New therapeutic advances in CNS injury and repair

Abstract

9th Global College of Neuroprotection & Neuroregeneration (GCNN) Annual Conference

Xi’an, Shaanxi Province, China, 4–7 May 2012

The 9th Global College of Neuroprotection and Neuroregeneration annual meeting was held in cooperation with the 5th International Association of Neurorestoratology and the 4th International Spinal Cord Injury Treatment and Trial Symposium in the beautiful city of Xi’an, Shaanxi Province, China, between 4 and 7 May 2012. This trilateral conference was held in the pleasing ambience of the Sofitel Hotel Complex in Renmin Square, Xi’an. Top Chinese government dignitaries including the National Deputy Health Minister, Vice Governor of Shaanxi Province, Vice President of Xi’an Jiaotong University and Party Secretary of the Medical Association inaugurated the congress. More than 1000 delegates from across the world, including approximately 600 medical researchers from China, participated in this meeting. The theme of this meeting was ‘neurorestoration and neurorepair’ using stem cell treatment, antibodies and pharmacotherapy, as well as nanomedicine and neurorehabilitation. Preclinical and clinical research was presented and discussed. Use of nanomedicine to enhance neurorepair or diagnosis of neurological diseases in clinical situations was the new attraction in this trilateral meeting. More than 50 leading experts in neuroprotection and neurorestoratology presented their cutting edge research in the area. New features included the Youth Forum in which 12 young scientists presented their innovative results, and more than 30 platform presentations were included. Thus, the trilateral conference of the Global College of Neuroprotection and Neuroregeneration, the International Association of Neurorestoratology and the International Spinal Cord Injury Treatment and Trial Symposium was extremely successful from both the scientific and social perspectives.

Keywords::

• blood–brain barrier
• brain edema
• CNS injury
• nanomedicine
• neuroregeneration
• patient care
• pharmacotherapy
• spinal cord injury
• stem cell therapy

Following the great success of the 8th Global College of Neuroprotection and Neuroregeneration (GCNN) meeting (in collaboration with the 4th International Association of Neurorestoratology [IANR] and the 11th American Society for Neural Therapy & Repair [ASNTR]) in Amman, Jordan [1], the 9th GCNN congress (Founder President Hari Sharma, Uppsala University Hospital, Uppsala, Sweden) in cooperation with the 5th IANR (Founder President Hongyun Huang, Beijing Rehabilitation Center, Beijing, China) and the 4th International Spinal Cord Injury Treatment and Trial Symposium (ISCITT; Founder President Wise Young, Rutgers University, NJ, USA) was organized under the chairmanship of Xijing He (Second Hospital of Xi’an Jiaotong University, Xi’an, China) in Sofitel, Xi’an, China on 4–7 May 2012. During the 3-day scientific extravaganza, over 105 speakers presented their novel research in this trilateral meeting series. The congress was attended by more than 1200 delegates including representatives of medical instruments and logistic companies as well as giants of pharmaceutical industries from across the globe. Several medical students, teachers, researchers and policy makers from China and abroad also participated in the event. The scientific committee of the joint congresses series comprising Geoffrey Raisman (University College London, London, UK), Hongyun Huang and Wise Young invited 50 keynote speakers from all over the world. There were seven core presentations from the founding fathers and policy makers of these organizations. In addition, a Youth Forum was organized to encourage young investigators to present their findings in front of a panel of renowned scientists. The three best presentations were awarded from among the 12 participants based on the data quality, the speakers’ presentation and subject matter of the investigations. In addition, 50 platform presentations were selected in various categories related to neuroprotection and neurorestoration. In this meeting, active collaboration among neuroscientists was encouraged by the leaders of the core organization for the further development of the subject.

The first day of the Congress was devoted to the clinical trials on spinal cord injury (SCI) conducted by ISCITT (Founder President Wise Young). In addition, the Youth Forum was included on the first day of the congress program. The first session of SCI trials from the industry perspectives consisted of eight keynote speeches and 21 platform presentations.

