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Brain Sci., Volume 8, Issue 3 (March 2018)

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Cover Story (view full-size image) This picture shows a strong serotonin immunoreactivity in the thoracic rat spinal cord white matter [...] Read more.
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Open AccessArticle Pretreatment with Group II Metabotropic Glutamate Receptor Agonist LY379268 Protects Neonatal Rat Brains from Oxidative Stress in an Experimental Model of Birth Asphyxia
Brain Sci. 2018, 8(3), 48; https://doi.org/10.3390/brainsci8030048
Received: 30 January 2018 / Revised: 14 March 2018 / Accepted: 15 March 2018 / Published: 17 March 2018
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Abstract
Hypoxia-ischemia (H-I) at the time of birth may cause neonatal death or lead to persistent brain damage. The search for an effective treatment of asphyxiated infants has not resulted in an effective therapy, and hypothermia remains the only available therapeutic strategy. Among possible
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Hypoxia-ischemia (H-I) at the time of birth may cause neonatal death or lead to persistent brain damage. The search for an effective treatment of asphyxiated infants has not resulted in an effective therapy, and hypothermia remains the only available therapeutic strategy. Among possible experimental therapies, the induction of ischemic tolerance is promising. Recent investigations have shown that activation of group II metabotropic glutamate receptors (mGluR2/3) can provide neuroprotection against H-I, but the mechanism of this effect is not clear. The aim of this study was to investigate whether an mGluR2/3 agonist applied before H-I reduces brain damage in an experimental model of birth asphyxia and whether a decrease in oxidative stress plays a role in neuroprotection. Neonatal H-I on seven-day-old rats was used as an experimental model of birth asphyxia. Rats were injected intraperitoneally with the mGluR2/3 agonist LY379268 24 or 1 h before H-I (5 mg/kg). LY379268 reduced the infarct area in the ischemic hemisphere. Application of the agonist at both times also reduced the elevated levels of reactive oxygen species (ROS) in the ipsilateral hemisphere observed after H-I and prevented the increase in antioxidant enzyme activity in the injured hemisphere. The decrease in glutathione (GSH) level was also restored after agonist application. The results suggest that the neuroprotective mechanisms triggered by the activation of mGluR2/3 before H-I act through the decrease of glutamate release and its extracellular concentration resulting in the inhibition of ROS production and reduction of oxidative stress. This, rather than induction of ischemic tolerance, is probably the main mechanism involved in the observed neuroprotection. Full article
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Open AccessReview Hallucinogen Persisting Perception Disorder: Etiology, Clinical Features, and Therapeutic Perspectives
Brain Sci. 2018, 8(3), 47; https://doi.org/10.3390/brainsci8030047
Received: 4 February 2018 / Revised: 12 March 2018 / Accepted: 13 March 2018 / Published: 16 March 2018
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Abstract
Hallucinogen Persisting Perception Disorder (HPPD) is a rare, and therefore, poorly understood condition linked to hallucinogenic drugs consumption. The prevalence of this disorder is low; the condition is more often diagnosed in individuals with a history of previous psychological issues or substance misuse,
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Hallucinogen Persisting Perception Disorder (HPPD) is a rare, and therefore, poorly understood condition linked to hallucinogenic drugs consumption. The prevalence of this disorder is low; the condition is more often diagnosed in individuals with a history of previous psychological issues or substance misuse, but it can arise in anyone, even after a single exposure to triggering drugs. The aims of the present study are to review all the original studies about HPPD in order to evaluate the following: (1) the possible suggested etiologies; (2) the possible hallucinogens involved in HPPD induction; (3) the clinical features of both HPPD I and II; (4) the possible psychiatric comorbidities; and (5) the available and potential therapeutic strategies. We searched PubMed to identify original studies about psychedelics and Hallucinogen Persisting Perception Disorder (HPPD). Our research yielded a total of 45 papers, which have been analyzed and tabled to provide readers with the most updated and comprehensive literature review about the clinical features and treatment options for HPPD. Full article
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Open AccessCommunication The Dynamic Environment of Crypto Markets: The Lifespan of New Psychoactive Substances (NPS) and Vendors Selling NPS
Brain Sci. 2018, 8(3), 46; https://doi.org/10.3390/brainsci8030046
Received: 27 January 2018 / Revised: 12 March 2018 / Accepted: 13 March 2018 / Published: 16 March 2018
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Abstract
The Internet has played a major role in the distribution of New Psychoactive Substances (NPS), and crypto markets are increasingly used for the anonymous sale of drugs, including NPS. This study explores the availability of individual NPS and vendors on the crypto markets
