Overexpression of the Glucose Transporter Gene with a Herpes Simplex Viral Vector Protects Striatal Neurons against Stroke

Lawrence, Matthew S.; Sun, Guo Hua; Kunis, David M.; Saydam, Tippi C.; Dash, Raj; Ho, Dora Y.; Sapolsky, Robert M.; Steinberg, Gary K.

doi:10.1097/00004647-199603000-00001

Cited by 92 publications

(55 citation statements)

References 23 publications

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“…The left middle cerebral artery (MCA) was occluded by inserting an intraluminal 3-0 nylon monofilament suture through the common carotid artery to the branch point of the MCA. 5 After 1 hour of ischemia, the suture was withdrawn. Normothermic rats were allowed to recover for 3.5 hours and then were reanesthetized.…”

Section: Surgerymentioning

confidence: 99%

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Mild Postischemic Hypothermia Prolongs the Time Window for Gene Therapy by Inhibiting Cytochrome c Release

Zhao

Yenari

Sapolsky

et al. 2004

Stroke

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Background and Purpose-We showed previously that Bcl-2 overexpression with the use of herpes simplex viral (HSV) vectors improved striatal neuron survival when delivered 1.5 hours after stroke but not when delivered 5 hours after stroke onset. Here we determine whether hypothermia prolongs the therapeutic window for gene therapy. Methods-Rats were subjected to focal ischemia for 1 hour. Hypothermia (33°C) was induced 2 hours after insult and maintained for 3 hours. Five hours after ischemia onset, HSV vectors expressing Bcl-2 plus ␤-gal or ␤-gal alone were injected into each striatum. Rats were killed 2 days later. Results-Striatal neuron survival of Bcl-2-treated, hypothermic animals was improved 2-to 3-fold over control-treated, hypothermic animals and Bcl-2-treated, normothermic animals. Neuron survival among normothermic, Bcl-2-treated animals was not different from control normothermics or control hypothermics.

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Section: Surgerymentioning

confidence: 99%

“…We and others have shown that herpes simplex viral (HSV) vectors expressing Bcl-2, 2,3 HSP72, 4 glucose transporter, 5 and calbindin D28K 6 delivered before ischemia reduce neuron death. More clinically relevant is our demonstration that vectors expressing Bcl-2 7 or HSP72 8 also improve striatal neuron survival when delivered up to 2 hours after insult.…”

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confidence: 99%

Mild Postischemic Hypothermia Prolongs the Time Window for Gene Therapy by Inhibiting Cytochrome c Release

Zhao

Yenari

Sapolsky

et al. 2004

Stroke

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“…1,2 Recent studies of gene therapy suggest that gene transfer of cytoprotective proteins, including interleukin-1 receptor antagonist (IL-1ra), glucose transporter, and hsp72, may protect against brain ischemia. [3][4][5] In most of these studies, however, gene transfer was performed before induction of brain ischemia, and the efficacy of postischemic gene therapy for brain infarction is still not established.…”

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confidence: 99%

Postischemic Gene Transfer of Interleukin-10 Protects Against Both Focal and Global Brain Ischemia

et al. 2005

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Background-Gene therapy may be a promising approach for treatment of brain ischemia, although the efficiency of postischemic gene therapy is not established. Our goal in this study was to examine the effects of gene transfer of interleukin-10 (IL-10), an antiinflammatory cytokine, after induction of brain ischemia. Methods and Results-Brain ischemia was produced by either photochemical occlusion of distal middle cerebral artery for focal ischemia or bilateral carotid occlusion for global ischemia in spontaneously hypertensive rats. Adenoviral vectors encoding human IL-10 (AdIL10) or ␤-galactosidase (control) were injected into the lateral ventricle 90 or 60 minutes after focal or global ischemia. Five days after ischemia, IL-10, IL-1␤, or tissue necrosis factor-␣ in the cerebrospinal fluid, infarct volume, infiltrations of leukocytes/macrophages in the infarct area, or hippocampal neuronal damages were determined. The transduced IL-10 was released to the cerebrospinal fluid from the ventricular wall and increased to 7623Ϯ2965 pg/mL 5 days after AdIL10 transfection. Cerebral blood flow during ischemia was not different between treatments in either focal or global ischemia. Brain infarction of the AdIL10 group was significantly smaller and infiltrations of leukocytes and macrophages were fewer in the IL-10 treatment than control. Hippocampal neurons after global ischemia were more preserved, and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling-positive cells were diminished by the IL-10 gene transfer with attenuated IL-1␤ and augmented tissue necrosis factor-␣. Conclusions-Postischemic

