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Gene transfer of HSP72 protects cornu ammonis 1 region of the hippocampus neurons from global ischemia: Influence of Bcl‐2
Author(s) -
Kelly Stephen,
Zhang Zhijian J.,
Zhao Heng,
Xu Lijun,
Giffard Rona G.,
Sapolsky Robert M.,
Yenari Midori A.,
Steinberg Gary K.
Publication year - 2002
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.10264
Subject(s) - hippocampal formation , transfection , ischemia , hippocampus , biology , viral vector , vector (molecular biology) , in vivo , expression vector , medicine , endocrinology , neuroscience , gene , recombinant dna , biochemistry , genetics
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 β‐galactosidase (reporter) or β‐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 β‐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 β‐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.