The percentage of beta-galactosidase and Bcl-2 coexpressing neurons in HSP72-treated rats after global cerebral ischemia (84 +/- 4%) was greater than that in control vector-treated rats (58 +/- 9%). The percentage of beta-galactosidase and Bcl-2 coexpressing neurons in sham-operated rats was similar in HSP72 (93 +/- 7%) and in control vector-treated rats (88 +/- 12%). HSP72 vector transfection led to 12 times as much Bcl-2 expression as the control vector in uninjured hippocampal neuronal cultures. In injured (oxygen-glucose deprivation) hippocampal neuron cultures, HSP72 vector transfection led to 2.8 times as much Bcl-2 expression as control vector. We show that HSP72 overexpression protects cornu ammonis 1 region of the hippocampus neurons from global cerebral ischemia, and that this protection may be mediated in part by increased Bcl-2 expression.
authors.affiliation: Department of Neurosurgery, Stanford University, Stanford, CA 94305-5327, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Kelly
authors.forename: Zhijian J
authors.initials: ZJ
authors.lastname: Zhang
authors.forename: Heng
authors.initials: H
authors.lastname: Zhao
authors.forename: Lijun
authors.initials: L
authors.lastname: Xu
authors.forename: Rona G
authors.initials: RG
authors.lastname: Giffard
authors.forename: Robert M
authors.initials: RM
authors.lastname: Sapolsky
authors.forename: Midori A
authors.initials: MA
authors.lastname: Yenari
authors.forename: Gary K
authors.initials: GK
authors.lastname: Steinberg
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D015870:Gene Expression; D018014:Gene Transfer Techniques; D019254:Genes, bcl-2; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000378:metabolism / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D001616:beta-Galactosidase