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A dual role for reactive astrocytes after spinal cord injury
Abstracts / Neuroscience Research 58S (2007) S1–S244
S29
S3P-G4 A dual role for reactive astrocytes after spinal cord
S3P-H2 Analysis of cortical reorganization (CR) of the patients
injury
with phantom-limb pain and the mechanism of motor cortex stimulation
Seiji Okada 1 , Masaya Nakamura 2 , Yoshiaki Toyama 2 , Yukihide Iwamoto 3 , Hideyuki Okano 4 1 SSP Stem Cell Unit, Kyushu University Faculty of Medicine, Japan; 2 Department of Otrhopaedic Surgery, Keio University, Tokyo, Japan; 3 Department of Otrhopaedic Surgery, Graduate School of Medicine, Kyushu University, Fukuoka, Japan; 4 Department of Physiology, Keio University, Tokyo, Japan In the injured central nervous system, reactive astrocytes form a glial scar and are considered to be detrimental for axonal regeneration, but their function remains elusive. Here, we demonstrated that reactive astrocytes play a crucial role in wound healing and functional recovery by using mice with a selective deletion of Stat3 under the control of Nestin gene promoter/enhancer. Reactive astrocytes in Stat3 conditional knockout mice showed limited migration and resulted in markedly widespread infiltration of inflammatory cells, neural disruption and demyelination with severe motor deficits after contusive spinal cord injury. These results suggest that Stat3 is a key regulator of reactive astrocytes in the healing process after SCI, providing a potential target for intervention in the treatment of CNS injury.
S3P-G6
The two-photon microscopic analysis of cortical spreading depression Takano 1 ,
Tian 1 ,
Hansen 2 ,
Takahiro Guo-Feng Anker J. Maiken Nedergaard 1 1 Center for Aging and Developmental Biology, University of Rochester, Rochester, USA; 2 Discovery, Novo Nordisk, Maaloev, Denmark Cortical spreading depression (CSD) is a self-propagating wave of large depolarization that has been implicated in migraine and progressive neuronal injury following stroke and head trauma. Using two-photon microscopy in live mouse cortex, the propagation of CSD was visualized as a progressive wave of transient calcium flux in astrocytes. Tissue swelling was not due to astrocytic, but the neuronal swelling, with severe disfiguration of dendrites. Metabolic state monitored by NADH intrinsic fluorescence revealed that the tissue consists of two distinct areas of decrease and increase of the NADH. This distinctive NADH pattern followed neither the cellular organization nor the cell types, but outlined the vasculature. Thus, the perivascular tissue increased the rate of oxidative metabolism, causing the rest of the tissue hypoxic, even with the transient vasodilation. Our results suggest that processes of astrocytes and neurons form a metabolic unit that shares the redox state rather than having independent controls.
Youichi Saitoh, Takufumi Yanagisawa, Satoru Oshino, Masayuki Hirata, Tetsu Goto, Koichi Hosomi, Naoki Tani, Toshiki Yoshimine Department of Neurosurgery, Osaka University Graduate School of Medicine, Japan We have treated 12 patients with phantom-limb pain with motor cortex stimulation (MCS). Six of 12 patients showed pain reduction with MCS. The detailed mechanism of pain reduction with MCS has been unknown. Professor Flor suggests that phantom-limb pain was attributable to the cortical reorganization (CR). We analysed CR in phantom-limb pain with magnetic encephalography (MEG), cortical mapping by navigationguided transcranial magnetic stimulation (TMS). In the operated patients with cortical electrodes, SEP recording and motor cortical mapping were performed. And EEG was measured during various imaginal movement of phantom-limb. One patient showed remarkable CR with MEG and TMS cortical mapping, and remarkable pain reduction with MCS. Other patient could not imagine the movement of phantom-limb, and showed poor pain reduction with MCS. We would like to discuss the analysis of CR and the mechanism of MCS in the phantom-limb pain.
S3P-H3 Thalamic sensory relay nucleus stimulation and phantom limb pain Yoichi Katayama Department of Neurological Surgery, Nihon University, Tokyo, Japan The primary somatosensory cortex undergoes reorganization of receptive field representation in patients with phantom limb pain (PP). The extent of cortical reorganization and the degree of PP have been reported to be correlated. Similar reorganization has been shown within the thalamic sensory relay nucleus (nuclei ventrocaudales: VC). VC stimulation sometimes dramatically relieves chronic PP, while stimulation rarely alters phantom limb sensation itself in the same patients. This finding suggests that PP may be controlled by VC stimulation through restoration of the original cortical organization in response to artificial activation of non-functioning somatosensory pathway. It has been suggested that conscious sensation occurs only when peripheral sensory stimulus activates wide spread neural networks, including the limbic cortex, beyond the somatosensory pathway. In contrast to patients with intact somatosensory pathways, the patients with PP report various vivid somatosensory and/or somatomotor sensations. This finding indicates that perceptual level of neural networks involved in conscious sensation is heightened in these patients.
