The role of folate metabolism-related gene polymorphisms in the development of meningiomas

Meningiomas are (usually) slow-growing benign tumors, and several factors have been implicated in their development. Increasing age, previous exposure to ionizing radiation, endogenous hormone status and history, hormone replacement therapy, genetic variants and polymorphisms are the main factors that have been proven or assumed to be involved in meningioma formation. The complex genetic background supporting the pathogenesis of meningiomas includes a large number of mutations and polymorphisms that might be actively involved in tumor development, progression and recurrence. The aim of this mini-review is to summarize the current data concerning the role of folate metabolism-related gene polymorphisms in the development of meningiomas

The neuroprotective role of l-cysteine towards the effects of short-term exposure to lanthanum on the adult rat brain antioxidant status and the activities of acetylcholinesterase, (Na+,K+)- and Mg 2+-ATPase

Lanthanum (La) is a rare earth element that is widely used for industrial, medical and agricultural purposes. Its neurotoxic effects are linked to its physical and chemical properties and its interaction with certain trace elements and membrane-bound enzymes. The aim of this study was to investigate the effects of short-term La-administration (as LaCl3, 53 mg/kg) on the adult rat whole brain total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), Na+,K+-ATPase and Mg 2+-ATPase, as well as the potential effect of the co-administration of the antioxidant l-cysteine (Cys, 7 mg/kg) on the above parameters. Twenty-eight male Wistar rats were divided into four groups: A (saline-treated control), B (La), C (Cys),and D (La and Cys). All rats were treated once daily with intraperitoneal injections of the tested compounds, for 1-week. Rats were sacrificed by decapitation and the above mentioned parameters were measured spectrophotometrically. Rats treated with La exhibited a significant reduction in brain TAS (-36%, P < 0.001, BvsA), that was partially limited by the co-administration of Cys (-13%, P < 0.01, DvsA), while Cys (group C) had no effect on TAS. The rat brain AChE activity was found significantly increased by both La (+23%, P < 0.001, BvsA) and Cys (+59%, P < 0.001, CvsA), while it was adjusted to control levels by the co-administration of La and Cys. The activity of rat brain Na+,K+-ATPase was significantly decreased by La-administration (-28%, P < 0.001, BvsA), while Cys supplementation could not reverse this decrease. The activity of Mg 2+-ATPase exhibited a slight but statistically significant reduction due to La (-8%, P < 0.01, BvsA), that was further reduced by Cys co-administration (-25%, P < 0.001, DvsA). The above findings suggest that La short-term in vivo administration causes a statistically significant decrease in the rat brain TAS and an increase in AChE activity. Both effects can be, partially or totally, reversed into control levels by Cys co-administration, which could thus be considered for future applications as a neuroprotective agent against chronic exposure to La. The activities of Na+,K +- and Mg2+-ATPase that were inhibited by La, could not be reversed by Cys co-administration. A role for the already reported concentration-dependent interaction of La with Ca-binding sites (such as Ca 2+-ATPase) might be considered for certain of the above phenomena. © 2008 Springer Science+Business Media, LLC

Effects of adult-onset streptozotocin-induced diabetes on the rat brain antioxidant status and the activities of acetylcholinesterase, (Na +,K+)- and Mg2+-ATPase: Modulation by L-cysteine

