Propofol protects against blood-spinal cord barrier disruption induced by ischemia/reperfusion injury.

Propofol has been shown to exert neuroprotective effects on the injured spinal cord. However, the effect of propofol on the blood-spinal cord barrier (BSCB) after ischemia/reperfusion injury (IRI) is poorly understood. Therefore, we investigated whether propofol could maintain the integrity of the BSCB. Spinal cord IRI (SCIRI) was induced in rabbits by infrarenal aortic occlusion for 30 minutes. Propofol, 30 mg/kg, was intravenously infused 10 minutes before aortic clamping as well as at the onset of reperfusion. Then, 48 hours later, we performed histological and mRNA/protein analyses of the spinal cord. Propofol decreased histological damage to the spinal cord, attenuated the reduction in BSCB permeability, downregulated the mRNA and protein expression levels of matrix metalloprotease-9 (MMP-9) and nuclear factor-κB (NF-κB), and upregulated the protein expression levels of occludin and claudin-5. Our findings suggest that propofol helps maintain BSCB integrity after SCIRI by reducing MMP-9 expression, by inhibiting the NF-κB signaling pathway, and by maintaining expression of tight junction proteins.

Function of SOD1, SOD2, and PI3K/AKT signaling pathways in the protection of propofol on spinal cord ischemic reperfusion injury in a rabbit model.

AIMS: To verify that co-application of propofol preconditioning and postconditioning protects spinal cord from ischemia/reperfusion injury by enhancing the different subtypes of SOD activity, which is related to PI3K/AKT signal pathway. MATERIALS AND METHODS: 60 rabbits were randomly equally assigned to 3 groups: Group S, sham-operation group; Group I/R., ischemia/reperfusion group; Group P, ischemia/reperfusion group with propofol treatment. Four rabbits per group were randomly executed at the time-points: days 1, 2, 3, 5, and 7 post-surgery. Spinal cord tissues at L3 to L4 levels were harvested. The bioactivities of SOD1 and SOD2, and the mRNA expression levels of SOD1, SOD2, PI3K, and AKT were detected. KEY FINDINGS: On day 1, the bioactivity of SOD1 increased significantly in Group I/R or Group P compared with Group S (P<0.05). On day 2, compared with Group S, the bioactivity of SOD1 increased significantly in Group P (P<0.05). On days 3, 5, and 7, the bioactivity of SOD1 decreased significantly respectively in Group I/R compared with Group S (P<0.05). On all timepoints, the bioactivity of SOD2 decreased significantly in Group I/R compared with Group S (P<0.05). There was a positive correlation between the SOD1 activity and the respective mRNA expression of SOD1, PI3K, and AKT. SIGNIFICANCE: Co-application of propofol preconditioning and postconditioning resulted in potent protective effects against spinal cord ischemia/reperfusion injury, which was associated with the increased expression of SOD1 in spinal cord tissues by activating PI3K/AKT signal pathway.

The influence of input and output modality on following instructions in working memory.

Following instructions is an important component of learning and has been shown to rely on working memory. This study examined the ability to follow instructions within working memory under varying input and output modalities. In Experiment 1, participants heard, read, or viewed demonstration of short sequences of instructions, and recalled either by oral repetition or physical enactment. There was a significant main effect of encoding, showing superior recall performance when instructions were demonstrated relative to spoken or written presentation. Experiment 2 examined whether recall is further improved when instructions are presented both in spoken and demonstrated form, relative to single modality presentation. The advantage for demonstration over spoken instructions was replicated, and dual input was superior to spoken instructions. However, dual input did not bring extra benefit compared to demonstration of instructions. We also observed a significant enacted-retrieval recall advantage. These findings suggest effects of both input and output modalities on the ability to remember and follow instructions in working memory. Outcomes substantially inform the underexplored but important new area of action-based working memory and its links to embodied cognition, with implications for pedagogic practice.

Rostral medial prefrontal dysfunctions and consummatory pleasure in schizophrenia: a meta-analysis of functional imaging studies.

A large number of imaging studies have examined the neural correlates of consummatory pleasure and anticipatory pleasure in schizophrenia, but the brain regions where schizophrenia patients consistently demonstrate dysfunctions remain unclear. We performed a series of meta-analyses on imaging studies to delineate the regions associated with consummatory and anticipatory pleasure dysfunctions in schizophrenia. Nineteen functional magnetic resonance imaging or positron emission tomography studies using whole brain analysis were identified through a literature search (PubMed and EBSCO; January 1990-February 2014). Activation likelihood estimation was performed using the GingerALE software. The clusters identified were obtained after controlling for the false discovery rate at p<0.05 and applying a minimum cluster size of 200 mm(3). It was found that schizophrenia patients exhibited decreased activation mainly in the rostral medial prefrontal cortex (rmPFC), the right parahippocampus/amygala, and other limbic regions (e.g., the subgenual anterior cingulate cortex, the putamen, and the medial globus pallidus) when consummating pleasure. Task instructions (feeling vs. stimuli) were differentially related to medial prefrontal dysfunction in schizophrenia. When patients anticipated pleasure, reduced activation in the left putamen was observed, despite the limited number of studies. Our findings suggest that the medial prefrontal cortex and limbic regions may play an important role in neural dysfunction underlying deficits in consummatory pleasure in schizophrenia.