In the ISCITT session, human spinal cord-derived neural stem cells for the treatment of neurological diseases was described by Karl Johe (NeuralStem, Inc., MD, USA). Casey Case (SanBio, Inc., CA, USA) presented a treatment opportunity for chronic stroke and SCI using gene-modified mesenchymal stem cells to enhance neuroregeneration [2,3]. Lisa McKerracher (Bioaxone Biosciences, FL, USA) described the successful results of cethrin treatment in clinical trials of SCI, and Daniel Lee (Roche, CA, USA) discussed neuroprotection in SCI by Nogo receptor blockade [4,5]. Wise Young emphasized the umbilical cord blood mononuclear cell therapy for improving functional recovery in stroke and SCI patients [6]. An overview on Celgene Cellular Therapeutics by Ralph Fariello (Celgene Cellular Therapeutics, NJ, USA) and cell-based therapy by Mahendra Rao (NIH, MD, USA) in stroke and SCI was given in great detail [7,8]. Other topics covered by platform presentations in this session by Chinese Associations of Neurorestoratology include various stem cell transplantations in SCI or stroke patients for therapeutic benefit in a large number of cases. In Youth Forum studies on stem cell transplantation, neurotrophic factor therapy and nanodelivery of cyclosporine to treat SCI, stroke, cerebral palsy and other neurodegenerative diseases were discussed by young researchers from across the globe.

The scientific importance of this trilateral meeting was emphasized by the fact it was attended by top dignitaries of the central and regional offices of the Chinese Government. The Chief Guest of the Ceremony, Dakui Yin, the National Deputy Health Minister of China, welcomed the delegates and called for joint efforts by the international community to find a cure for CNS injuries. Xiamimg Zheng (Governor of Shaanxi Province, Xi’an) and Mingshao Liu (Health Minister of Shaanxi Province) commended this joint meeting as a landmark of international cooperation. Kequin Rao (Party Secretary of the Chinese Medical Association [Beijing]) and Jianqun Yan (Vice President of Xi’an Jiaotong University) requested for continuation of such joint meetings to improve healthcare by conducting more basic research in this area.

The opening ceremony was followed by seven core presentations by the organizers and Presidents of the respective societies on the focal theme of the congress to set the stage of the meeting and to provide an overall scope of research and development to the young students. Geoffrey Raisman discussed the new challenges in neurorestoratology [9]. Hongyun Huang presented the state-of-the-art development in neurorestoratology [10]. He also presented the need for interaction among various neuroprotective organizations and societies from across the world for further development of the subject. Ziad Al-Zoubi (Jordan Ortho & Spinal Centre, Amman, Jordan; Current President of IANR) presented the role of stem cell-related international cooperation and scope for treatment of CNS and orthopedic diseases. The role of pharmacotherapy in neurorestoratology, with special emphasis on CNS injury and repair, was presented in detail by Hari S Sharma (President, GCNN and elected President of IANR [11–13]). Milan Dimetrijevic (Baylor College of Medicine, TX, USA) discussed electrophysiological monitoring of spinal cord neuromodulation using motor control functions in human cases. Wise Young described the recent progress of SCI treatment in relation to neurorestoratology [6,14]. Follow-up cases of SCI patients after transplantation of olfactory ensheathing cells and progress in their lifestyle were presented by Xijing He.

