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AbstractA pulse sequence was implemented to observe the magnetization transfer (MT) effect on metabolites, water, and macromolecules in human frontal lobes in vivo at 1.5 Tesla. Signals were compared following the application of three hard pulses of 0.745 μT amplitude, applied at frequency offsets of either 2500 Hz or 30 kHz, preceding a conventional point‐resolved spectroscopy (PRESS)‐localized acquisition with an echo time (TE) of 30 ms and repetition time (TR) of 3 s. This gave an MT effect on water in vivo of 46%, while direct saturation by the MT pulses at 2.5 kHz offset was confirmed to be under 4% for all metabolites. We observed significant MT saturation in vivo for N‐acetylated compounds, choline (Cho), myo‐inositol, and lactate (Lac); a trend of an effect on glutamate + glutamine (Glx); and the typically observed effect on creatine (Cr). No significant MT effect was seen on the macromolecule signal, which was observed using metabolite nulling. Magn Reson Med, 2005. © 2005 Wiley‐Liss, Inc.

Neuroimaging studies have demonstrated gray matter (GM) volume abnormalities in substance users. While the majority of substance users are polysubstance users, very little is known about the relation between GM volume abnormalities and polysubstance use.In this study we assessed the relation between GM volume, and the use of alcohol, tobacco, cocaine and cannabis as well as the total number of substances used, in a sample of 169 males: 15 non-substance users, 89 moderate drinkers, 27 moderate drinkers who also smoke tobacco, 13 moderate drinkers who also smoke tobacco and use cocaine, 10 heavy drinkers who smoke tobacco and use cocaine and 15 heavy drinkers who smoke tobacco, cannabis and use cocaine.Regression analyses showed that there was a negative relation between the number of substances used and volume of the dorsal medial prefrontal cortex (mPFC) and the ventral mPFC. Without controlling for the use of other substances, the volume of the dorsal mPFC was negatively associated with the use of alcohol, tobacco, and cocaine. After controlling for the use of other substances, a negative relation was found between tobacco and cocaine and volume of the thalami and ventrolateral PFC, respectively.These findings indicate that mPFC alterations may not be substance-specific, but rather related to the number of substances used, whereas, thalamic and ventrolateral PFC pathology is specifically associated with tobacco and cocaine use, respectively. These findings are important, as the differential alterations in GM volume may underlie different cognitive deficits associated with substance use disorders.

We present a protocol for the biosensor Cell-Fit-HD4D. It enables long-term monitoring and correlation of single-cell fate with subcellular-deposited energy of ionizing radiation. Cell fate tracking using widefield time-lapse microscopy is uncoupled in time from confocal ion track imaging. Registration of both image acquisition steps allows precise ion track assignment to cells and correlation with cellular readouts. For complete details on the use and execution of this protocol, please refer to Niklas et al. (2022).

While the harmful effects of alcohol abuse are well documented, experimental and clinical data support a potential benefit of light to moderate alcohol consumption. Cross-sectional studies have suggested an association between alcohol consumption and multiple sclerosis (MS) disability. In the absence of prospective, longitudinal studies, the causal nature of this relationship cannot be established. It remains possible that patients with increased disability progression reduce their alcohol intake. Even though there is substantial evidence for anti-inflammatory effects of low-to-moderate doses of alcohol, the associations need to be interpreted very cautiously. This study discusses the current state of knowledge about MS and alcohol consumption, and the limitations in conducting research with retrospective data in patients with MS.

Chronic ethanol exposure causes neurotoxicity and long-term learning and memory impairment along with hippocampal and frontal cortical dysfunction. Flavonoids possess antioxidant and anti-inflammatory properties believed to be contributory factors in reversing cognitive decline. 6-Methoxyflavone (6-MOF), a flavonoid occurring naturally in medicinal plants, has been reported to instigate neuroprotection by reversing cisplatin-induced hyperalgesia and allodynia. Consequently, this study was designed to investigate 6-MOF activity in models of chronic ethanol-induced cognitive impairment along with neurochemical correlates.Mice were given ethanol orally (2.0 g/kg daily) for 24 days plus either saline, 6-MOF (25-75mg/kg) or donepezil (4mg/kg) and then ethanol was withdrawn for the next 6 days. Animals were subsequently assessed for their cognitive performance in several models on days 1, 12, and 24, during abstinence (Day-26) and on the 7th day of the washout period. Following behavioral assessment, post-mortem dopamine, noradrenaline and vitamin C concentrations were quantified in the frontal cortex, hippocampus and striatum, using HPLC with UV detection.Chronic ethanol treatment suppressed locomotor activity and impaired cognitive tasks, which included novel object recognition, performance in the Morris water maze as well as the Y-maze, socialization and nest-building behavior throughout the protocol and during withdrawal. These behavioral deficits were at least partially restored by the co-administration of 6-MOF or donepezil with ethanol as were ethanol-induced deficits in frontal cortical and hippocampal dopamine plus noradrenaline, together with striatal dopamine. 6-MOF co-administration with ethanol also modestly restored striatal vitamin C levels.It is postulated that, apart from donepezil, 6-MOF may be useful not only in the treatment of ethanol withdrawal severity but also in the management of chronic ethanol withdrawal induced cognitive impairment.

Activity pacing (AP) is a concept that is central to many chronic pain theories and treatments, yet there remains confusion regarding its definition and effects.To review the current knowledge concerning AP and integrate this knowledge in a manner that allows for a clear definition and useful directions for future research.A narrative review of the major theoretical approaches to AP and of the empirical evidence regarding the effects of AP interventions, followed by an integrative discussion.The concept of AP is derived from 2 main traditions: operant and energy conservation. Although there are common elements across these traditions, significant conceptual and practical differences exist, which has led to confusion. Little empirical evidence exists concerning the efficacy of AP as a treatment for chronic pain.Future research on AP should be based on a clear theoretical foundation, consider the context in which the AP behavior occurs and the type of pacing problem ("underactivity" vs. "overactivity"), and should examine the impact of AP treatment on multiple clinical outcomes. We provide a provisional definition of AP and specific recommendations that we believe will move the field forward.

Systemic delivery of therapeutic agents remains ineffective against diffuse intrinsic pontine glioma (DIPG), possibly due to an intact blood-brain-barrier (BBB) and to dose-limiting toxicity of systemic chemotherapeutic agents. Convection-enhanced delivery (CED) into the brainstem may provide an effective local delivery alternative for DIPG patients.The aim of this study is to develop a method to perform CED into the murine brainstem and to test this method using the chemotherapeutic agent carmustine (BiCNU). To this end, a newly designed murine CED catheter was tested in vitro and in vivo. After determination of safety and distribution, mice bearing VUMC-DIPG-3 and E98FM-DIPG brainstem tumors were treated with carmustine dissolved in DW 5% or carmustine dissolved in 10% ethanol.Our results show that CED into the murine brainstem is feasible and well tolerated by mice with and without brainstem tumors. CED of carmustine dissolved in 5% DW increased median survival of mice with VUMC-DIPG-3 and E98FM-DIPG tumors with 35% and 25% respectively. Dissolving carmustine in 10% ethanol further improved survival to 45% in mice with E98FM-DIPG tumors.Since genetically engineered and primary DIPG models are currently only available in mice, murine CED studies have clear advantages over CED studies in other animals.CED in the murine brainstem can be performed safely, is well tolerated and can be used to study efficacy of chemotherapeutic agents orthotopically. These results set the foundation for more CED studies in murine DIPG models.