Uncontrolled diabetes is known to affect the nervous system. The aim of this study was to investigate the effect of the antioxidant L-cysteine (Cys) on the changes caused by adult-onset streptozotocin (STZ)-induced diabetes on the rat brain total antioxidant status (TAS) and the activities of acetylcholinesterase (AChE), (Na+,K+)-ATPase and Mg 2+-ATPase. Thirty-eight male Wistar rats were divided into six groups: CA (8-week-control), CB (8-week-control + 1-week-saline-treated), C + Cys (8-week-control + 1-week-Cys-treated), D A (8-week-diabetic), DB (8-week-diabetic + 1-week-saline-treated) and D + Cys (8-week-diabetic + 1-week-Cys-treated). All diabetic rats were once treated with an intraperitoneal (i.p.) STZ injection (50 mg/kg body weight) at the beginning of the experiment, while all Cys-treated groups received i.p. injections of Cys 7 mg/kg body weight (daily, for 1-week, during the 9th-week). Whole rat brain parameters were measured spectrophotometrically. In vitro incubation with 0.83 mM of Cys or 10 mM of STZ for 3 h was performed on brain homogenate samples from groups CB and DB, in order to study the enzymes' activities. Diabetic rats exhibited a statistically significant reduction in brain TAS (-28%, D A vs CA;-30%, DB vs CB) that was reversed after 1-week-Cys-administration into basal levels. Diabetes caused a significant increase in AChE activity (+27%, DA vs CA; +15%, DB vs CB), that was further enhanced by Cys-administration (+57%, D + Cys vs CB). The C + Cys group exhibited no significant difference compared to the CB group in TAS (+2%), but showed a significantly increased AChE activity (+66%, C + Cys vs C B). Diabetic rats exhibited a significant reduction in the activity of Na+,K+-ATPase (-36%, DA vs C A;-48%, DB vs CB) that was not reversed after 1-week Cys administration. However, in vitro incubation with Cys partially reversed the diabetes-induced Na+,K+-ATPase inhibition. Mg2+-ATPase activity was not affected by STZ-induced diabetes, while Cys caused a significant inhibition of the enzyme, both in vivo (-14%, C + Cys vs CB;-17%, D + Cys vs CB) and in vitro (-16%, D B + in vitro Cys vs CB). In vitro incubation with STZ had no effect on the studied enzymes. The present data revealed a protective role for Cys towards the oxidative effect of diabetes on the adult rat brain. Moreover, an increase in whole brain AChE activity due to diabetes was recorded (not repeatedly established in the literature, since contradictory findings exist), that was further increased by Cys. The inhibition of Na +,K+-ATPase reflects a possible mechanism through which untreated diabetes could affect neuronal excitability, metabolic energy production and certain systems of neurotransmission. As concerns the use of Cys as a neuroprotective agent against diabetes, our in vitro findings could be indicative of a possible protective role of Cys under different in vivo experimental conditions. © 2009 Springer Science+Business Media, LLC

A Neurological Wake-Up Test in the Neurointensive Care Unit: Pros and Cons

Traumatic brain injury (TBI) induces a marked systemic biochemical stress response with the release of several stress-related hormones including cortisol and the catecholamines. A major aim of using continuous sedation in the neurointensive care unit (NIC) unit is to attenuate the TBI-induced stress response via reduction of the cerebral energy metabolic demands. In the era of modern multimodality monitoring and neuroimaging for patients with severe TBI, what is the role for neurological evaluation, a neurological wake-up test (NWT), of patients on continuous sedation and mechanical ventilation? In particular, does the information obtained by the NWT outweigh the risk of inducing a substantial stress response? The additional use of NWTs in NIC is controversial and is not mentioned in any recent TBI guidelines. Although daily interruption of continuous sedation is suggested for patients in general intensive care, reasons for not using the NWT in NIC may be a fear of an NWT-induced stress response and uncertainty to the additional value of NWTs in patients monitored with multimodality monitoring and frequent neuroradiological examinations. A recent survey showed that use of NWT varies markedly in Scandinavians’ NIC units where half of the evaluated centres never use the NWT, whereas others use the NWT up to six times daily. In a series of studies characterising the NWT-induced stress response, the NWT was found to induce a significant increase in ICP and CPP in severe TBI patients on controlled ventilation. Additionally, the NWT caused an increase in adrenocorticotrophic (ACTH) hormone, catecholamine and cortisol levels. In the absolute majority of patients, the ICP and CPP changes were modest and transient and the absolute increases in stress hormone levels were small. However, the stress response was marked in a small subset of patients. These studies suggest that the NWT is safe in the majority of patients but that the test should be individualised and avoided in patients reacting with markedly increased ICP and/or decreased CPP. Although important clinical information may be obtained from the NWT, future studies need to evaluate the risk-benefit ratio of the NWT in TBI management