Changes in the lactate threshold during treadmill exercise after microsphere-induced infarction in rats.

The aim of this study was to clarify changes in the lactate threshold (LT) in the acute period after cerebral infarction. Cerebral infarction was induced by the injection of microspheres (MS) into the right internal carotid artery. To estimate the degree of neurologic deficit caused by surgery, the behaviors of all rats were evaluated in terms of typical symptoms of stroke in rats. The rotarod test was used to evaluate equilibrium function. Rats were forced to perform stepwise treadmill exercises, and serial changes in blood lactate concentration were measured for determination of the LT. The average treadmill speed at the LT and the rotarod test performance in MS rats was significantly lower than those in sham-operated rats on postsurgery day 2. However, although neurologic deficits disappeared on postsurgery day 7 in MS rats, LT level and rotarod test performance were significantly lower than in sham-operated rats. These results suggest that the decrease in LT in the acute period after cerebral infarction might be induced by impaired equilibrium function. Other possibilities are discussed as well

視覚性入力により誘発される悪心とそれに伴う自律神経反応

本研究は,ヒトにおいて生体防御反応の一つである嘔吐の前兆現象である悪心に至るまでの自律神経反応を定量的に解析することを目的とした.悪心を誘発させるために,低頻度かつ不規則な振動および回転などを加えたビデオ画像,すなわち動揺性視覚刺激を健常成人19名に注視させた.悪心の自覚症状は,実験前後に行った13項目にわたるアンケート調査の各項目について,5段階評価の回答を得て数値化した.回答値の平均スコアを実験前後で比較したところ自覚症状は有意に悪化した(P<0.001).動揺性視覚刺激中に,自律神経反応の指標として,胃電図,心電図,呼吸運動,手掌部発汗量,前額部発汗量および指尖部末梢血流量の変化を連続的に測定した.視覚刺激を与えない状態をコントロール(第1相)として,ビデオ放映時の前半3分を第2相,後半3分を第3相,ビデオ放映後5分間を第4相とし,コントロール時の値と比較検討した.胃電図より解析した胃運動の振幅は第3相においてコントロールと比べ有意に増加した(P<0.05).しかし,胃運動の周波数成分である徐波,正常波,および頻波それぞれ振幅が全振幅に占める割合には,徐波が減少する傾向はあるものの有意な差は認められなかった.心電図により解析した平均心拍数はコントロールに比べ第2相で有意に減少したが(P<0.05),この減少は一過性であった.呼吸数はコントロールに比べ,ビデオ放映中有意に増加した(P<0.05).手掌部の発汗には,実験中有意な増減は見られなかったが,前額部の発汗はビデオ放映中有意な増加が見られた(P<0.05).また指尖部末梢血流量については,第2相で有意な減少が見られたが(P<0.05),それ以降では有意な増減は認められなかった.さらに,空腹群(6名)と食後群(13名)の胃電図上の変化を比較した結果,空腹群では第2相における振幅増加が抑えられる傾向が見られた.悪心の自覚症状においても食後群の悪心スコアは空腹群に比べて有意に高い値を示した(P<0.05).以上より,悪心という自覚症状の発生に至る過程において,交感性及び副交感性の自律神経反応が出現していることが明らかになった.In this study, the autonomic nervous reactions accompanying nausea induced by visual stimulation were analyzed quantitatively in humans. Nineteen healthy subjects who were sitting, and who were both physically rested and relaxed, were exposed to a six-minute oscillating movie as visual stimulation. Before, during and after watching the movie, gastric myoelectric activities (EGG), heart rate (ECG), erspiration frequency, perspiration volume from the surface of the right plam and forehead, and peripheral blood flow in a forefinger were measured in each subject. These items were analyzed as an index of autonomic nervous activities. The examination period was divided into four phases, i. e., phase 1 : control, phase 2 : the first half of watching the movie, phase 3 : the latter half of watching the movie and phase 4 : the five minute period after watching the movie. The scores for 13 items of subjective symptoms, which the subjects were questioned about before and after watching the movie, showed that the visual stimulation sufficiently evoked nausea. Analysis of the EGGs showed that the amplitude of gastric myoelectric activities were augmented in phase 3 as compared to those in phase 1 (P<0.05). However, distribution of amplitude of bradygastria, normalgastria and tachygastria did not change significantly among the phases. The heart rate decreased in phase in phase 2 (P<0.05), but this decrease was decrease was temporay and soon returned to the control level. The respirtion frequency increased during the phases 2 and 3 (P<0.05). The perspiration volume from the palm showed no change during the examination but that from the forehead increased during watchnig the movie (P<0.05). Peripheral blood flow temporarily decreased in phase 2 (P<0.05), but returned to the control level in the following phases. In 6 fasting subjects, augmentation of EGG amplitude in phase 2 was smaller than that in the other 13 postprandial subjects. The subjective nausea symptoms score in the fasting subjects was lower than that in the postprandial subjects (P<0.05). The expressions of these atuonomic nervous reactions were presumed to be the preparations for vomiting, and the results of unconscious activieties to prevent the transition to vomiting from nausea. In conclusion, nausea is attended by fast and temporay parasympathetic nervous activity and the mixture of sympathetic and parasympatetic nervous activities in the latter phases

