Gene transfer of HSP72 protects cornu ammonis 1 region of the hippocampus neurons from global ischemia: Influence of Bcl-2

• Published in: Annals of neurology Vol. 52; no. 2; pp. 160 - 167
• Main Authors: Kelly, Stephen, Zhang, Zhijian J., Zhao, Heng, Xu, Lijun, Giffard, Rona G., Sapolsky, Robert M., Yenari, Midori A., Steinberg, Gary K.
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 01.08.2002; Willey-Liss
• Subjects: Animals; beta-Galactosidase - genetics; Biological and medical sciences; Blotting, Western; Brain Ischemia - drug therapy; Brain Ischemia - pathology; Gene Expression; Gene Transfer Techniques; Genes, bcl-2; Heat-Shock Proteins - genetics; Heat-Shock Proteins - metabolism; Heat-Shock Proteins - therapeutic use; Hippocampus - drug effects; Hippocampus - pathology; HSP72 Heat-Shock Proteins; Male; Medical sciences; Neurology; Neuroprotective Agents - metabolism; Neuroprotective Agents - therapeutic use; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rats; Rats, Sprague-Dawley; Vascular diseases and vascular malformations of the nervous system; Animal model; Nervous system diseases; Rat; Herpesviridae; Rodentia; Cardiovascular disease; Neuroprotective agent; Cerebral disorder; Vascular disease; Virus; Vertebrata; Mammalia; Treatment; Ischemia; Animal; Central nervous system disease; Heat shock protein; Immunoblotting assay; Gene therapy; Cerebrovascular disease; Hippocampus; Brain (vertebrata)
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/ana.10264

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.