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The Internet has played a major role in the distribution of New Psychoactive Substances (NPS), and crypto markets are increasingly used for the anonymous sale of drugs, including NPS. This study explores the availability of individual NPS and vendors on the crypto markets and considers whether crypto markets are a reliable platform for the sale of NPS. Data was collected from 22 crypto markets that were accessed through the hidden web using the Onion Router (Tor). Data collection took place bimonthly from October 2015 to October 2016 as part of the CASSANDRA (Computer Assisted Solutions for Studying the Availability aNd DistRibution of novel psychoActive substances) project. In seven snapshots over 12 months, 808 unique vendors were found selling 256 unique NPS. The total number of individual NPS and vendors increased across the data collection period (increase of 93.6% and 71.6%, respectively). Only 24% (n = 61) of the total number of NPS and 4% (n = 31) of vendors appeared in every snapshot over the 12 months, whereas 21% (n = 54) of NPS and 45% (n = 365) of vendors only appeared once throughout the data collection. The individual NPS and vendors did not remain the same over the 12 months. However, the availability of NPS and vendors selling NPS grew. NPS consistently available on crypto markets could indicate popular substances. Full article
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Open AccessArticle l-Carnitine Modulates Epileptic Seizures in Pentylenetetrazole-Kindled Rats via Suppression of Apoptosis and Autophagy and Upregulation of Hsp70
Brain Sci. 2018, 8(3), 45; https://doi.org/10.3390/brainsci8030045
Received: 30 January 2018 / Revised: 3 March 2018 / Accepted: 9 March 2018 / Published: 14 March 2018
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Abstract
l-Carnitine is a unique nutritional supplement for athletes that has been recently studied as a potential treatment for certain neuropsychiatric disorders. However, its efficacy in seizure control has not been investigated. Sprague Dawley rats were randomly assigned to receive either saline (Sal)
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l-Carnitine is a unique nutritional supplement for athletes that has been recently studied as a potential treatment for certain neuropsychiatric disorders. However, its efficacy in seizure control has not been investigated. Sprague Dawley rats were randomly assigned to receive either saline (Sal) (negative control) or pentylenetetrazole (PTZ) 40 mg/kg i.p. × 3 times/week × 3 weeks. The PTZ group was further subdivided into two groups, the first received oral l-carnitine (l-Car) (100 mg/kg/day × 4 weeks) (PTZ + l-Car), while the second group received saline (PTZ + Sal). Daily identification and quantification of seizure scores, time to the first seizure and the duration of seizures were performed in each animal. Molecular oxidative markers were examined in the animal brains. l-Car treatment was associated with marked reduction in seizure score (p = 0.0002) that was indicated as early as Day 2 of treatment and continued throughout treatment duration. Furthermore, l-Car significantly prolonged the time to the first seizure (p < 0.0001) and shortened seizure duration (p = 0.028). In addition, l-Car administration for four weeks attenuated PTZ-induced increase in the level of oxidative stress marker malondialdehyde (MDA) (p < 0.0001) and reduced the activity of catalase enzyme (p = 0.0006) and increased antioxidant GSH activity (p < 0.0001). Moreover, l-Car significantly reduced PTZ-induced elevation in protein expression of caspase-3 (p < 0.0001) and β-catenin (p < 0.0001). Overall, our results suggest a potential therapeutic role of l-Car in seizure control and call for testing these preclinical results in a proof of concept pilot clinical study. Full article
(This article belongs to the Special Issue Diagnosis and Surgical Treatment of Epilepsy)
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Open AccessEditorial Pathophysiology and Imaging Diagnosis of Demyelinating Disorders
Brain Sci. 2018, 8(3), 44; https://doi.org/10.3390/brainsci8030044
Received: 9 March 2018 / Revised: 12 March 2018 / Accepted: 12 March 2018 / Published: 14 March 2018
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Abstract
The spectrum of “demyelinating disorders” is broad and it includes various disorders with central nervous system (CNS) demyelination[...] Full article
Open AccessReview Mood Fluctuation and Psychobiological Instability: The Same Core Functions Are Disrupted by Novel Psychoactive Substances and Established Recreational Drugs
Brain Sci. 2018, 8(3), 43; https://doi.org/10.3390/brainsci8030043
Received: 30 January 2018 / Revised: 28 February 2018 / Accepted: 6 March 2018 / Published: 13 March 2018
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Abstract
Many novel psychoactive substances (NPS) have entered the recreational drug scene in recent years, yet the problems they cause are similar to those found with established drugs. This article will debate the psychobiological effects of these newer and more traditional substances. It will
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Many novel psychoactive substances (NPS) have entered the recreational drug scene in recent years, yet the problems they cause are similar to those found with established drugs. This article will debate the psychobiological effects of these newer and more traditional substances. It will show how they disrupt the same core psychobiological functions, so damaging well-being in similar ways. Every psychoactive drug causes mood states to fluctuate. Users feel better on-drug, then feel worse off-drug. The strength of these mood fluctuations is closely related to their addiction potential. Cyclical changes can occur with many other core psychobiological functions, such as information processing and psychomotor speed. Hence the list of drug-related impairments can include: homeostatic imbalance, HPA axis disruption, increased stress, altered sleep patterns, neurohormonal changes, modified brain rhythms, neurocognitive impairments, and greater psychiatric vulnerability. Similar patterns of deficit are found with older drugs such as cocaine, nicotine and cannabis, and newer substances such as 3,4-methylenedioxymethamphetamine (MDMA), mephedrone and spice. All psychoactive drugs damage human well-being through similar basic neuropsychobiological mechanisms. Full article
Open AccessCase Report Epilepsy Surgery for Skull-Base Temporal Lobe Encephaloceles: Should We Spare the Hippocampus from Resection?
