B, High-signal-intensity changes involve the frontal and parietal periventricular white matter (arrowheads). Separate sets of rats were exposed to the toluene via inhalation, at 1,500 ppm and at 10,000 ppm respectively, and via an ingestion (400 mg/kg). The neurotoxic effects of long-term use (in particular repeated withdrawals) of toluene may cause postural tremors by upregulating GABA receptors within the cerebellar cortex. Patients with findings of abnormal white matter changes had a mean duration of abuse of 6.8 years (range, 3–11 years). All patients with diffuse white matter changes had findings of cerebral-cerebellar atrophy and thinning of the corpus callosum. Zhonghua Yi Xue Za Zhi. The low cost and easy availability of organic solvents have led to increases in the number of young abusers in many countries. A, High signal intensity is seen in the centrum semiovale (arrows) on both sides. Demyelination and gliosis are the histopathologic changes underlying these white matter lesions on cranial MR images (5, 6). Liquid thinner, an organic solvent used in painting, was the substance abused by all of our patients. Toluene exposure during brain growth spurt and adolescence produces differential effects on N-methyl-D-aspartate receptor-mediated currents in rat hippocampus. With a similar mechanism, demyelination and axonal loss induced by the chronic inhalation of toluene may reach a level sufficient to cause iron deposition and thalamic hypointensity on T2-weighted images. This disrupts your normal brain activity. The alterations in GABA(A) receptors might be associated with the neurobehavioral disturbance in offspring of toluene-abusing women. Toluene and xylene are strong compounds that are used in many household and industrial products. RATIONALE: The abused inhalant toluene has potent behavioral effects, but only recently has progress been made in understanding the neurochemical actions that mediate the action of toluene in the brain. Note that gray matter-white matter differentiation is lost in the anterior part of the left temporal lobe. effects such as reductions in thinking, memory, and muscular abilities, as well as some losses in hearing and color vision. Mean duration of abuse was 4.6 years (range, 1–11 years). The dopamine system has been shown to play a role in the rewarding effects of nearly all drugs of abuse. The relative abundance of the mRNAs encoding various subunits of GABA(A) receptor (alpha1, alpha2, alpha4, alpha5, alpha6, beta2, beta3, gamma2S, gamma2L) was examined in four brain regions (hippocampus, striatum, cortex, and cerebellum) by semiquantitative reverse transcription-PCR. For example, toluene exposure increased NQO 1 activity at 4 and 12 mos in FC and Cb but only at 24 mos in Hip. A suggests that the hyperintense findings may be caused by terminal myelination, which is a normal MR imaging finding in children. With all sequences, a 192–256 × 200–256 matrix and a 180–225 × 200–225-mm field of view were used. 2009 Sep;34(10):2296-304. doi: 10.1038/npp.2009.57. Similarly, age and toluene effects on glutathione enzymes were varied and brain-region specific. Of 41 patients, 34 (83%) reported insomnia and forgetfulness; 30 (73%), anosmia; 22 (54%), tremors of the extremities; and 15 (37%), tinnitus. Brain Res Bull. T1-weighted and T2-weighted images showed atrophic dilatation of ventricles and cerebral and cerebellar sulci in 11 patients (27%). Although the partition of toluene into brain lipids may theoretically contribute to the development of thalamic hypointensity, it does not seem to be the major factor. Toxicol Lett. The development of white matter changes and thalamic hypointensity were signficantly associated with duration of abuse longer than 4 years (P < .05 and P < .01, respectively). Toluene and xylene poisoning can occur when someone swallows these substances, breathes in their fumes, or when these substances touch the skin. 1. Neuropsychopharmacology. Toluene vapor has a sharp or sweet odor, which is a sign of exposure. However, white matter changes were not significantly associated with age at onset of abuse (P > .05). The associations of chronic toluene inhalation with cognitive impairment, psychiatric disorders, spasticity, and Parkinson disease have been reported (18–24). White matter changes were restricted in 53% and diffuse in 47%. In vitro intracellular electrophysiological recordings employing brain slices from rats treated with toluene demonstrated a significant decrease in GABA(A) receptor-mediated inhibitory postsynaptic currents in CA1 neurons but an increased … Thank you for your interest in spreading the word on American Journal of Neuroradiology. Demyelination and gliosis in the cerebral and cerebellar white matter are the histologic changes reported in chronic toluene abusers (5, 6). 2007 Jan 23;87(4):275-8. The most toxic chemicals detected – formaldehyde, benzene, chloroform and toluene – are not listed on the label. Because of its high lipid solubility, toluene accumulates in lipid-rich tissues such as brain. C, Sagittal T1-weighted (600/15/1) midline image shows thinning of the corpus callosum, which is more prominent in the body and genu. Disorders of the muscles, cardiovascular effects, renal tubular damage, and su… Test was performed on PN 58. Markers of oxidative damage reflected changes in oxidative stress. The main constituent in most modern solvents is toluene (C7H8), also known as methylbenzene, a lipid-soluble aromatic hydrocarbon. 