Quantitative Thermal Stimulation Using Therapeutic Ultrasound to Improve Cerebral Blood Flow and Reduce Vascular Stiffness.

It is important to improve cerebrovascular health before the occurrence of cerebrovascular disease, as it has various aftereffects and a high recurrence rate, even with appropriate treatment. Various medical recommendations for preventing cerebrovascular diseases have been introduced, including smoking cessation, exercise, and diet. However, the effectiveness of these methods varies greatly from person to person, and their effects cannot be confirmed unless they are practiced over a long period. Therefore, there is a growing need to develop more quantitative methods that are applicable to the public to promote cerebrovascular health. Thus, in this study, we aimed to develop noninvasive and quantitative thermal stimulation techniques using ultrasound to improve cerebrovascular health and prevent cerebrovascular diseases. This study included 27 healthy adults in their 20s (14 males, 13 females). Thermal stimulation using therapeutic ultrasound at a frequency of 3 MHz was applied to the right sternocleidomastoid muscle in the supine posture for 2 min at four intensities (2.4, 5.1, 7.2, and 10.2 W/cm2). Diagnostic ultrasound was used to measure the peak systolic velocity (PSV), heart rate (HR), and pulse wave velocity (PWV) in the right common carotid artery (CCA), and the physiological changes were compared between intervention intensities. Compared to pre-intervention (preI), the PSV showed a significant increase during intervention (durI) at intensities of 7.2 W/cm2 and 10.2 W/cm2 (p = 0.010 and p = 0.021, respectively). Additionally, PWV showed a significant decrease for post-intervention (postI) at 7.2 W/cm2 and 10.2 W/cm2 (p = 0.036 and p = 0.035, respectively). However, the HR showed no significant differences at any of the intensities. The results demonstrate that an intervention at 3 MHz with an intensity of 7.2 W/cm2 or more can substantially increase cerebral blood flow and reduce arterial stiffness. Therefore, the use of therapeutic ultrasound of appropriate intensity is expected to improve the cerebral blood flow and reduce vascular stiffness to maintain cerebral blood flow at a certain level, which is closely related to the prevention and treatment of cerebrovascular diseases, thereby improving cerebrovascular health.

The erythropoietin-derived peptide MK-X and erythropoietin have neuroprotective effects against ischemic brain damage.

Erythropoietin (EPO) has been well known as a hematopoietic cytokine over the past decades. However, recent reports have demonstrated that EPO plays a neuroprotective role in the central nervous system, and EPO has been considered as a therapeutic target in neurodegenerative diseases such as ischemic stroke. Despite the neuroprotective effect of EPO, clinical trials have shown its unexpected side effects, including undesirable proliferative effects such as erythropoiesis and tumor growth. Therefore, the development of EPO analogs that would confer neuroprotection without adverse effects has been attempted. In this study, we examined the potential of a novel EPO-based short peptide, MK-X, as a novel drug for stroke treatment in comparison with EPO. We found that MK-X administration with reperfusion dramatically reduced brain injury in an in vivo mouse model of ischemic stroke induced by middle cerebral artery occlusion, whereas EPO had little effect. Similar to EPO, MK-X efficiently ameliorated mitochondrial dysfunction followed by neuronal death caused by glutamate-induced oxidative stress in cultured neurons. Consistent with this effect, MK-X significantly decreased caspase-3 cleavage and nuclear translocation of apoptosis-inducing factor induced by glutamate. MK-X completely mimicked the effect of EPO on multiple activation of JAK2 and its downstream PI3K/AKT and ERK1/2 signaling pathways, and this signaling process was involved in the neuroprotective effect of MK-X. Furthermore, MK-X and EPO induced similar changes in the gene expression patterns under glutamate-induced excitotoxicity. Interestingly, the most significant difference between MK-X and EPO was that MK-X better penetrated into the brain across the brain-blood barrier than did EPO. In conclusion, we suggest that MK-X might be used as a novel drug for protection from brain injury caused by ischemic stroke, which penetrates into the brain faster in comparison with EPO, even though MK-X and EPO have similar protective effects against excitotoxicity.

Comparison of Imaging Selection Criteria for Intra-Arterial Thrombectomy in Acute Ischemic Stroke with Advanced CT.

OBJECTIVES: To compare two selection criteria (noncontrast CT [NCCT] with multi-phase CT Angiography [MPCTA] and CT perfusion [CTP]) for the determination of eligibility for thrombectomy. METHODS: We retrospectively enrolled 71 patients who underwent head NCCT, 9.6-cm CTP, and craniocervical single-phase CTA (SPCTA) within 6 hours of onset. The simulated MPCTA was reconstructed from 1-mm CTP images for assessment of collateral circulation. Infarct core (relative CBF < 30 %) and penumbra (Tmax > 6 seconds) volumes were measured. The infarct core < 70 mL with a mismatch ratio > 1.2 (CTP-A), infarct core ≤ 40 mL with a mismatch ratio > 1.8 (CTP-B), and ASPECTS > 5 with good collaterals (50 % ≥ MCA territory) were used to determine eligibility for thrombectomy. SPCTA was compared with the simulated MPCTA for assessment of collaterals. RESULTS: CTP-B determined that 11 patients were ineligible for thrombectomy, of which three were eligible by NCCT with MPCTA and 6 by CTP-A. CTP-A and CTP-B showed discrepancy in determining eligibility for thrombectomy between NCCT with MPCTA in three patients each, rendering no significant statistical difference (P > 0.05). The number of patients with poor collaterals was significantly higher on SPCTA than MPCTA (n = 22 and 6 respectively; P < 0.0001). CONCLUSION: The two imaging selection criteria (NCCT with MPCTA and CTP) were statistically comparable for determining eligibility for thrombectomy. KEY POINTS: • Early mechanical thrombectomy improves clinical outcomes. • Noncontrast CT-multi-phase CTA is used for determining eligibility for thrombectomy. • CTP can help to select patients who are eligible for thrombectomy. • Noncontrast CT-multi-phase CTA and CTP are comparable for patient selection. • Multi-phase CTA is more accurate than single-phase CTA for assessment of collaterals.