Brain Sci. 2018, 8(3), 42; https://doi.org/10.3390/brainsci8030042
Received: 31 January 2018 / Revised: 7 March 2018 / Accepted: 8 March 2018 / Published: 12 March 2018
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Abstract
The neurosurgical treatment of skull base temporal encephalocele for patients with epilepsy is variable. We describe two adult cases of temporal lobe epilepsy (TLE) with spheno-temporal encephalocele, currently seizure-free for more than two years after anterior temporal lobectomy (ATL) and lesionectomy sparing the
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The neurosurgical treatment of skull base temporal encephalocele for patients with epilepsy is variable. We describe two adult cases of temporal lobe epilepsy (TLE) with spheno-temporal encephalocele, currently seizure-free for more than two years after anterior temporal lobectomy (ATL) and lesionectomy sparing the hippocampus without long-term intracranial electroencephalogram (EEG) monitoring. Encephaloceles were detected by magnetic resonance imaging (MRI) and confirmed by maxillofacial head computed tomography (CT) scans. Seizures were captured by scalp video-EEG recording. One case underwent intraoperative electrocorticography (ECoG) with pathology demonstrating neuronal heterotopia. We propose that in some patients with skull base temporal encephaloceles, minimal surgical resection of herniated and adjacent temporal cortex (lesionectomy) is sufficient to render seizure freedom. In future cases, where an associated malformation of cortical development is suspected, newer techniques such as minimally invasive EEG monitoring with stereotactic-depth EEG electrodes should be considered to tailor the surrounding margins of the resected epileptogenic zone. Full article
(This article belongs to the Special Issue Diagnosis and Surgical Treatment of Epilepsy)
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Open AccessArticle Brain Response to Non-Painful Mechanical Stimulus to Lumbar Spine
Brain Sci. 2018, 8(3), 41; https://doi.org/10.3390/brainsci8030041
Received: 21 December 2017 / Revised: 15 February 2018 / Accepted: 22 February 2018 / Published: 1 March 2018
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Abstract
Pressure application to the lumbar spine is an important assessment and treatment method of low back pain. However, few studies have characterized brain activation patterns in response to mechanical pressure. The objective of this study was to map brain activation associated with various
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Pressure application to the lumbar spine is an important assessment and treatment method of low back pain. However, few studies have characterized brain activation patterns in response to mechanical pressure. The objective of this study was to map brain activation associated with various levels of mechanical pressure to the lumbar spine in healthy subjects. Fifteen healthy subjects underwent functional magnetic resonance imaging (fMRI) scanning while mechanical pressure was applied to their lumbar spine with a custom-made magnetic resonance imaging (MRI)-compatible pressure device. Each subject received three levels of pressure (low/medium/high) based on subjective ratings determined prior to the scan using a block design (pressure/rest). Pressure rating was assessed with an 11-point scale (0 = no touch; 10 = max pain-free pressure). Brain activation differences between pressure levels and rest were analyzed. Subjective pressure ratings were significantly different across pressure levels (p < 0.05). The overall brain activation pattern was not different across pressure levels (all p > 0.05). However, the overall effect of pressure versus rest showed significant decreases in brain activation in response to the mechanical stimulus in regions associated with somatosensory processing including the precentral gyri, left hippocampus, left precuneus, left medial frontal gyrus, and left posterior cingulate. There was increase in brain activation in the right inferior parietal lobule and left cerebellum. This study offers insight into the neural mechanisms that may relate to manual mobilization intervention used for managing low back pain. Full article
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Open AccessReview The Effects of Cannabinoids on Executive Functions: Evidence from Cannabis and Synthetic Cannabinoids—A Systematic Review
Brain Sci. 2018, 8(3), 40; https://doi.org/10.3390/brainsci8030040
Received: 22 January 2018 / Revised: 8 February 2018 / Accepted: 24 February 2018 / Published: 27 February 2018
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Abstract
Background—Cannabis is the most popular illicit drug in the Western world. Repeated cannabis use has been associated with short and long-term range of adverse effects. Recently, new types of designer-drugs containing synthetic cannabinoids have been widespread. These synthetic cannabinoid drugs are associated with