Research funds: NIH NS30007 and NS38073
S3P-H1 Analysis of pain cognition by neuroimaging study Ryusuke Kakigi Department of Integrative Physiology, National Institute for Physiological Sciences, Okazaki, Japan Electroencephalography (EEG) and magnetoencephalography (MEG) were recorded following both A-delta (first pain) and C fiber (second pain) stimulation. EEG and MEG findings following C fiber stimulation were similar to those following A-delta fiber stimulation except for a longer latency. At first, primary somatosensory cortex (SI) contralateral to the stimulation is activated and then secondary somatosensory cortex (SII), insula, amygdala and anterior cingulate cortex (ACC) in the bilateral hemispheres are activated sequentially. Event-related functional magnetic resonance imaging (fMRI) was also recorded following A-delta and C fibers stimulation. The stimulation of both C and A-delta nociceptors activated the bilateral thalamus, SII, middle insula, and Brodmann’s area (BA) 24/32. However, activity in the right BA32/8/6, including ACC and pre-supplementary motor area (pre-SMA), and the bilateral anterior insula was significantly stronger following the C fiber stimulation than A-delta fiber stimulation. These findings were probably due to the differences in the emotional and motivational aspects of either pain.
S3P-H4 Cerebral reorganization by adaptable robot hand Hiroshi Yokoi 1 , Ryu Katoh 1 , Alejandro Arieta Hernandez 1 , Tamaki Miyamoto 2 , Katsunori Ikoma 2 , Takashi Onishi 3 , Wenwei Yu 4 , Tamio Arai 1 1 Department of Precision Engineering, The University of Tokyo, Tokyo, Japan; 2 School of Medicine, Hokkaido University, Japan; 3 Radiology, National Center of Neurology and Psychiatry, Japan; 4 Department of Medical System Engineering, Chiba University, Japan The prosthetic care for the handicapped persons requires new and reliable robotics technology. This study investigates the reactions of our brain to the adaptable robot hand. The adaptable robot hand is structured EMG controlled robot hand with learning function for EMG pattern recognition for Transradial (below elbow) prostheses. The mutual adaptation among man and adaptable robot hand is analyzed by using f-MRI in order to clarify the plasticity of motor and sensory area of cortex according to the change of prosthesis. The robot hand with 13 DOF is developed that has three motors on thumb finger and two motors on each rest of four fingers, and two motors for wrist. The tactile feedback is applied by using electric stimulus. The f-MRI data shows the illusions and adaptation process of replacement from a phantom limb image to the robot hand image. Research fund: KAKENHI (16360118)
S29
S3P-G4 A dual role for reactive astrocytes after spinal cord
S3P-H2 Analysis of cortical reorganization (CR) of the patients
injury
with phantom-limb pain and the mechanism of motor cortex stimulation
Seiji Okada 1 , Masaya Nakamura 2 , Yoshiaki Toyama 2 , Yukihide Iwamoto 3 , Hideyuki Okano 4 1 SSP Stem Cell Unit, Kyushu University Faculty of Medicine, Japan; 2 Department of Otrhopaedic Surgery, Keio University, Tokyo, Japan; 3 Department of Otrhopaedic Surgery, Graduate School of Medicine, Kyushu University, Fukuoka, Japan; 4 Department of Physiology, Keio University, Tokyo, Japan In the injured central nervous system, reactive astrocytes form a glial scar and are considered to be detrimental for axonal regeneration, but their function remains elusive. Here, we demonstrated that reactive astrocytes play a crucial role in wound healing and functional recovery by using mice with a selective deletion of Stat3 under the control of Nestin gene promoter/enhancer. Reactive astrocytes in Stat3 conditional knockout mice showed limited migration and resulted in markedly widespread infiltration of inflammatory cells, neural disruption and demyelination with severe motor deficits after contusive spinal cord injury. These results suggest that Stat3 is a key regulator of reactive astrocytes in the healing process after SCI, providing a potential target for intervention in the treatment of CNS injury.
S3P-G6
The two-photon microscopic analysis of cortical spreading depression Takano 1 ,
Tian 1 ,
Hansen 2 ,
Takahiro Guo-Feng Anker J. Maiken Nedergaard 1 1 Center for Aging and Developmental Biology, University of Rochester, Rochester, USA; 2 Discovery, Novo Nordisk, Maaloev, Denmark Cortical spreading depression (CSD) is a self-propagating wave of large depolarization that has been implicated in migraine and progressive neuronal injury following stroke and head trauma. Using two-photon microscopy in live mouse cortex, the propagation of CSD was visualized as a progressive wave of transient calcium flux in astrocytes. Tissue swelling was not due to astrocytic, but the neuronal swelling, with severe disfiguration of dendrites. Metabolic state monitored by NADH intrinsic fluorescence revealed that the tissue consists of two distinct areas of decrease and increase of the NADH. This distinctive NADH pattern followed neither the cellular organization nor the cell types, but outlined the vasculature. Thus, the perivascular tissue increased the rate of oxidative metabolism, causing the rest of the tissue hypoxic, even with the transient vasodilation. Our results suggest that processes of astrocytes and neurons form a metabolic unit that shares the redox state rather than having independent controls.