Evolution of abnormal eye movements in Wernicke's encephalopathy: correlation with serial MRI findings.

A 33-year-old woman with Wernicke's encephalopathy (WE) due to poor oral intake after allogeneic stem cell transplantation for acute myeloid leukemia showed a sequential development of bilateral gaze-evoked nystagmus (GEN), rightward gaze palsy, and upbeat nystagmus. Initial MRIs obtained when she had GEN only showed a lesion involving the medullary tegmentum, and follow-up MRIs revealed additional lesions in the pontine and midbrain tegmentum along with development of rightward gaze palsy, and finally bilateral medial thalamus lesions in association with upbeat nystagmus. The evolution of abnormal ocular motor findings and serial MRI changes in our patient with WE provide imaging evidence on relative vulnerability of the neural structures, and on the progression of lesions and ocular motor findings in thiamine deficiency.

Bio-printing of collagen and VEGF-releasing fibrin gel scaffolds for neural stem cell culture.

Time-released delivery of soluble growth factors (GFs) in engineered hydrogel tissue constructs promotes the migration and proliferation of embedded cells, which is an important factor for designing scaffolds that ultimately aim for neural tissue regeneration. We report a tissue engineering technique to print murine neural stem cells (C17.2), collagen hydrogel, and GF (vascular endothelial growth factor: VEGF)-releasing fibrin gel to construct an artificial neural tissue. We examined the morphological changes of the printed C17.2 cells embedded in the collagen and its migration toward the fibrin gel. The cells showed high viability (92.89+/-2.32%) after printing, which was equivalent to that of manually-plated cells. C17.2 cells printed within 1mm from the border of VEGF-releasing fibrin gel showed GF-induced changes in their morphology. The cells printed in this range also migrated toward the fibrin gel, with the total migration distance of 102.4+/-76.1microm over 3days. The cells in the control samples (fibrin without the VEGF or VEGF printed directly in collagen) neither proliferated nor migrated. The results demonstrated that bio-printing of VEGF-containing fibrin gel supported sustained release of the GF in the collagen scaffold. The presented method can be gainfully used in the development of three-dimensional (3D) artificial tissue assays and neural tissue regeneration applications.

Prognosis of ocular myasthenia in Korea: a retrospective multicenter analysis of 202 patients.

OBJECTIVES: The aims of this study were to obtain data on the frequency with which Korean patients with autoimmune myasthenia gravis (MG) present solely with ocular disturbances and progress to develop generalized disease and to identify the prognostic factors associated with secondary generalization. METHODS: We conducted a retrospective multicenter survey in which a total of 376 adult patients who were newly diagnosed with MG from 2000 through 2005 were reviewed for analysis. Patients with ocular MG at the time of symptom presentation (n=202, 53.7%) were divided into two subgroups according to their prognosis: the patients whose disease remained ocular throughout the follow-ups were placed in the OMG-R group, and the patients who progressed to develop generalized disease were placed in the OMG-G group. Clinical characteristics and laboratory findings were compared between the two subgroups. RESULTS: Secondary generalization developed in 47 (23.3%) of the 202 study subjects, mostly within the first 6 months after symptom presentation, while the disease remained ocular throughout the follow-up duration (median 11.8 months) in the remaining 155 patients (76.7%). AChR antibody, abnormal repetitive nerve stimulation tests (RNST) and thymoma were more frequently observed in the patients in the OMG-G group than in those in the OMG-R group (p<0.01 in all). In seropositive cases, the titers of AChR antibody were also significantly higher in the OMG-G group than in the OMG-R group (median, 3.8 nM vs. 6.4 nM; p<0.05). Cox proportional hazards regression analyses showed that early oral prednisolone treatment significantly reduced the risk of secondary generalization (HR, 0.24; 95% CI, 0.11-0.56), whereas abnormal AChR antibody (HR, 5.34; 95% CI, 1.60-17.8) and thymoma (HR, 2.32; 95% CI, 1.21-4.45) were predictive of the development of secondary generalization. CONCLUSIONS: Our findings suggest that several factors, including the AChR antibody, thymoma, early corticosteroid treatment, and possibly latent neuromuscular abnormality revealed by RNST, may have an impact on the risk of developing generalized disease in Korean patients presenting with ocular myasthenia.