Altered expression of sphingosine kinase 1 and sphingosine-1-phosphate receptor 1 in mouse hippocampus after kainic acid treatment.

Kainic acid (KA) induces hippocampal cell death and astrocyte proliferation. There are reports that sphingosine kinase (SPHK)1 and sphingosine-1- phosphate (S1P) receptor 1 (S1P(1)) signaling axis controls astrocyte proliferation. Here we examined the temporal changes of SPHK1/S1P(1) in mouse hippocampus during KA-induced hippocampal cell death. Mice were killed at 2, 6, 24, or 48 h after KA (30 mg/kg) injection. There was an increase in Fluoro-Jade B-positive cells in the hippocampus of KA-treated mice with temporal changes of glial fibrillary acidic protein (GFAP) expression. The lowest level of SPHK1 protein expression was found 2h after KA treatment. Six hours after KA treatment, the expression of SPHK1 and S1P(1) proteins steadily increased in the hippocampus. In immunohistochemical analysis, SPHK1 and S1P(1) are more immunoreactive in astrocytes within the hippocampus of KA-treated mice than in hippocampus of control mice. These results indicate that SPHK1/S1P(1) signaling axis may play an important role in astrocytes proliferation during KA-induced excitotoxicity.

Percutaneous sacroplasty using CT guidance for pain palliation in sacral insufficiency fractures.

BACKGROUND AND OBJECTIVE: Sacroplasty has emerged as a treatment option for patients with painful osteoporotic sacral insufficiency fractures. We report short-term outcomes in a consecutive cohort of patients treated with sacroplasty. METHODS: We retrospectively reviewed 57 patients treated with sacroplasty for painful osteoporotic sacral fractures at our institution between 2004 and 2011. An 11-point numerical rating scale pain score was recorded at rest and at activity pre- and post-procedure. Opioids prescribed to the patient both pre- and post-procedure were recorded. RESULTS: Mean duration of pain prior to sacroplasty was 3 weeks (IQR 2-5). Procedural complications were minimal. Median post-procedure follow-up time was 2.5 weeks (IQR 1-5) among 45 patients with available data. Thirty-seven (82%) of the 45 patients experienced a numerical or descriptive decrease from initial pain at follow-up. Median activity pain scores collected from 13 patients decreased from 10 (IQR 8.5-10) pre-procedure to 6 (IQR 4-6.8) post-procedure (p<0.0001), and median rest pain scores collected from 29 patients decreased from 7 (IQR 4-8.5) to 2 (IQR 1-3.5)(p<0.0001). Twenty-two (76%) of 29 patients had at least a 30% decrease in rest pain scores. The median number of opioids prescribed per patient decreased from 1 (IQR 1-2) pre-procedure to 0 (IQR 0-1) post-procedure (p<0.0001). Thirty-four of 57 patients (60%) had decreased opioid usage, 15 (26%) patients had unchanged usage and 8 (14%) had increased usage. CONCLUSIONS: Our series demonstrates that sacroplasty is a safe and effective treatment in patients with painful osteoporotic insufficiency fractures.

Cervical Myelopathy Secondary to Atlanto-occipital Assimilation: The Usefulness of the Simple Decompressive Surgery.

Atlanto-occipital assimilation is one of the most common osseous anomalies observed at the craniocervical junction. Most patients with atlas assimilation show no symptom, but some have neurological problems such as myelopathy that may require surgical treatment. Occipitocervical fusion may be required if atlato-occipital assimilation is accompanied by occipito-axial instability. However, in cases of symptomatic atlas assimilation with minor cord compression without instability, simple decompressive surgery may be the treatment modality. This report describes a case of successful treatment of a patient with myelopathy secondary to atlanto-occipital assimilation without instability, using posterior simple decompressive surgery.

Caffeine inhibits cell proliferation and regulates PKA/GSK3ß pathways in U87MG human glioma cells.

Caffeine is the most commonly ingested methylxanthine and has anti-cancer effects in several types of cancer. In this study, we examined the anti-cancer effects of caffeine on gliomas, both in vitro and in vivo. In vitro, caffeine treatment reduced glioma cell proliferation through G(0)/G(1)-phase cell cycle arrest by suppressing Rb phosphorylation. In addition, caffeine induced apoptosis through caspase-3 activation and poly(ADP-ribose) polymerase (PARP) cleavage. Caffeine also phosphorylated serine 9 of glycogen synthase kinase 3 beta (GSK3ß). Pretreatment with H89, a pharmacological inhibitor of protein kinase A (PKA), was able to antagonize caffeine-induced GSK3ß(ser9) phosphorylation, suggesting that the mechanism might involve a cAMP-dependent PKA-dependent pathway. In vivo, caffeine-treated tumors exhibited reduced proliferation and increased apoptosis compared with vehicle-treated tumors. These results suggest that caffeine induces cell cycle arrest and caspase-dependent cell death in glioma cells, supporting its potential use in chemotherapeutic options for malignant gliomas.

Negative effect of hypopituitarism following brain trauma in patients with diffuse axonal injury.

