Idiopathic intracranial hypertension: 120-day clinical, radiological, and manometric outcomes after stent insertion into the dural venous sinus.

OBJECTIVE Idiopathic intracranial hypertension (IIH) is commonly associated with venous sinus stenosis. In recent years, transvenous dural venous sinus stent (DVSS) insertion has emerged as a potential therapy for resistant cases. However, there remains considerable uncertainty over the safety and efficacy of this procedure, in particular the incidence of intraprocedural and delayed complications and in the longevity of sinus patency, pressure gradient obliteration, and therapeutic clinical outcome. The aim of this study was to determine clinical, radiological, and manometric outcomes at 3-4 months after DVSS in this treated IIH cohort. METHODS Clinical, radiographic, and manometric data before and 3-4 months after DVSS were reviewed in this single-center case series. All venographic and manometric procedures were performed under local anesthesia with the patient supine. RESULTS Forty-one patients underwent DVSS venography/manometry within 120 days. Sinus pressure reduction of between 11 and 15 mm Hg was achieved 3-4 months after DVSS compared with pre-stent baseline, regardless of whether the procedure was primary or secondary (after shunt surgery). Radiographic obliteration of anatomical stenosis correlating with reduction in pressure gradients was observed. The complication rate after DVSS was 4.9% and stent survival was 87.8% at 120 days. At least 20% of patients developed restenosis following DVSS and only 63.3% demonstrated an improvement or resolution of papilledema. CONCLUSIONS Reduced venous sinus pressures were observed at 120 days after the procedure. DVSS showed lower complication rates than shunts, but the clinical outcome data were less convincing. To definitively compare the outcomes between DVSS and shunts in IIH, a randomized prospective study is needed.

Selective binding of nuclear alpha-synuclein to the PGC1alpha promoter under conditions of oxidative stress may contribute to losses in mitochondrial function: implications for Parkinson's disease.

Alpha-synuclein has been reported to be present in the nucleus and levels enhanced by oxidative stress. Herein, we sought to investigate the mechanistic role of nuclear alpha-synuclein. We found that alpha-synuclein nuclear localization coincided with enhanced chromatin binding both in an in vitro and a corresponding in vivo brain oxidative stress model previously characterized by our laboratory as well as in PD brain tissues. Genome-wide chromatin immunoprecipitation (ChIP)-on-chip analysis of alpha-synuclein:promoter binding in response to oxidative stress in vitro revealed that binding occurs at several promoters belonging to a range of functional categories including transcriptional regulation. Interestingly, given the important role of mitochondrial dysfunction in PD, this included binding to the promoter for the master mitochondrial transcription activator, PGC1alpha in vitro, in vivo, and in human brain tissue with age and PD. To test the possible mechanistic impact of alpha-synuclein PGC1alpha promotor binding, we assessed PGC1alpha promoter activity, mRNA, and protein levels and expression of candidate PGC1alpha target genes in our in vitro model. All were found to be reduced in conjunction with increased levels of aberrant mitochondrial morphology and impaired mitochondrial function. Exogenous PGC1alpha expression was found to attenuate alpha-synuclein-mediated mitochondrial dysfunction and subsequent neurotoxicity in vitro. Our data suggest that nuclear alpha-synuclein localization under conditions of oxidative stress may impact on mitochondrial function in part via the protein's capacity to act as a transcriptional modulator of PGC1alpha. This represents a novel role for alpha-synuclein as it relates to mitochondrial dysfunction in PD.

Mao-B elevation decreases parkin's ability to efficiently clear damaged mitochondria: protective effects of rapamycin.

Increased oxidative stress in the Parkinsonian substantia nigra is believed to contribute to neurodegeneration, in part due to regionally elevated levels of the enzyme monoamine oxidase B (MAO-B). Increased oxidative stress has also been reported to be associated with the inhibition of E3 ligase activity of the Parkinson's disease-related protein parkin. In an inducible MAO-B cell model, losses in parkin E3 ligase activity were found to occur in conjunction with reduced mitochondrial turnover and decreased mitochondrial function, although this did not inhibit parkin's ability to translocation to damaged mitochondria. The mTOR inhibitor rapamycin was found to restore both mitophagy and mitochondrial function in these cells. These data suggest that MAO-B induction can interfere with mitochondrial quality control via losses in parkin activity that in turn impact on mitochondrial turnover. Rapamycin may be an effective means of counteracting the effects of lost parkin function by independently enhancing autophagic removal of damaged mitochondria.

Pneumorrhachis, pneumomediastinum, pneumopericardium and subcutaneous emphysema as complications of bronchial asthma.

