Reply to the Editor

Abstract

My colleagues and I thank Dr Sakurai for his insightful comments on our recently published article. Tolerance induced by gene transfer of hepatocyte growth factor (HGF) against ischemia insults has been well described in the literature, including our study,1Shimamura M. Sato N. Oshima K. Aoki M. Kurinami H. Waguri S. et al.Novel therapeutic strategy to treat brain ischemia: overexpression of hepatocyte growth factor gene reduced ischemic injury without cerebral edema in rat model.Circulation. 2004; 109: 424-431Crossref PubMed Scopus (110) Google Scholar, 2Shi E. Jiang X. Kazui T. Washiyama N. Yamashita K. Terada H. et al.Nonviral gene transfer of hepatocyte growth factor attenuates neurologic injury after spinal cord ischemia in rabbits.J Thorac Cardiovasc Surg. 2006; 132: 941-947Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar in which the question about which cell was the target for gene transfer and then expressed with HGF was eclipsed by the emphasis on the assessment of neuroprotective effects and its possible mechanisms. We appreciate that the question raised by Dr Sakurai is very important. Human HGF was detected in the pia matter and parenchyma when HGF was transferred by intracisternal injection using the same vector. It seemed that multiple cells might secrete HGF, including neurons.3Shimamura M. Sato N. Waguri S. Uchiyama Y. Hayashi T. Iida H. et al.Gene transfer of hepatocyte growth factor gene improves learning and memory in the chronic stage of cerebral infarction.Hypertension. 2006; 47: 742-751Crossref PubMed Scopus (54) Google Scholar Of cause, only further study is the best answer. Spinal cord ischemia can induce two kinds of motor neuron death: necrosis and apoptosis. It is thought that the delayed and selective motor neuron death, which occurs a few days after a relatively short period of spinal cord ischemia (less than 20 minutes in the rabbit model) accompanied by delayed paraplegia, is due to neuronal apoptosis, whereas necrosis usually occurs after acute ischemia.4Sakurai M. Nagata T. Abe K. Horinouchi T. Itoyama Y. Tabayashi K. Survival and death-promoting events after transient spinal cord ischemia in rabbits: induction of Akt and caspase3 in motor neurons.J Thorac Cardiovasc Surg. 2003; 125: 370-377Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar In the current study, rabbits were subjected to a 30-minute period of ischemia, and most animals were completely paraplegic 1 day after transient ischemia. The previous work of our department showed that a 30-minute period of ischemia induced almost a total loss of motor neurons 2 days after reperfusion.5Suzuki K. Kazui T. Terada H. Umemura K. Ikeda Y. Bashar A.H. et al.Experimental study on the protective effects of edaravone against ischemic spinal cord injury.J Thorac Cardiovasc Surg. 2005; 130: 1586-1592Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar Therefore, the motor neuron damage in the current study was mediated mainly through necrosis, but not apoptosis. We agree that HGF might induce neuroprotective effects through inhibition of apoptotic cascade. However, it was highly impossible that the observed neuroprotection of HGF in our study is due to its antiapoptotic effects. Which cell is transferred hepatocyte growth factor gene?The Journal of Thoracic and Cardiovascular SurgeryVol. 133Issue 4PreviewI read with interest the article by Shi and associates,1 titled “Nonviral Gene Transfer of Hepatocyte Growth Factor Attenuates Neurologic Injury After Spinal Cord Ischemia in Rabbits.” It is already known that hepatocyte growth factor (HGF) functions as a powerful angiogenic factor, as well as a potent neurotrophic factor,2 and HGF is not expressed in the spinal cord in the early phase after the ischemia.3 Thus I agree that gene transfer of HGF could induce tolerance against a severe spinal cord ischemic insult. Full-Text PDF