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Background—Cannabis is the most popular illicit drug in the Western world. Repeated cannabis use has been associated with short and long-term range of adverse effects. Recently, new types of designer-drugs containing synthetic cannabinoids have been widespread. These synthetic cannabinoid drugs are associated with undesired adverse effects similar to those seen with cannabis use, yet, in more severe and long-lasting forms. Method—A literature search was conducted using electronic bibliographic databases up to 31 December 2017. Specific search strategies were employed using multiple keywords (e.g., “synthetic cannabinoids AND cognition,” “cannabis AND cognition” and “cannabinoids AND cognition”). Results—The search has yielded 160 eligible studies including 37 preclinical studies (5 attention, 25 short-term memory, 7 cognitive flexibility) and 44 human studies (16 attention, 15 working memory, 13 cognitive flexibility). Both pre-clinical and clinical studies demonstrated an association between synthetic cannabinoids and executive-function impairment either after acute or repeated consumptions. These deficits differ in severity depending on several factors including the type of drug, dose of use, quantity, age of onset and duration of use. Conclusions—Understanding the nature of the impaired executive function following consumption of synthetic cannabinoids is crucial in view of the increasing use of these drugs. Full article
Open AccessArticle Abstraction and Idealization in Biomedicine: The Nonautonomous Theory of Acute Cell Injury
Brain Sci. 2018, 8(3), 39; https://doi.org/10.3390/brainsci8030039
Received: 30 January 2018 / Revised: 21 February 2018 / Accepted: 23 February 2018 / Published: 27 February 2018
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Abstract
Neuroprotection seeks to halt cell death after brain ischemia and has been shown to be possible in laboratory studies. However, neuroprotection has not been successfully translated into clinical practice, despite voluminous research and controlled clinical trials. We suggested these failures may be due,
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Neuroprotection seeks to halt cell death after brain ischemia and has been shown to be possible in laboratory studies. However, neuroprotection has not been successfully translated into clinical practice, despite voluminous research and controlled clinical trials. We suggested these failures may be due, at least in part, to the lack of a general theory of cell injury to guide research into specific injuries. The nonlinear dynamical theory of acute cell injury was introduced to ameliorate this situation. Here we present a revised nonautonomous nonlinear theory of acute cell injury and show how to interpret its solutions in terms of acute biomedical injuries. The theory solutions demonstrate the complexity of possible outcomes following an idealized acute injury and indicate that a “one size fits all” therapy is unlikely to be successful. This conclusion is offset by the fact that the theory can (1) determine if a cell has the possibility to survive given a specific acute injury, and (2) calculate the degree of therapy needed to cause survival. To appreciate these conclusions, it is necessary to idealize and abstract complex physical systems to identify the fundamental mechanism governing the injury dynamics. The path of abstraction and idealization in biomedical research opens the possibility for medical treatments that may achieve engineering levels of precision. Full article
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Open AccessArticle Effects of Dietary Vitamin E Supplementation in Bladder Function and Spasticity during Spinal Cord Injury
Brain Sci. 2018, 8(3), 38; https://doi.org/10.3390/brainsci8030038
Received: 26 January 2018 / Revised: 23 February 2018 / Accepted: 23 February 2018 / Published: 26 February 2018
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Abstract
Traumatic spinal cord injury (SCI) results in debilitating autonomic dysfunctions, paralysis and significant sensorimotor impairments. A key component of SCI is the generation of free radicals that contributes to the high levels of oxidative stress observed. This study investigates whether dietary supplementation with
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Traumatic spinal cord injury (SCI) results in debilitating autonomic dysfunctions, paralysis and significant sensorimotor impairments. A key component of SCI is the generation of free radicals that contributes to the high levels of oxidative stress observed. This study investigates whether dietary supplementation with the antioxidant vitamin E (alpha-tocopherol) improves functional recovery after SCI. Female adult Sprague-Dawley rats were fed either with a normal diet or a dietary regiment supplemented with vitamin E (51 IU/g) for eight weeks. The rats were subsequently exposed either to a contusive SCI or sham operation, and evaluated using standard functional behavior analysis. We report that the rats that consumed the vitamin E-enriched diet showed an accelerated bladder recovery and significant improvements in locomotor function relative to controls, as determined by residual volumes and Basso, Beatie, and Bresnaham BBB scores, respectively. Interestingly, the prophylactic dietary intervention did not preserve neurons in the ventral horn of injured rats, but it significantly increased the numbers of oligodendrocytes. Vitamin E supplementation attenuated the depression of the H-reflex (a typical functional consequence of SCI) while increasing the levels of supraspinal serotonin immunoreactivity. Our findings support the potential complementary use of vitamin E to ameliorate sensory and autonomic dysfunctions associated with spinal cord injury, and identified promising new cellular and functional targets of its neuroprotective effects. Full article
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