Hyperpolarized 1- 13Cpyruvate Magnetic Resonance Spectroscopy Shows That Agmatine Increased Lactate Production in the Brain of Type 2 Diabetic Mice

Purpose@#Type 2 diabetes mellitus (T2DM) is associated with a 2-fold increased risk of developing Alzheimer’s disease. In earlier research, agmatine has been demonstrated to alleviate diabetes symptoms and increase cognitive performance. However, it is unclear whether the improvement of cognitive function is attributable to the reduction of diabetic symptoms or its direct influence on brain metabolism. Using hyperpolarized (HP) [1- 13C]pyruvate magnetic resonance spectroscopy (MRS), this study intends to evaluate the influence of agmatine on brain metabolism. @*Materials and Methods@#ICR mice were fed a high-fat diet and injected with streptozotocin to develop a T2DM animal model. During a 2-week period, T2DM mice were treated with normal saline or 100 mg/kg of agmatine, and brain HP [1- 13C]pyruvate MRS was performed. The effect of agmatine on lactate generation and NADH/NAD+ redox state was investigated using C6 and neuro-2a (N2a) cells. @*Results@#As a perfusion marker, the total 13C signals in the brain of T2DM mice (p=0.07) and agmatine-treated mice (p<0.05) were reduced. The conversion constant (Kpl) from [1- 13C]pyruvate to [1- 13C]lactate was not distinguishable in the brains of T2DM mice but was significantly increased in the brains of agmatine-treated T2DM mice. Treating C6 and N2a cells with agmatine increased NADH/NAD+ ratio and lactate generation. @*Conclusion@#Agmatine influences the NADH/NAD+ redox state in the brains of T2DM mice, which may be connected with enhanced cognitive performance and increased conversion of HP [1- 13C]pyruvate to HP [1- 13C]lactate.

Effect of Cerebral Motor Cortex Stimulation in Amyotrophic Lateral Sclerosis Model: A Preliminary Controlled Study

OBJECTIVE: To observe the effect of the depolarizing stimulation in amyotrophic lateral sclerosis (ALS) mouse model on the survival and behavioral performance. METHOD: Transgenic male mouse model of ALS at the age of 9~11 weeks were divided into sham control group (n=10) and stimulation group (n=9). Electrode was implanted in the motor cortex in left hemisphere. Movement thresholds (MT) were regularly checked. Half threshold of MT, unipolar, and continuous electrical stimulation (frequency, 50 Hz; pulse duration, 220micron s) was delivered through implanted electrode. Behavioral tests including Rota-rod and Paw-grip endurance were checked every day. RESULTS: Induction of symptom was delayed in 8 days in stimulation than sham control group. However, there was no significant difference in survival in both groups. Behavioral tests showed that stimulation group is significantly better than sham group in Rota-rod (11~15 weeks) and in grip endurance (11~14, 16 weeks). MT was always between 1.0 volt and 3.2 volt in sham group, however, MT was between 0.8 volt and 2.8 volt in stimulation group. MT was jumped up around the time of death in both groups. CONCLUSION: Electrical stimulation is considered to be one of possible trial methods in ALS model. However, parameters of the stimulation in the experiment should be modified for better results.

Ultrasonographic Findings of Carpal Tunnel Syndrome in Patients with Paraplegia

OBJECTIVE: To assess the diagnostic value of ultrasonography for the median nerve, the state of life style activities and the pain degree of upper extremities in paraplegics with carpal tunnel syndrome (CTS). METHOD: Eighteen wheelchair ambulators with spinal cord injury who had neurological level below T2 were studied. Patients with peripheral or central neuropathies were excluded. Patients were assigned to either the electrodiagnostic CTS (group CTS, 7) or electrodiagnostically negative (group non- CTS, 11), and healthy volunteers (15) were classified as control group. The cross sectional area of the median nerve (MN-CSA) at carpal pisiform level was ultrasonographically measured. The degree of painful restriction to execute ADL by hands (TR-ADL), the pain grade (visual analog scale, VAS) of upper extremities and revised version of Korean spinal cord independence measure (KSCIM-R) for functional level were measured and analyzed. RESULTS: Nine hands (14.3%) of 7 patients out of 34 hands had CTS in electrodiagnostic study. There were significant difference among groups in TR-ADL hours (CTS group; 5.0 vs non-CTS group; 10.2, p0.05), MN-CSA (12.3 mm2 vs 7.9 mm2 vs control group; 8.0 mm2, p<0.05). Using the ROC curve, the cut-off value of MN-CSA produced 8.5 mm2 providing a diagnostic sensitivity of 77.8% and specificity of 59.6%. CONCLUSION: The ultrasonographic measurement of the median nerve may be a useful non-invasive screening test for the diagnosis of CTS in paraplegic patients with wrist pain.