Therapeutic potential of AMPA receptor antagonist perampanel against cerebral ischemia: beyond epileptic disorder

<正>Stroke is a leading cause of mortality and severe neurological disability worldwide; however, curative therapeutic options are limited. Although recanalization therapy using endovascular thrombectomy has demonstrated great benefits in the functional outcome of patients with acute ischemic stroke, the rate of excellent clinical outcomes remains limited. Therefore, the current recanalization     

Effects of obstructive jaundice on neutrophil production and acquisition of chemotactic activity in the bone marrow

Background and Aims:  Increased numbers and enhanced functions of peripheral neutrophils have been observed in obstructive jaundice. However, the effects of obstructive jaundice on the bone marrow, that is neutrophil production and acquisition of neutrophil chemotactic activity, have been poorly understood. In the present study, differentials of bone marrow cells and chemotactic activity of bone marrow neutrophils were evaluated in bile duct-obstructed rats.
Methods:  Male Wistar rats underwent either bile duct obstruction for 10 days or bile duct obstruction for 4 days followed by 6 days' internal biliary drainage. Differentials of peripheral blood and bone marrow cells were sequentially determined. Chemotactic activity of peripheral and bone marrow neutrophils was evaluated with a modified Boyden method using interleukin-8 (recombinant rat Gro-β) as a chemoattractant.
Results:  Numbers of peripheral neutrophils significantly increased after bile duct obstruction. Significant increases in the myeloid/erythroid (M/E) ratio of bone marrow cells were observed after bile duct obstruction. The neutrophil proliferative pool (promyelocytes and myelocytes) increased initially, followed by an increased neutrophil storage pool (metamyelocytes, bands, and segmented neutrophils). The M/E ratio as well as the neutrophil proliferative and storage pools normalized after internal biliary drainage. Chemotactic activity was enhanced in both peripheral and bone marrow neutrophils after bile duct obstruction, and enhanced chemotaxis was alleviated with internal biliary drainage.
Conclusion:  The present results strongly suggest the principal role of the bone marrow in increasing the number of neutrophils and their chemotactic activity during obstructive jaundice.     

Bilateral symmetric tonic posturing suggesting propagation to the supplementary motor area in a patient with precuneate cortical dysplasia.

We report a patient manifesting seizures with bilateral symmetric tonic posturing, which were markedly reduced after resection of the left precuneus. A 16-year-old man had sudden onset, complex partial seizures with bilateral symmetric tonic posturing since the age of eight years. Magnetic resonance fluid-attenuated inversion-recovery imaging revealed a hyperintense lesion in left precuneus. In almost all focal seizures recorded during an invasive EEG evaluation, ictal onset was detected from the inferomesial aspect of the lesion, but fast paroxysmal discharges from the ipsilateral supplementary motor area (SMA) were observed just before the clinical onset. After surgical excision of the EEG onset zone, including the lesion, seizure frequency was markedly (> 95%) reduced. By the 20th month after surgery, there were only brief nocturnal seizures involving slight elevation of both shoulders and slight abduction of both arms, with preservation of consciousness occurring once every few days. Invasive EEG findings and surgical outcome suggested that the epileptic activity originating from the epileptogenic zone may have propagated to the symptomatogenic zone including mainly the ipsilateral SMA. In summary, we report an interesting case of bilateral symmetric tonic posturing suggesting propagation to the SMA. MRI and invasive EEG confirmed the epileptogenic focus as a precuneate cortical dysplasia lesion.[Published with video sequences].     

A protease inhibitor attenuates gastric erosions and microcirculatory disturbance in the early period after thermal injury in rats

The effects of camostat mesilate, a synthetic serine protease inhibitor on gastric microcirculation and active oxygen species generated by leucocytes from the gastric and jugular veins in the early period after thermal injury were assessed. Male Wistar rats were anaesthetized and a 30% full skin-thickness dorsal burn was inflicted. Camostat mesilate (100 mg/kg) was dissolved in distilled water and administered orally to rats 40 min before thermal injury (the camostat group). The control animals (the vehicle group) were administered distilled water orally. Rolling leucocytes as well as Monastral blue B deposits in venules were observed using in vivo microscopy. Active oxygen species were measured by chemiluminescence. Camostat mesilate decreased the total length of gastric erosion, venular deposits of Monastral blue B, and rolling of leucocytes in venules, and relatively increased luminol-dependent chemiluminescence activity generated by zymosan-stimulated leucocytes 15 min after thermal injury. These results suggest that serine proteases are involved in the formation of gastric erosions and gastric microcirculatory disturbance in the early period after thermal injury.     

Differing time courses between Δlactate and mitochondrial respiration during coronary occlusion and after reperfusion in canine hearts

Summary The present study was designed to clarify whether or not a difference between arterial and venous lactate (lactate) levels is useful for evaluation of mitochondrial function in ischemia-reperfused myocardium. In the first experiment, 12 dogs were divided into 2 groups: 10-min occlusion of the left anterior descending coronary artery (LAD) followed by 10-min reperfusion, or 30-min occlusion followed by 40-min reperfusion, were performed. The lactate levels in the femoral artery and the great cardiac vein were measured enzymatically. Lactate was reversed immediately after occlusion. Ten min and 20 min were required for the recovery of lactate in the 10-min-occlusion with 10-min-reperfusion, and 30-min-occlusion with 40-min-reperfusion groups, respectively. In the second experiment, 36 dogs were divided into 6 groups: 10-min occlusion of LAD; 10-min occlusion with 10-min reperfusion; 30-min occlusion; and 30-min occlusion with 10-, 20-, or 40-min reperfusion were performed. Mitochondria from normal and occluded or reperfused areas were prepared, and the respiratory function of the mitochondria was measured polarographically. No significant decreases in the mitochondrial function were observed in the 10-min-occlusion, and 10-min-occlusion with 10-min-reperfusion groups. On the other hand, respiratory function of mitochondria was impaired by 30-min occlusion and was not improved by 10- or 20-min reperfusion. Significant recovery in the mitochondrial function was observed after 40-min reperfusion. That is, differing recovery time courses between lactate and the mitochondrial function were observed.