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“…Gene therapy is used to alter neuronal physiology and to intervene in the pathological cascade of events that is induced in neurons following various insults. Many steps in the necrotic death pathway have been targeted successfully with viral vectors (derived from HSV or adenovirus) including energetic components (by overexpressing a glucose transporter), [1][2][3][4] the calcium excess (with overexpression of the calcium binding protein, calbindin D 28k ), [5][6][7] the protein malfolding (with hsp72), 8,9 the apoptotic elements (with apoptosis inhibitors such as bcl-2 or NAIP), [10][11][12][13][14] and the inflammatory elements. 15,16 In contrast to these consistent findings, results concern- ing the effects of viral infection itself (independent of the gene delivered) are not clear.…”

Section: Introductionmentioning

confidence: 99%

Delivery of herpes simplex virus amplicon-based vectors to the dentate gyrus does not alter hippocampal synaptic transmission in vivo

Dumas

McLaughlin

et al. 1999

Gene Ther

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Herpes simplex virus type-1 (HSV) amplicon vectors con-(I/O) curves were not altered by infection. Paired-pulse taining neuroprotective genes can alter cell physiology and facilitation at either recording site was also unaffected. Xenhance survival following various insults. However, to gal-positive granule cells surrounded the recording elecdate, little is known about effects of viral infection itself trode (PP-DG recording) and stimulating electrode tracts (independent of the gene delivered) on neuronal physi-(MF-CA3 recording) in animals that received vector, sugology. Electrically-evoked synaptic responses are routinely gesting that we had measured function, at least in part, in recorded to measure functional alterations in the nervous infected neurons. Because of the negative electrophysiolsystem and were used here to assess the potential capaogical result, we sought to deliver a gene with an HSV bility of HSV vectors to disrupt physiology of the hippocamamplicon which would affect the measured endpoints, as pus (a forebrain structure involved in learning that is highly a positive control. Delivery of calbindin D 28k potentiated susceptible to necrotic insult, making it a frequent target in PP-DG synaptic strength, indicating that our recording sysgene therapy research). Population excitatory post-synaptem could detect alterations due to vector expression. tic potentials (EPSPs) were recorded in the dentate gyrus Thus, the data indicate that HSV vectors are benign, in (DG) and in area CA3 in vivo 72 h after infusion of an HSV regard to effects on synaptic function, and support the use vector expressing a reporter gene (lacZ) or vehicle into the of these vectors as a safe method to deliver selected DG. Evoked perforant path (PP-DG) or mossy fiber (MFgenes to the central nervous system. CA3) EPSPs slope values measured across input/output

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Overexpression of the Glucose Transporter Gene with a Herpes Simplex Viral Vector Protects Striatal Neurons against Stroke

Cited by 92 publications

References 23 publications

Mild Postischemic Hypothermia Prolongs the Time Window for Gene Therapy by Inhibiting Cytochrome c Release

Mild Postischemic Hypothermia Prolongs the Time Window for Gene Therapy by Inhibiting Cytochrome c Release

Postischemic Gene Transfer of Interleukin-10 Protects Against Both Focal and Global Brain Ischemia

Delivery of herpes simplex virus amplicon-based vectors to the dentate gyrus does not alter hippocampal synaptic transmission in vivo

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