After core presentations, four sessions were designed to cover 26 talks on neurorestoratology of spinal cord or nerve repair mechanisms (eight speakers), in pediatric cases (four speakers), traumatic/ischemic injuries (ten talks) and geriatric situations (four presentations). Kwok-Fai So (University of Hong Kong, Hong Kong, China) discussed the significance of adult neural stem cells in nerve injury and repair. Joel Glover (The Norwegian Center for Stem Cell Research, Oslo, Norway) showed human stem cell-induced neurorecovery in a neonatal mouse model of SCI using a functional imaging technique. Woei-Cheng Shyu (China Medical University Hospital, Taiwan, China) discussed stereotaxic implantation of olfactory ensheathing cells in stroke patients, whereas the use of umbilical cord blood cells in SCI and nerve injury was described by three speakers (Gilberto Leung, Kent Tsang and David Sun) from the Chinese University of Hong Kong (Hong Kong, China). The role of mouse cells from adult human pluripotent stem cells (Mari Dezawa, Tohoku University, Yohoku, Japan) and reprogramming of somatic cells (Duanqing Pei, Tsinghua University, Beijing, China) were discussed in regenerative medicine in human cases.

In the pediatric neurorestoratology session, William Slikker Jr (US FDA and National Center for Toxicological Research, AR, USA) discussed anesthesia-induced neurotoxicity in the developing brain and the role of drugs in inducing neuroprotection [15]. Zuo Luan (Navy General Hospital, Beijing, China) presented precursor cell transplantation for the treatment of visually impaired children. Integrative regenerative therapy for autism and related disabilities was described by Yehia Yousif (Batterjee Medical College for Science and Technology, Jeddah, Saudi Arabia). Alok Sharma (Lokmanya Tilak Municipal Medical University, Mumbai, India) presented clinical results on stem cell transplantation in muscular dystrophy.

In the general neurorestoratology session, Geoffrey Raisman presented the repair of SCI in a rat model with caution and hope using stem cells and neurotrophins. Hari Sharma discussed the new role of monoclonal antibodies against harmful neurochemicals such as dynorphin A, serotonin, histamine, nitric oxide synthase and TNF-a for neuroprotection in SCI [16–18]. In addition, the superior neuroprotective effects of neurochemical modulation by receptor or synthesis blocker drugs and a combination of different neurotrophic factors (i.e., cerebrolysin) delivered through nanotechnology were discussed in a rat model of SCI [17–20]. Andrey S Bryukhovetskiy (Russian State Medical University, Moscow, Russia) gave new evidence using the profile of stem cell proteome for the development of personalized cell preparations to enhance regenerative therapy for neurological disorders. Dafin F Muresanu (Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania) showed neurotrophic factors and cerebrolysin treatment in Alzheimer’s disease [21]. Dajue Wang (China Rehabilitation Research Centre, Beijing, China) emphasized the problems of cognitive neural rehabilitation in patients after an attack of stroke or other neurological diseases. In this session, Nanbert Zhong (Peking University, Beijing, China) critically reviewed the use of stem cell transplantation for neurological disorders. Giovanni Tosi (University of Modena and Reggio Emilia, Modena, Italy) discussed the modes of nanodrug delivery to enhance neuroprotection for CNS injury in animal models. Gustavo Moviglia (National University of La Plata, Buenos Aires, Argentina) emphasized on four key aspects for the recovery of patients with complete SCI using stem cell transplantation and therapy. A need for the international accreditation of stem cell therapy was discussed by Adeeb Al-Zoubi (University of Illinois College of Medicine, IL, USA). Seyed Hassan Emami-Razavi (Tehran University of Medical Sciences, Tehran, Iran) presented the coding and traceability of stem cell and tissue products in Iran.

In the session on geriatric neurorestoratology, Lin Chen (Beijing Rehabilitation Center, Beijing, China) described the beneficial effects of stem cell therapy in stroke patients. Intracerebral implantation of stem cells to promote cerebrospinal tracts in stroke victims was described by Shinn-Zong Lin (Beigang Hospital of China Medical University, Taiwan, China). Barry Hoffer (Case Western Reserve University School of Medicine, OH, USA) discussed neurorestoration strategies using neurotrophic factors in Parkinson’s disease. Gang Li (The Chinese University of Hong Kong, Hong Kong, China) presented the distraction osteogenesis technique for stroke management in clinical situations.