2014 May;104:27-35. doi: 10.1016/j.brainresbull.2014.04.001. Note that the lateral ventricles and cerebral sulci are enlarged. Diffuse changes were widespread, extending to subcortical white matter, with focal or diffuse loss of gray matter-white matter differentiation. However, myelin is only present in the white matter, but intelligence is related … In vitro intracellular electrophysiological recordings employing brain slices from rats treated with toluene demonstrated a significant decrease in GABA(A) receptor-mediated inhibitory postsynaptic currents in CA1 neurons but an increased response to GABA perfusion. Once it enters the bloodstream, either through the respiratory organs, alimentary tract and transdermal absorption, toluene can reach the brain by crossing the blood-brain barrier. Given these three exposure conditions, the values of The results of our study support this suggestion. HHS This site needs JavaScript to work properly. Symmetric hypointensity in the thalami and basal ganglia on T2-weighted cranial MR images is also reported in chronic solvent abuse (8, 10, 11).  |  A new study shows inhaling toluene, a compound commonly found in products like paint thinner and glue, triggers the release of dopamine in the brain of laboratory rats. General Effects of Inhalants on the Brain. M. Kanter, “Protective effects of Nigella sativa on the neuronal injury in frontal cortex and brain stem after chronic toluene exposure,” Neurochemical Research, vol. A and B, Bilateral, symmetric hyperintensity is present in the parietal periventricular white matter (arrowheads). The regional distribution of toluene in the brain and its effects on the brain catecholamine levels in rats is reported. They suggested that the accumulation of iron might cause thalamic hypointensity. Examples of the health effects of specific organic solvents include: Alcohols, such as denatured ethanol depress the central nervous system, and cause irritation to the eyes and upper respiratory tract. 2241–2249, 2008. We examined the corpus callosum by using the method Weis et al (12) described. This article has not yet been cited by articles in journals that are participating in Crossref Cited-by Linking. Axial T2-weighted (2900/85/2 [TR/TE/NEX]) images in a 16-year-old patient who had inhaled toluene for 6 years. Early caffeine exposure: transient and long-term consequences on brain excitability. Intensive treatment is necessary to prevent death. Yamanouchi et al (8) also suggested that restricted white matter changes might be an early stage of diffuse white matter changes. ioral and neurotoxicological effects. Toluene inhalation causes activation and morphologic changes of astrocytes in the rat brain, especially in the cerebellum and hippocampus (26, 27). Demyelination and gliosis are histologically demonstrable in regions of abnormal T2 signal. Exposure to extremely high levels that may occur with inhalation abuse has demonstrated that toluene can cause permanent toxicity to the brain. The current theory "CNS toxicity may be due to the liposolubility of toluene in the neuronal membrane. Toxicol Sci. Br J Pharmacol. No studies are currently available on the effects of long-term exposure to white spitit but two such studies are available on jet fuel. Some workers have developed reversible disorders of the optic nerves after chronic exposure in the workplace. The mean duration of abuse of patients with diffuse white matter changes was 7.9 years (range, 6–11 years). NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. Epub 2007 Oct 20. Animal and human research shows that most inhalants are extremely toxic. In 1951, Clinger et al (13) reported the first cases of volatile substance abuse by inhalation. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. [Long-term effects of recurrent seizures in neonate period on gamma-aminobutyric acid A receptor alpha1 and beta2 subunits expression in adult brain: experiment with rats]. All patients with thalamic hypointensity had cerebral-cerebellar atrophy. Once it enters the bloodstream, either through the respiratory organs, alimentary tract and transdermal absorption, toluene can reach the brain by crossing the blood-brain barrier. Clipboard, Search History, and several other advanced features are temporarily unavailable. The effects vary by dosage, such that individuals who inhale for longer periods of time will achieve different or more powerful effects. Xiong et al (7) and Yamanouchi et al (8) described white matter changes in the centrum semiovale, posterior limb of the internal capsule, the ventral part of pons, the cerebellar peduncles, and the cerebellar white matter on cranial MR images in patients who chronically abuse toluene. The current theory "CNS toxicity may be due to the liposolubility of toluene in the neuronal membrane. However, myelin is only present in the white matter, but intelligence is related to the grey matter which does not contain myelin. Toluene is the major component of organic industrial solvents that is thought to cause the neurotoxicity seen in solvent abusers (3, 4). Toluene inhalation causes activation and morphologic changes of astrocytes in the rat brain, especially in the cerebellum and hippocampus (26, 27). Long-term inhalation of toluene-containing solvents causes irreversible central nervous system damage. The results of the experimental study conducted by Unger et al demonstrated the correlation of the degree of hypointensity on T2-weighted images with the concentration of toluene. Axial T2-weighted (3000/80/2 [TR/TE/NEX]) images in a 16-year-old patient who had inhaled thinner for 3 years. 