Gene Transfer of Hepatocyte Growth Factor to Subarachnoid Space in Cerebral Hypoperfusion Model

Yoshimura, Shinichi; Morishita, Ryuichi; Hayashi, Kozaburo; Kokuzawa, Jouji; Aoki, Motokuni; Matsumoto, Kunio; Nakamura, Toshikazu; Ogihara, Toshio; Sakai, Noboru; Kaneda, Yasufumi

doi:10.1161/01.hyp.0000017553.67732.e1

Cited by 45 publications

(36 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…16,33 Another possible mechanism for the reduction of the infarct area might be the development of collateral circulation. An angiogenic effect of HGF was reported in a rat cerebral hypoperfusion model 34 and rat transient focal cerebral ischemia model, 9 in addition to the present study. Because the prevention of cerebral infarction was observed at 24 hours after transfection, the neuroprotective action of HGF might be contributed largely to the present results.…”

Section: Discussionsupporting

confidence: 76%

Novel Therapeutic Strategy to Treat Brain Ischemia

et al. 2004

Self Cite

View full text Add to dashboard Cite

Background-Although cerebral occlusive disease leads to cerebral ischemic events, an effective treatment has not yet been established. An ideal therapeutic approach to treat ischemia might have both aspects of enhancement of collateral formation and prevention of neuronal death. Hepatocyte growth factor (HGF) is a potent angiogenic factor that also acts as a neurotrophic factor. Thus, in this study, we examined the therapeutic effects of HGF on brain injury in a rat permanent middle cerebral artery occlusion model. Methods and Results-Gene transfer into the brain was performed by injection of human HGF gene with hemagglutinating virus of Japan-envelope vector into the cerebrospinal fluid via the cisterna magna. Overexpression of the HGF gene resulted in a significant decrease in the infarcted brain area as assessed by triphenyltetrazolium chloride staining, whereas rats transfected with control vector exhibited a wide area of brain death after 24 hours of ischemia. Consistently, the decrease in neurological deficit was significantly attenuated in rats transfected with the HGF gene at 24 hours after the ischemic event. Stimulation of angiogenesis was also detected in rats transfected with the HGF gene compared with controls. Of importance, no cerebral edema or destruction of the blood-brain barrier was observed in rats transfected with the HGF gene. Conclusions-Overall, the present study demonstrated that overexpression of the HGF gene attenuated brain ischemic injury in a rat model, without cerebral edema, through angiogenic and neuroprotective actions. In particular, the reduction of brain injury by HGF may provide a new therapeutic option to treat cerebrovascular disease.

show abstract

Section: Discussionsupporting

confidence: 76%

Novel Therapeutic Strategy to Treat Brain Ischemia

et al. 2004

Self Cite

View full text Add to dashboard Cite

show abstract

“…HGF signaling through the Met receptor induces normal tissue repair in a manner that restores tissue structure and prevents the development of extensive scar formation or fibrosis in liver, kidney, heart, brain, and lung (27,40,41,46,59,66,67). The importance of HGF in tissue repair and the cost and difficulty associated with producing recombinant, active HGF protein has prompted researchers to seek alternative means to activate the pathway, such as inducing endogenous HGF gene expression and protein production using natural and synthetic compounds (45,51,60) or using exogenous expression methods.…”

Section: Discussionmentioning

confidence: 99%

“…However, HGF has been shown to be an important factor in the progression of tumorigenesis, discouraging the treatment of human patients with HGF in retroviral systems that would induce its permanent or constitutive expression. Instead, transient, nonviral in vivo gene transfer techniques have been investigated and demonstrated to be effective in a variety of animal models of organ fibrosis (11,19,51,56,65,67). These methods are currently being tested in early clinical trials for HGF exogenous expression (42).…”

Section: Discussionmentioning

confidence: 99%

A tandem repeat of a fragment of Listeria monocytogenes internalin B protein induces cell survival and proliferation