On the third day (6 May), there were 40 presentations, divided into five sessions on traumatic neurorestoratology (21 speakers), neurorestorative pharmacotherapy (five speakers), neuromodulation (three talks), tissue engineering and bioengineering (two talks) and basic, general neurorestoratology or others (nine talks).

Ziad Al-Zoubi presented long-term follow-up of patients with SCI after stem cell therapy. Tiansheng Sun (Beijing Army General Hospital, Beijing, China) showed remarkable improvement in patients with complete SCI after transplantation of fetal olfactory ensheathing glial cells, and Shaocheng Zhang (Changhai Hospital of Second Military Medical University, Shanghai, China) showed that nerve reconstruction after side-to-side nerve suture could restore function. Wagih S El Masri (Robert Jones and Agnes Hunt Orthopaedic Hospital, Shropshire, UK) suggested different interventions like ambulation both indoors and outdoors as an added value in recovery following traumatic SCI. Ali Atom (King Hussein Medical Center, Amman, Jordan) suggested implanting stem cells into the injury site for better recovery. Maria T Moviglia (Neurorehabilitation Department, Buenos Aires, Argentina) showed that a combination of cellular therapy with mild ambulatory movement of the head, hand, legs and other maneuvers improves the patients’ conditions dramatically. Jianjun Li (China Rehabilitation Research Center, Beijing, China) discussed myelotomy for the treatment of SCI. Mobilization of bone marrow progenitor cells for regenerative therapy following traumatic brain injury was presented by Elens Rem Chernykh (Clinical Hospital No. 1 and No. 34, Novosibirsk, Russia). Peripheral axonal regeneration and neurological recovery with blood-borne cells was demonstrated by Damien Kuffler (University of Puerto Rico, Puerto Rico). Koichi Iwatsuki (Osaka University Medical School, Osaka, Japan) used olfactory mucosal cell transplantation for the treatment of chronic SCI with great success in clinical trials in Japan. Hooshang Sabri (Tehran University, Tehran, Iran) demonstrated the safe use of granulocyte colony stimulating factor in treating SCI cases. Shiqing Feng (Tianjin Medical University General Hospital, Tianjin, China) showed long-term results of the follow-up of six SCI patients after treatment with autologous-activated Schwann cells with remarkable recovery. Maria Zhukova (Russian State Medical University, Moscow, Russia) presented comparative studies on long-term stem cell therapies from various origins in human SCI cases. Successful treatment of delayed encephalopathy after carbon monoxide intoxication with umbilical cord blood mononuclear cells was demonstrated by Fabin Han (The Affiliated Liaocheng Hospital, Shandong, China). The Iranian group from Tehran University of Medical Sciences in Tehran presented interesting talks on SCI in patients dealing with robotic-assisted gait training (Fatemeh Ghiasi and Mohammad Reza Hadian), autologous intramedullary nerve grafts (Nazi Derakhshan Rad), psychological problems (Zhara Khazeipour) and cardiovascular and metabolic risks in patients suffering from complete or incomplete SCI (Hadis Sabour). Robotic training of paraplegic patients was also discussed by Xuerang Liu (Shaanxi FuyinZhongda Technology Co., Ltd., Shaanxi, China), and Shaoyu Liu (The First Affiliated Hospital, Sun Yat-Sen University, Guangdong, China) described the contribution of high-mobility group box-1 and its receptors to proinflammatory responses in acute SCI cases.

In the pharmacotherapy session, Yasuo Iwasaki (Toho University Medical Center Omori Hospital, Tokyo, Japan) showed neuroprotective effects of bromocriptine, a D2 receptor agonist, on sciatic nerve crush-induced damage of motor neurons in both in vitro and in vivo conditions. Stephen Skaper (University of Padova, Padova, Italy) described protein kinases as therapeutic targets in CNS injury and Alzheimer’s disease [22]. Conrad Johanson (Brown University Medical School, RI, USA) demonstrated the role of augurin, a new peptide, in regulating periventricular neurogenesis following traumatic brain injuries [23]. Protective effects of crocin in SCI in rats were suggested by Bijan Forogh (Tehran University of Medical Sciences, Tehran, Iran), and Abbas Norouzi Javidan (Tehran University of Medical Sciences) showed beneficial effects of calcium and vitamin D in SCI patients.

