Human recombinant erythropoietin improves motor function in rats with spinal cord compression-induced cervical myelopathy.

OBJECTIVE: Erythropoietin (EPO) is a clinically available hematopoietic cytokine. EPO has shown beneficial effects in the context of spinal cord injury and other neurological conditions. The aim of this study was to evaluate the effect of EPO on a rat model of spinal cord compression-induced cervical myelopathy and to explore the possibility of its use as a pharmacological treatment. METHODS: To develop the compression-induced cervical myelopathy model, an expandable polymer was implanted under the C5-C6 laminae of rats. EPO administration was started 8 weeks after implantation of a polymer. Motor function of rotarod performance and grip strength was measured after surgery, and motor neurons were evaluated with H-E, NeuN and choline acetyltransferase staining. Apoptotic cell death was assessed with TUNEL and Caspase-3 staining. The 5HT, GAP-43 and synaptophysin were evaluated to investigate the protection and plasticity of axons. Amyloid beta precursor protein (APP) was assessed to evaluate axonal injury. To assess transfer of EPO into spinal cord tissue, the EPO levels in spinal cord tissue were measured with an ELISA for each group after subcutaneous injection of EPO. RESULTS: High-dose EPO maintained motor function in the compression groups. EPO significantly prevented the loss of motor neurons and significantly decreased neuronal apoptotic cells. Expression of 5HT and synaptophysin was significantly preserved in the EPO group. APP expression was partly reduced in the EPO group. The EPO levels in spinal cord tissue were significantly higher in the high-dose EPO group than other groups. CONCLUSION: EPO improved motor function in rats with compression-induced cervical myelopathy. EPO suppressed neuronal cell apoptosis, protected motor neurons, and induced axonal protection and plasticity. The neuroprotective effects were produced following transfer of EPO into the spinal cord tissue. These findings suggest that EPO has high potential as a treatment for degenerative cervical myelopathy.

Autologous Transfusion of Blood Aspirated during Suction Decompression in Clipping of Large or Giant Cerebral Aneurysm.

The suction decompression (SD) method, which proactively aspirates the blood flowing into the aneurysm and reduces the internal pressure of the aneurysm, is useful for clipping surgery of large and giant cerebral aneurysm. However, there has been little discussion on re-utilization of blood aspirated during SD. This study aimed to examine the safety, convenience, and usefulness of autologous transfusion of aspirated blood using a transfusion bag. At the time of craniotomy, the cervical carotid artery is fully exposed. An angiocatheter sheath was inserted into the carotid artery and placed in the internal carotid artery. In SD, blood was aspirated from the sheath at a constant speed and quickly stored in a blood transfusion storage bag. Blood aspiration was repeated with a new syringe; once the transfusion bag was full, the blood was re-administered to the patient. Changes in vital sign and hemoglobin/hematocrit values before and after SD were examined in five cases performed in this procedure. The aspirated blood volumes of five cases ranged from 130 to 400 mL, and all aspirated blood was successfully re-transfused. There was no critical change in vital sign, and no significant decrease in the hemoglobin/hematocrit value. No findings suggestive of complications of thrombus formation, infection, and hemolysis were noted. Re-transfusion of aspirated blood during SD using a transfusion bag is a simple and safe method, which can minimize potential risk of re-utilizing aspirated blood, and enables the safe and easy execution of SD regardless of aspirated blood volume.

Transaminase Inhibition by 2-Hydroxyglutarate Impairs Glutamate Biosynthesis and Redox Homeostasis in Glioma.

IDH1 mutations are common in low-grade gliomas and secondary glioblastomas and cause overproduction of (R)-2HG. (R)-2HG modulates the activity of many enzymes, including some that are linked to transformation and some that are probably bystanders. Although prior work on (R)-2HG targets focused on 2OG-dependent dioxygenases, we found that (R)-2HG potently inhibits the 2OG-dependent transaminases BCAT1 and BCAT2, likely as a bystander effect, thereby decreasing glutamate levels and increasing dependence on glutaminase for the biosynthesis of glutamate and one of its products, glutathione. Inhibiting glutaminase specifically sensitized IDH mutant glioma cells to oxidative stress in vitro and to radiation in vitro and in vivo. These findings highlight the complementary roles for BCATs and glutaminase in glutamate biosynthesis, explain the sensitivity of IDH mutant cells to glutaminase inhibitors, and suggest a strategy for maximizing the effectiveness of such inhibitors against IDH mutant gliomas.