Pneumorrhachis (PR), or epidural emphysema, denotes the presence of air in the spinal epidural space. It can be associated with a variety of etiologies, including trauma; recent iatrogenic manipulations during surgical, anesthesiological and diagnostic interventions; malignancy and its associated therapy. It usually represents an asymptomatic epiphenomenon but also can be symptomatic by itself as well as by its underlying pathology. The pathogenesis and etiology of PR are varied and can sometimes be a diagnostic challenge. As such, there are no standard guidelines for the management of symptomatic PR, and its treatment is often individualized. Frequently, multidisciplinary approach and regimes are required for its management. PR associated with bronchial asthma is extremely rare, and only very few cases are reported in the literature. Here, we report a case of a 17-year-old Saudi male patient who is a known case of bronchial asthma; he presented with extensive subcutaneous emphysema, pneumomediastinum, pneumopericardium and pneumorrhachis as complications of an acute exacerbation of his primary ailment.

Protective effect of adenosine in rat model of Parkinson's disease: neurobehavioral and neurochemical evidences.

Normal cellular metabolism produces oxidants which are neutralized within the cell by antioxidant enzymes and other antioxidants. An imbalance between oxidant and antioxidant has been postulated to lead the degeneration of dopaminergic neurons in Parkinson's disease. In this study, we examined whether adenosine, an antioxidant, can prevent or slowdown neuronal injury in 6-hydroxydopamine (6-OHDA) model of Parkinsonism. Rats were treated with adenosine (500, 250, 125 mg/kg b.wt.) once before surgery and five times after surgery (1 h interval). 2 microl 6-OHDA (12.5 microg in 0.2% ascorbic acid in normal saline) was infused in the right striatum. Two weeks after 6-OHDA infused rats were tested for neurobehavioral activity and sacrificed after 3 weeks of 6-OHDA infusion, for the estimation of glutathione peroxidase, glutathione-S-transferase, glutathione reductase, glutathione content, lipid peroxidation and dopamine and its metabolites. Adenosine was found to be successful in up-regulating the antioxidant status, lowering the dopamine loss and functional recovery returned close to the baseline dose. This study revealed that adenosine, which is an essential part of our body, might be helpful in slowing down the progression of neurodegeneration in Parkinsonism.

Tellurium-induced dose-dependent impairment of antioxidant status: differential effects in cerebrum, cerebellum, and brainstem of mice.

The effect of various doses of sodium tellurite (0.4, 0.8, and 2.0 mg/kg body weight, orally) on the activity of antioxidant enzymes (glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and catalase) and content of glutathione and thiobarbituric acid reactive substances (TBARSs) in the cerebrum, cerebellum, and brainstem of male albino mice was studied after 15 d of treatment. All of the doses of tellurium (0.4, 0.8, and 2.0 mg/kg body weight, orally) have depleted the activity of antioxidant enzymes and the content of glutathione dose dependently in the cerebrum, cerebellum, and brainstem and it was significant with the dose of 2.0 mg/kg. On the other hand, the 2.0-mg/kg dose of tellurium has significantly elevated the content of TBARSs in the cerebrum and cerebellum. The 0.8-mg/kg dose of tellurium has significantly depleted the activities of glutathione peroxidase in the cerebrum and brainstem, glutathione-Stransferase in the cerebrum and cerebellum, catalase in the brainstem, and the content of glutathione in the cerebrum and cerebellum. In contrast, this dose has significantly elevated the content of TBARSs in the cerebrum and cerebellum. However, the depletion in the activity of glutathione reductase with various doses of sodium tellurite was not significant in any brain part of mice. The result suggests that sodium tellurite differentially affects the antioxidant status within various parts of the mice brain.

Dose-dependent protective effect of selenium in rat model of Parkinson's disease: neurobehavioral and neurochemical evidences.

Normal cellular metabolism produces oxidants that are neutralized within cells by antioxidant enzymes and other antioxidants. An imbalance between oxidant and antioxidant has been postulated to lead the degeneration of dopaminergic neurons in Parkinson's disease. In this study, we examined whether selenium, an antioxidant, can prevent or slowdown neuronal injury in a 6-hydroxydopamine (6-OHDA) model of Parkinsonism. Rats were pre-treated with sodium selenite (0.1, 0.2 and 0.3 mg/kg body weight) for 7 days. On day 8, 2 micro L 6-OHDA (12.5 micro g in 0.2% ascorbic acid in normal saline) was infused in the right striatum. Two weeks after 6-OHDA infusion, rats were tested for neurobehavioral activity, and were killed after 3 weeks of 6-OHDA infusion for the estimation of glutathione peroxidase, glutathione-S-transferase, glutathione reductase, glutathione content, lipid peroxidation, and dopamine and its metabolites. Selenium was found to be successful in upregulating the antioxidant status and lowering the dopamine loss, and functional recovery returned close to the baseline dose-dependently. This study revealed that selenium, which is an essential part of our diet, may be helpful in slowing down the progression of neurodegeneration in parkinsonism.