Youichi Saitoh, Takufumi Yanagisawa, Satoru Oshino, Masayuki Hirata, Tetsu Goto, Koichi Hosomi, Naoki Tani, Toshiki Yoshimine Department of Neurosurgery, Osaka University Graduate School of Medicine, Japan We have treated 12 patients with phantom-limb pain with motor cortex stimulation (MCS). Six of 12 patients showed pain reduction with MCS. The detailed mechanism of pain reduction with MCS has been unknown. Professor Flor suggests that phantom-limb pain was attributable to the cortical reorganization (CR). We analysed CR in phantom-limb pain with magnetic encephalography (MEG), cortical mapping by navigationguided transcranial magnetic stimulation (TMS). In the operated patients with cortical electrodes, SEP recording and motor cortical mapping were performed. And EEG was measured during various imaginal movement of phantom-limb. One patient showed remarkable CR with MEG and TMS cortical mapping, and remarkable pain reduction with MCS. Other patient could not imagine the movement of phantom-limb, and showed poor pain reduction with MCS. We would like to discuss the analysis of CR and the mechanism of MCS in the phantom-limb pain.
S3P-H3 Thalamic sensory relay nucleus stimulation and phantom limb pain Yoichi Katayama Department of Neurological Surgery, Nihon University, Tokyo, Japan The primary somatosensory cortex undergoes reorganization of receptive field representation in patients with phantom limb pain (PP). The extent of cortical reorganization and the degree of PP have been reported to be correlated. Similar reorganization has been shown within the thalamic sensory relay nucleus (nuclei ventrocaudales: VC). VC stimulation sometimes dramatically relieves chronic PP, while stimulation rarely alters phantom limb sensation itself in the same patients. This finding suggests that PP may be controlled by VC stimulation through restoration of the original cortical organization in response to artificial activation of non-functioning somatosensory pathway. It has been suggested that conscious sensation occurs only when peripheral sensory stimulus activates wide spread neural networks, including the limbic cortex, beyond the somatosensory pathway. In contrast to patients with intact somatosensory pathways, the patients with PP report various vivid somatosensory and/or somatomotor sensations. This finding indicates that perceptual level of neural networks involved in conscious sensation is heightened in these patients.
Research funds: NIH NS30007 and NS38073
S3P-H1 Analysis of pain cognition by neuroimaging study Ryusuke Kakigi Department of Integrative Physiology, National Institute for Physiological Sciences, Okazaki, Japan Electroencephalography (EEG) and magnetoencephalography (MEG) were recorded following both A-delta (first pain) and C fiber (second pain) stimulation. EEG and MEG findings following C fiber stimulation were similar to those following A-delta fiber stimulation except for a longer latency. At first, primary somatosensory cortex (SI) contralateral to the stimulation is activated and then secondary somatosensory cortex (SII), insula, amygdala and anterior cingulate cortex (ACC) in the bilateral hemispheres are activated sequentially. Event-related functional magnetic resonance imaging (fMRI) was also recorded following A-delta and C fibers stimulation. The stimulation of both C and A-delta nociceptors activated the bilateral thalamus, SII, middle insula, and Brodmann’s area (BA) 24/32. However, activity in the right BA32/8/6, including ACC and pre-supplementary motor area (pre-SMA), and the bilateral anterior insula was significantly stronger following the C fiber stimulation than A-delta fiber stimulation. These findings were probably due to the differences in the emotional and motivational aspects of either pain.
S3P-H4 Cerebral reorganization by adaptable robot hand Hiroshi Yokoi 1 , Ryu Katoh 1 , Alejandro Arieta Hernandez 1 , Tamaki Miyamoto 2 , Katsunori Ikoma 2 , Takashi Onishi 3 , Wenwei Yu 4 , Tamio Arai 1 1 Department of Precision Engineering, The University of Tokyo, Tokyo, Japan; 2 School of Medicine, Hokkaido University, Japan; 3 Radiology, National Center of Neurology and Psychiatry, Japan; 4 Department of Medical System Engineering, Chiba University, Japan The prosthetic care for the handicapped persons requires new and reliable robotics technology. This study investigates the reactions of our brain to the adaptable robot hand. The adaptable robot hand is structured EMG controlled robot hand with learning function for EMG pattern recognition for Transradial (below elbow) prostheses. The mutual adaptation among man and adaptable robot hand is analyzed by using f-MRI in order to clarify the plasticity of motor and sensory area of cortex according to the change of prosthesis. The robot hand with 13 DOF is developed that has three motors on thumb finger and two motors on each rest of four fingers, and two motors for wrist. The tactile feedback is applied by using electric stimulus. The f-MRI data shows the illusions and adaptation process of replacement from a phantom limb image to the robot hand image. Research fund: KAKENHI (16360118)