OBJECT: The aim of this prospective observational study was to assess the incidence and pattern of hypopituitarism after diffuse axonal injury (DAI) and to identify its effect on these patients in terms of functional outcome. METHODS: Of 1307 patients with traumatic brain injury treated at the authors' institution between March 2005 and June 2008, 65 patients with DAI were enrolled in the present study. The authors determined basal hormone levels, initial Glasgow Coma Scale scores, the Marshall CT grades, the presence of abnormal signal intensity indicating lesions on MR images, and duration of unconsciousness. At the 6-month follow-up visits, functional outcomes were estimated using the Modified Barthel Index. Univariate and multivariate analyses were performed to identify factors that influenced functional outcomes. RESULTS: Twenty-one patients with hypopituitarism (Group A) had more lesions in the body of the corpus callosum, basal ganglia, thalamus, and the gray-white matter junction than those without hypopituitarism (Group B). In Group A, growth hormone deficiency (17 patients, 80.9%) was the most common, and multiple pituitary hormone deficiencies were found in 12 patients (57.1%). The mean Modified Barthel Index score at the 6-month follow-up was 64.7 in Group A and 88.5 in Group B (p = 0.027). Duration of unconsciousness (p = 0.035), the Marshall CT grade (p = 0.021), hypopituitarism (p = 0.044), and abnormal signal intensities on MR imaging in midline or deep structures of the brain (p = 0.001) were found to be associated with functional outcome. CONCLUSIONS: The findings in this prospective observational study suggest that hypopituitarism in patients with DAI has a relationship not only with injuries in the midline or deep structures of the brain, but also with a poor outcome.

Ethanol down regulates the expression of myelin proteolipid protein in the rat hippocampus.

It is well known that chronic ethanol treatment affects the synthesis of RNA and protein in the brain and the maintenance and function of nervous system. The changes in myelination-related genes are most prominent in human alcoholics. Previously, our cDNA microarray study showed altered Proteolipid protein (PLP), a major protein of central myelin. The present study aimed to gain more understanding of the expression of PLP after chronic ethanol treatment. Male Sprague-Dawley rats were daily treated with ethanol (15% in saline, 3 g/kg, i.p.) or saline for 14 days. Messenger RNAs from hippocampus of each group were subjected to cDNA expression array hybridization to determine the differential gene expressions. Among many ethanol responsive genes, PLP was negatively regulated by ethanol treatment, which is one of the most abundant proteins in the CNS and has an important role in the stabilization of myelin sheath. Using northern blot and immunohistochemical analysis, we showed the change in expression level of PLP mRNA and protein after ethanol treatment. PLP mRNA and protein were decreased in hippocampus of rat with chronic ethanol exposure, suggesting that ethanol may affect the stabilization of myelin sheath through the modulation of PLP expression and induce the pathophysiology of alcoholic brain.

Phosphorylation of 14-3-3ζ at serine 58 and neurodegeneration following kainic acid-induced excitotoxicity.

Oxidative stress-induced cell death leads to phosphorylation of 14-3-3ζ at serine 58. 14-3-3ζ is detected at significant levels in cerebrospinal fluid after kainic acid (KA)-induced seizures. Here we examined temporal changes in 14-3-3ζ phosphorylation in the hippocampus and amygdala of mice after KA treatment. Mice were killed at 2, 6, 24, or 48 h after KA (30 mg/kg) injection. We observed an increase in TUNEL and Fluoro-Jade B (FJB)-stained neurons in the hippocampus and amygdala of KA-treated mice. Phospho (p)-14-3-3ζ and p-JNK expression was increased in the hippocampus 2 and 6 h after KA treatment, respectively. In immunohistochemical analysis, p-14-3-3ζ-positive cells were present in the CA3 region of the hippocampus and the central nucleus of amygdala (CeA) of KA-treated mice. Thus, phosphorylation of 14-3-3ζ at serine 58 may play an important role in KA-induced hippocampal and amygdaloid neuronal damage.

Superior orbital rim approach for anterior communicating artery aneurysms: a surgical series of 27 patients.

There are debatable claims in the optimal approach for clipping of the anterior communicating artery (AcomA) aneurysm. The authors invented the superior orbital rim approach (SORA) as an alternative and minimally invasive approach for the treatment of AcomA aneurysm. The authors reviewed retrospectively all the medical records of 27 patients of subarachnoid hemorrhage due to ruptured AcomA aneurysm. who were admitted to Kosin University Gospel Hospital for last 2 yr. Fourteen women (51.9%) and 13 men (48.1%) were from 29 to 79 yr in age. The mean aneurysm size was 6.2 mm ranging from 4 to 12 mm. A favorable Glasgow outcome scale (GOS) of 4 or 5 was achieved in 92.6%, a GOS score of 3 in 3.7%, and 1 death (GOS 1) occurred in 3.7% of the patients. During the follow-up between 4 and 28 months (mean, 17.5 months) after the surgery, the prognosis of the patients and the cosmetic results were favorable compared with conventional approach. We became to believe that it was an alternative, effective and minimally invasive approach to the surgical treatment of AcomA aneurysm.