Effects of ketamine on the balance of ions Ca2+, Mg2+, Cu2+ and Zn2+ in the ischemia-reperfusion affected spinal cord tissues in rabbits.

To test the effects of ketamine on metal ion balance in the spinal cord tissues after ischemic reperfusion (I/R), 24 white adult Japanese rabbits were randomly assigned to sham operation group, I/R group or ketamine-treated I/R group. Spinal cord injuries in I/R group and ketamine-treated I/R group were induced by aortic occlusions. Rabbits in ketamine-treated I/R group were intravenously infused 10 mg/kg ketamine twice: once at 10 min before aortic clamping and once at the onset of reperfusion. Post-operative neurological functions and concentrations of ions Ca2+, Mg2+, Cu2+ and Zn2+ in the spinal cord were assessed. Compared with the sham operation group, rabbits in the I/R group showed significantly worsened neurological functions as scored with the modified Tarlov criteria and altered concentrations of ions Ca2+, Mg2+, Cu2+ and Zn2+. These unfavorable changes were significantly reversed in the ketamine-treated I/R group, suggesting that the potent protective effects of ketamine against the I/R-induced spinal cord injuries may be due to its ability to maintain ion balance in the I/R affected tissues.

Protective effect of ketamine on ischemic spinal cord injury in rabbits.

We tested our hypothesis that a commonly used anesthetic, ketamine, may offer benefits to protect animals from spinal cord injury, using the ischemia/reperfusion (I/R) injury rabbit model in a randomized controlled study. We used 24 white adult Japanese rabbits from the animal facility at the Medical College of Wuhan University. The rabbits were randomly assigned to one of three groups, eight rabbits per group: group I, sham-operation group; group II, I/R group; group III, I/R with ketamine treatment group. Spinal cord ischemia was induced by infrarenal aortic cross-clamp for 45 min in group II and group III, and ketamine was intravenously infused at 10 mg/kg in 15 mL 0.9% sodium chloride at a speed of 1.5 mL/min to animals in group III, once at 10 min before aortic clamping and once at the onset of reperfusion. Postoperative neurological function, electromyography of rear limbs, histopathology, malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activity in the spinal cord were assessed in all animals. Compared with the control group I, group II showed significant I/R injury-induced changes in neurological function scores, histopathology, and electromyography (p < 0.01). However, group III with ketamine treatment significantly reversed the changes in all these parameters (p < 0.01). At the same time, the I/R-induced increase in MDA content observed in group II was also significantly reduced in group III (p < 0.01), and the I/R-induced decreases in SOD activity were also significantly prevented in group III (p < 0.01). After ketamine treatment, all parameters examined in group III were not significantly different from those obtained in group I. Ketamine showed potent protective effects against spinal cord I/R injury in the rabbit model and protected loss of antioxidant activity in spinal cord tissues.

Effect of repetitive ischemic preconditioning on spinal cord ischemia in a rabbit model.

A completely randomized controlled study based on a rabbit model was designed to study the effect of repetitive ischemic preconditioning (IPC) on a spinal cord ischemic reperfusion injury. Twenty four white adult Japanese rabbits were randomly assigned to one of the 3 groups (n = 8 per group): Group I: sham-operation group, Group II: ischemic reperfusion group, and, Group III: IPC group. Spinal cord ischemia was induced by infra-renal aortic cross-clamp for 45 min in Group II. Before 45 min ischemia, the rabbits in Group III underwent four cycles of IPC (5 min of ischemia followed by 5 min of reperfusion). Post-operative neurological function, electromyography (EMG) of rear limbs, and spinal cord histopathological changes were measured. The concentrations of calcium, magnesium, copper, and zinc in spinal cord were measured in the 7th day. The neurological function and histopathological changes in Group II were significantly different from those in Group I or Group III (P < 0.05 or 0.01). There was a more significant change of EMG in Group II than that in Group III (P < 0.05). The concentrations of calcium and copper in Group II were significantly higher (P < 0.05 or 0.01), but magnesium and zinc were significantly lower (P < 0.05) than those in Group I. Calcium and copper in Group II were significantly higher (P < 0.05), but zinc was significantly lower (P < 0.01) than those in Group III. In conclusion, repetitive IPC can protect rabbit spinal cord from ischemic reperfusion injury in a timely manner, which is associated with corrections of imbalance of calcium, magnesium, copper, and zinc in the ischemic region.