2008 Feb;101(2):286-93. doi: 10.1093/toxsci/kfm264. such as may occur in glue-sniffing, toluene has been reported to cause damage to the cerebellum (a part of the brain that controls balance). Toluene is degraded into benzoic acid by oxidation and is conjugated with glycine to form hippuric acid in the liver. And your brain being the organ most vulnerable to even small scale disruptions, it shouldn't be surprising its effects show up there most. MR images in a 19-year-old patient who had abused toluene for 8 years. toluene also causes irritation of the upper respiratory tract and eyes, sore throat, dizziness, and headache. A total of 20 male rabbits were used as control and experimental groups. Depending on the time spent inhaling, one may begin to feel a slight stimulant effect and a loss of inhibitions. All patients were homeless people who were admitted for a solvent-abuse rehabilitation program. The regional distribution of toluene in the brain and its effects on the brain catecholamine levels in rats is reported. Examples of the health effects of specific organic solvents include: Alcohols, such as denatured ethanol depress the central nervous system, and cause irritation to the eyes and upper respiratory tract. B, Axial T2-weighted (2620/85/2) image at the level of lower medulla oblongata shows symmetric hyperintensity along the spinocerebellar tracts (arrowheads). Two neuroradiologists (K.A., S.S.) independently interpreted images. By affecting the transmission of nerve impulses and neurotransmitters (brain hormones), … Cranial MR Findings in Chronic Toluene Abuse by Inhalation, Addictive Illegal Drugs: Structural Neuroimaging, Smaller Gray Matter Volumes in Frontal and Parietal Cortices of Solvent Abusers Correlate with Cognitive Deficits, White Matter Alterations in the Brains of Patients with Active, Remitted, and Cured Cushing Syndrome: A DTI Study, Qualitative and Quantitative Analysis of MR Imaging Findings in Patients with Middle Cerebral Artery Stroke Implanted with Mesenchymal Stem Cells, Fast Contrast-Enhanced 4D MRA and 4D Flow MRI Using Constrained Reconstruction (HYPRFlow): Potential Applications for Brain Arteriovenous Malformations, Thanks to our 2020 Distinguished Reviewers, Copyright © American Society of Neuroradiology. Contrary to this hypothesis, T2-weighted images in 51% of our patients did not reveal thalamic hypointensity, although the daily thinner consumption in our patients reached the plateau in their 3rd year of abuse. The significant association between the development of thalamic hypointensity and the duration of abuse suggests that thalamic hypointensity develops as a result of a chronic abuse. After a period of abstinence of 4 to 7 days, all patients underwent cranial MR examination on a system equipped with a 1.0-T superconducting magnet (Magnetom; Siemens, Erlangen, Germany). The pattern of white matter changes is compatible with that of the restricted type. Its neurobiological effects are, at least in part, mediated by gamma-aminobutyric acid (GABA(A)) receptors. CONCLUSION: White matter changes seem to start in the deep periventricular white matter, and they spread into peripheral white matter, causing the loss of gray matter-white matter differentiation with continued toluene abuse. Chronic toluene exposures at less than 200 ppm have been associated with headache, fatigue, and nausea. The effects of toluene generally last several hours and include euphoria, grandiosity, reduced inhibitions, feelings of inebriation, floating sensation, drowsiness, sedation, reduced ability to concentrate, distorted perception of time and distance, weakness, lethargy, fatigue, memory loss, … The seizure sensitivity induced by bicuculline (a GABA(A) receptor antagonist), methyl beta-carboline-3-carboxylate (inverse agonists of the GABA(A)/benzodiazepine receptor) but not 3-mercaptopropionic acid (a glutamate decarboxylase inhibitor) was enhanced by toluene exposure. Note the enlarged cerebellar sulci. The clinical syndrome, toluene leukoencephalopathy, can be detected by a combination of characteristic symptoms and signs, detailed neurobehavioral evaluation, and brain magnetic resonance imaging. The most common restricted white matter changes revealed by T2-weighted imaging were patchy, high signal intensity in parietal areas, frontal periventricular areas, or both (Fig 4). We did not identify cortical hypointensity in any T2-weighted images. Toluene effects on several OS endpoints were age-and brain region-specific. Therefore, pathologic-radiologic correlation was not possible. One patient had had recent episodes of generalized convulsions. Organic solvent inhalation is a common form of substance abuse in children and young adults (1, 2). To extend knowledge in this area, we examined effects in rat brain of the volatile organic compound toluene. Some investigators have suggested that iron deposition and the partition of toluene into the lipids of cell membranes explain this finding (8, 11). COVID-19 is an emerging, rapidly evolving situation. Histologic findings at autopsy in one of their patients who died from a toluene overdose did not show thalamic iron deposition. The significant association of white matter changes on cranial MR images with the degree of cognitive impairment has been reported (25). Stupor, delirium, and drowsiness give way to seizures and coma. Periventricular white matter and the centrum semiovale were the most common locations for white matter changes in 19 (46%) of 41 patients (Fig 1). Human studies have reported developmental effects, such as CNS dysfunction, attention deficits, and minor craniofacial and limb anomalies, in the children of pregnant women exposed to high levels of toluene or mixed solvents by inhalation. 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