Mungunsukh

Lee

Marquez

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

-Hepatocyte growth factor (HGF) is critical for tissue homeostasis and repair in many organs including the lung, heart, kidney, liver, nervous system, and skin. HGF is a heterodimeric protein containing 20 disulfide bonds distributed among an amino-terminal hairpin, four kringle domains, and a serine protease-like domain. Due to its complex structure, recombinant production of HGF in prokaryotes requires denaturation and refolding, processes that are impractical for large-scale manufacture. Thus, pharmaceutical quantities of HGF are not available despite its potential applications. A fragment of the Listeria monocytogenes internalin B protein from amino acids 36 -321 (InlB 36 -321) was demonstrated to bind to and partially activate the HGF receptor Met. InlB 36 -321 has a stable ␤-sheet structure and is easily produced in its native conformation by Escherichia coli. We cloned InlB 36 -321 (1ϫInlB36-321) and engineered a head-to-tail repeat of InlB 36 -321 with a linker peptide (2ϫInlB36-321); 1ϫInlB36-321 and 2ϫInlB 36 -321 were purified from E. coli. Both 1ϫ and 2ϫInlB36-321 activated the Met tyrosine kinase. We subsequently compared signal transduction of the two proteins in primary lung endothelial cells. 2ϫInlB 36 -321 activated ERK1/2, STAT3, and phosphatidylinositol 3-kinase/Akt pathways, whereas 1ϫInlB 36 -321 activated only STAT3 and ERK1/2. The 2ϫInlB 36 -321 promoted improved motility compared with 1ϫInlB 36 -321 and additionally stimulated proliferation equivalent to full-length HGF. Both the 1ϫ and 2ϫInlB 36 -321 prevented apoptosis by the profibrotic peptide angiotensin II in cell culture and ex vivo lung slice cultures.

show abstract

“…Although it was previously reported that liposome uptake by capillary endothelial cells is nearly absent in the brain (McLean et al, 1997), the typical liposome injection study does not measure CBF (Mamot et al, 2003;Takada et al, 1982). Previous studies (Yoshimura et al, 2002) demonstrated a CBF increase following liposome infusion; however, the method used for measurement (laser Doppler flow with a probe) can measure only a very small volume (1.5 mm 3 ). Our method (REG) measures a much greater volume, the approximate volume of the entire brain.…”

Section: Discussionmentioning

confidence: 99%

“…Measurement of local CBF does not necessarily reflect CBF autoregulation (Bodo et al, 2004). Additionally, the Yoshimura study (Yoshimura et al, 2002) found that an increase in CBF may be a result of an unknown interaction with the infused materials (see CBF autoregulation discussion next). Liposome infusion requires further study to understand background clinical problems, such as brain blood barrier alteration (Johansson, 1992).…”

Section: Discussionmentioning

confidence: 99%

Cerebrovascular Involvement in Liposome—Induced Cardiopulmonary Distress in Pigs

Bodó

Szebeni

Baranyi

et al. 2005

Journal of Liposome Research

View full text Add to dashboard Cite

The public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing the burden, 14. ABSTRACT Intravenous administration of liposomes, including Doxil, can cause severe life threatening hemodynamic changes in pigs. The reaction is due to complement activation, and it is characterized by massive pulmonary hypertension, systemic hypotension and severe cardiac abnormalities including falling cardiac output, tachy-or bradycardia with arrhythmia. There were no data suggesting the involvement of cerebrovascular changes in this reaction, however clinical observations allowed this hypothesis. Here we measured the accompanying changes during liposome infusion by monitoring pulsatile electrical impedance (rheoencephalogram -REG) on the skull (n = 24 pigs, 57 trials, 19 types of liposomes). A transient but significant decrease of REG pulse amplitudes followed the injection of liposomes (78.43 % in the total sample, and 91.66 % in the Doxil subgroup; P = 0.003, n = 12), indicating the involvement of cerebrovascular reaction during liposome infusion.

show abstract

Gene Transfer of Hepatocyte Growth Factor to Subarachnoid Space in Cerebral Hypoperfusion Model

Cited by 45 publications

References 42 publications

Novel Therapeutic Strategy to Treat Brain Ischemia

Novel Therapeutic Strategy to Treat Brain Ischemia

A tandem repeat of a fragment of Listeria monocytogenes internalin B protein induces cell survival and proliferation

Cerebrovascular Involvement in Liposome—Induced Cardiopulmonary Distress in Pigs

Contact Info

Product

Resources

About