Impacts of Age and Gender on Brain Edema in a Mouse Water Intoxication Model

Brain edema causes abnormal fluid retention and can be fatal in severe cases. Although it develops in various diseases, most treatments for brain edema are classical. We analyzed the impacts of age and gender on the characteristics of a water intoxication model that induces pure brain edema in mice and examined the model’s usefulness for research regarding new treatments for brain edema. C57BL/6J mice received an intraperitoneal administration of 10% body weight distilled water, and we calculated the brain water content by measuring the brain-tissue weight immediately after dissection and after drying. We analyzed 8-OHdG and caspase-3 values to investigate the brain damage. We also applied this model in aquaporin 4 knockout (AQP4−) mice and compared these mice with wild-type mice. The changes in water content differed by age and gender, and the 8-OHdG and caspase-3 values differed by age. Suppression of brain edema by AQP4− was also confirmed. These results clarified the differences in the onset of brain edema by age and gender, highlighting the importance of considering the age and gender of model animals. Similar studies using genetically modified mice are also possible. Our findings indicate that this water intoxication model is effective for explorations of new brain edema treatments

The angiogenesis and functional recovery effect after spinal cord injury by newly synthesized nucleotide analog, COA-Cl

　2-chloro-carbocyclic oxetanocin A（COA-Cl）はアデノシン類似体合成化合物であり in vitro にて血管新生作用が報告されており，またラットの脳卒中モデルに対する投与で神経保護，血管新生および機能回復効果が示されている．本研究ではこれらの効果が脊髄損傷モデルにおいても発揮されるか否かを評価した．荷重装置により T9レベルの脊髄損傷モデルラットを作製し，損傷直後から COA-Cl を５日間腹腔内投与した COA-Cl 群と，同量の生理食塩水を投与した vehicle群に分けた．脊髄損傷14日後に運動機能を Basso-Beattie-Bresnahan Locomotor Rating Scale スコア（BBB スコア）と傾斜台試験にて，血管新生をラミニンの免疫染色により後索の血管数と血管面積を測定することで評価した．運動機能は BBB スコアと傾斜台試験ともに COA-Cl 群でvehicle 群に比べて有意に改善した．血管新生は COA-Cl 群で血管数および血管面積ともに有意に増加した．これらの結果から，COA-Cl の脊髄損傷後急性期における投与は運動機能改善および血管新生をもたらし，脊髄損傷急性期の新規治療薬としての可能性が示された．　2-chloro-carbocyclic oxetanocin A (COA-Cl), a novel synthesized adenosine analog, has been reported to have a strong angiogenic effect. In our previous study using a rat model of stroke, we showed the neuroprotective, angiogenic and motor recovery effects of COACl. Spinal cord injury (SCI) induces severe motor dysfunction and lowers the quality of life. In our recent study, we demonstrated that acute-phase administration of COA-Cl protects against spinal cord damage and facilitates motor recovery after SCI. In this study, we hypothesized that acute-phase administration of COA-Cl post-SCI also induces early neovascularization and participates in motor function recovery. SCI was induced using a drop device in rats. Rats with SCI were divided into 2 groups: COA-Cl and vehicle groups (n = 5 in each group). COACl was intraperitoneally injected (6 mg/kg in saline) once a day for 5 days immediately after SCI. In the vehicle group, only saline was administered, with the same dosing regimen as that in the COA-Cl group. Fourteen days after SCI, motor function was evaluated based on Basso–Beattie–Bresnahan scoring and the inclined plane test. To evaluate angiogenesis, cryosections of the spinal cord were immunostained with anti-laminin antibody. Motor function significantly improved in the COA-Cl group compared with that in the vehicle group; concomitantly, both the number and volume of blood vessels significantly increased in the COA-Cl group compared with those in the vehicle group. In conclusion, acute-phase administration of COA-Cl results in motor function recovery, which may be attributed to angiogenic effects

視覚性入力により誘発される悪心とそれに伴う自律神経反応

原

Data from: Rehabilitative skilled forelimb training enhances axonal remodeling in the corticospinal pathway but not the brainstem-spinal pathways after photothrombotic stroke in the primary motor cortex

Task-specific rehabilitative training is commonly used for chronic stroke patients. Axonal remodeling is believed to be one mechanism underlying rehabilitation-induced functional recovery, and significant roles of the corticospinal pathway have previously been demonstrated. Brainstem-spinal pathways, as well as the corticospinal tract, have been suggested to contribute to skilled motor function and functional recovery after brain injury. However, whether axonal remodeling in the brainstem-spinal pathways is a critical component for rehabilitation-induced functional recovery is not known. In this study, rats were subjected to photothrombotic stroke in the caudal forelimb area of the primary motor cortex and received rehabilitative training with a skilled forelimb reaching task for 4 weeks. After completion of the rehabilitative training, the retrograde tracer Fast blue was injected into the contralesional lower cervical spinal cord. Fast blue-positive cells were counted in 32 brain areas located in the cerebral cortex, hypothalamus, midbrain, pons, and medulla oblongata. Rehabilitative training improved motor performance in the skilled forelimb reaching task but not in the cylinder test, ladder walk test, or staircase test, indicating that rehabilitative skilled forelimb training induced task-specific recovery. In the histological analysis, rehabilitative training significantly increased the number of Fast blue-positive neurons in the ipsilesional rostral forelimb area and secondary sensory cortex. However, rehabilitative training did not alter the number of Fast blue-positive neurons in any areas of the brainstem. These results indicate that rehabilitative skilled forelimb training enhances axonal remodeling selectively in the corticospinal pathway, which suggests a critical role of cortical plasticity, rather than brainstem plasticity, in task-specific recovery after subtotal motor cortex destruction