In the neuromodulation session, Guoming Luan (Beijing Sanbo Brain Hospital, Beijing, China) showed improvement in the prognosis of seizures by neuromodulating drugs in human cases. Harry Steinbusch (Maastricht University, Maastricht, The Netherlands) discussed deep brain stimulation and neurogenesis in relation to neuroprotection in stroke models and in Huntington’s disease [24,25]. Electrical stimulation-induced neural stem cell differentiation and alignment was demonstrated by Bing Song (Cardiff University, Cardiff, UK). In the tissue engineering and bioengineering session, Russell J Andrews (NASA Ames Research Center, CA, USA) described novel aspects of nanotechnology for neurorestoration. The therapeutic effects of electrospun Tussah silk fibroin nanofibers on growth and differentiation of mesenchymal stem cells was presented by Huanxiang Zhang (Medical College of Soochow University, Jiangsu, China).

In the basic neurorestoratology session, Weiming Duan (Capital Medical University, Beijing, China) presented the regulated delivery of glial-derived neurotrophic factor gene using bone marrow-derived stem cells transduced with lentiviral vector into the mouse brain for neurorepair of a Parkinson’s disease model. The repair of spinal nerve roots in rats by transplantation of olfactory ensheathing cells was shown by Ying Li (UCL Institute of Neurology, London, UK). Daqing Li (UCL Institute of Neurology) presented the bipolarity of olfactory ensheathing cells on electrospun nanofibers for enhanced neurorecovery. Yanchao Qi (Affiliated Cancer Hospital in Guangzhou, Guangdong, China) used a combination of acupuncture and neural stem cell therapy in newborn rats to successfully treat cerebral palsy. Neuroprotection by stem cells in traumatic axonal injuries was demonstrated by Ping Wu (Cullen Neuroscience Laboratory, IL, USA). The neuroprotective potential of human cord blood and umbilical cord cells in neurodegenerative diseases was critically analyzed by Barbara Lukomska (Polish Academy of Sciences, Warsaw, Poland). Anna Sanowaska (Polish Academy of Sciences) presented the use of Wharton jelly as a natural scaffold and a rich source of mesenchymal stem cells for therapeutic use in hippocampal neurorestoration after injury in rats. Siwei You (Fourth Military Medical University, Xi’an, China) discussed the neuroprotective effects of diazepam on retinal ganglion cells after optic nerve transaction in adult rats. Finally, Xiaohua Jiang (The Chinese University of Hong Kong, Hong Kong, China) showed enhanced neuronal differentiation in de-differentiated human bone marrow-derived mesenchymal cells in a cell culture model of neuronal injury.

Thus, the fifth IANR and ninth GCNN meeting saw many new data and novel approaches in neuroprotection and neurorestoration that stimulated lively discussions from students and researchers alike, indicating the success of the joint conference in Xi’an. The sixth IANR and the tenth GCNN will be held in Bucharest, Romania between 4 and 7 April 2013. All are welcome!

Disclosure

The views expressed in this report are solely of the authors and in no way represent official positions of any granting authority or government organizations listed in the financial and competing interests disclosure.

Financial & competing interests disclosure

The authors’ research was supported by grants from the European Office of Aerospace Research & Development (London, UK), Wright Patterson Air Force Base (Dayton, OH, USA), Uppsala University (Sweden), Department of Biotechnology at the Ministry of Science & Technology (New Delhi, India), Medical Research Council (New Delhi, India), Swedish Medical Research Council (Stockholm, Sweden), Alexander von Humboldt Foundation (Bonn, Germany), Göran Gustafsson Foundation (Stockholm, Sweden) and Astra-Zeneca (Mölndal, Sweden). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.