Acute neurotoxicity of acetaminophen in chicks

Acetaminophen is a non-steroidal drug used as an anti-inflammatory, analgesic and antipyretic in humans and animals. In chicks, neurotoxicity associated with acetaminophen has not been fully elucidated. The aim of this study was to identify the neurobehavioral, biochemical and histopathological effects of acetaminophen in 7 day-old broiler chicks. The acute LD50 of acetaminophen was estimated by the up- and- down method, and then the influence of acetaminophen on the open field activity and tonic immobility test was recorded. The behavioral signs and toxicity scores were recorded. The liver enzymes, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were estimated. Histopathology of the brain and liver were performed. The acetaminophen LD50 value in chicks was 1077 mg/kg, intramuscularly. Acetaminophen reduced the general locomotive activity of the chicks, measured in the open- field arena, as a result of a significant rise in latency in moving from the central square, and a reduction in the numbers of lines crossed as well as reduction in the vocalization score compared to the control. Intramuscular injections of acetaminophen at doses of 500 and 1000 mg/kg induced signs of toxicosis, such as head dropping, closed eyelids, immobility, loss of vocalization, and recumbency, followed by death. Histopathological examination of the brain showed the presence of congestion of blood vessels, vasogenic edema and necrosis of Purkinje cells. Degenerative changes and liver enzyme function showed liver dysfunction. Our results show behavioral, biochemical and histopathological data demonstrating that acetaminophen at high doses produced acute neurotoxicity in chicks.

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Fever produced by microinjection of typhoid vaccine into hypothalamus of cats

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1965.208.4.703 ◽

1965 ◽

Vol 208 (4) ◽

pp. 703-707 ◽

Cited By ~ 59

Author(s):

J. Villablanca ◽

R. D. Myers

Keyword(s):

Significant Rise ◽

Anterior Hypothalamus ◽

Cerebral Ventricle ◽

Intravenous Route ◽

Rapid Rise ◽

Typhoid Vaccine ◽

Brain Areas ◽

High Doses ◽

The Brain ◽

Lateral Cerebral Ventricle

In unanesthetized cats, 1 or 2.5 µliters typhoid vaccine were injected into several areas of the hypothalamus, the lateral cerebral ventricle, and other areas of the brain. The concentrations of the pyrogen used ranged from 1/8 to 1/16,000 of the dose required to produce fever by the intravenous route. Fever was obtained in all experiments in which the vaccine was applied to the anterior hypothalamus or to the lateral cerebral ventricle. No significant rise in temperature occurred following injections into other brain areas unless extremely high doses were employed. The short latency and the rapid rise in temperature following the injection of typhoid vaccine into the anterior hypothalamus suggest that pyrogens act on the cells of this diencephalic structure when fever is produced.

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DNA Methylation Profiles of Tph1A and BDNF in Gut and Brain of L. Rhamnosus-Treated Zebrafish

Biomolecules ◽

10.3390/biom11020142 ◽

2021 ◽

Vol 11 (2) ◽

pp. 142

Author(s):

Mariella Cuomo ◽

Luca Borrelli ◽

Rosa Della Monica ◽

Lorena Coretti ◽

Giulia De Riso ◽

...

Keyword(s):

Dna Methylation ◽

Molecular Mechanisms ◽

The Past ◽

Targeted Analysis ◽

Lack Of Information ◽

High Resolution Power ◽

Resolution Level ◽

Health And Disease ◽

High Doses ◽

The Brain

The bidirectional microbiota–gut–brain axis has raised increasing interest over the past years in the context of health and disease, but there is a lack of information on molecular mechanisms underlying this connection. We hypothesized that change in microbiota composition may affect brain epigenetics leading to long-lasting effects on specific brain gene regulation. To test this hypothesis, we used Zebrafish (Danio Rerio) as a model system. As previously shown, treatment with high doses of probiotics can modulate behavior in Zebrafish, causing significant changes in the expression of some brain-relevant genes, such as BDNF and Tph1A. Using an ultra-deep targeted analysis, we investigated the methylation state of the BDNF and Tph1A promoter region in the brain and gut of probiotic-treated and untreated Zebrafishes. Thanks to the high resolution power of our analysis, we evaluated cell-to-cell methylation differences. At this resolution level, we found slight DNA methylation changes in probiotic-treated samples, likely related to a subgroup of brain and gut cells, and that specific DNA methylation signatures significantly correlated with specific behavioral scores.

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Synergistic Effect of Several Neurotransmitters in PFC-NAc-VTA Neural Circuit for the Anti-Depression Effect of Shuganheweitang in a Chronic Unpredictable Mild Stress Model

Natural Product Communications ◽

10.1177/1934578x211002415 ◽

2021 ◽

Vol 16 (3) ◽

pp. 1934578X2110024

Author(s):

Xin Chen ◽

Yuanchun Ma ◽

Xiongjun Mou ◽

Hao Liu ◽

Hao Ming ◽

...

Keyword(s):

Animal Behavior ◽

Neural Circuit ◽

Concentration Level ◽

Brain Regions ◽

Mild Stress ◽

Depression Effect ◽

Monoamine Neurotransmitters ◽

Reward Circuitry ◽

High Doses ◽

The Brain

Depression, a major worldwide mental disorder, leads to massive disability and can result in death. The PFC-NAc-VTA neuro circuit is related to emotional, neurovegetative, and cognitive functions, which emerge as a circuit-level framework for understanding reward deficits in depression. Neurotransmitters, which are widely distributed in different brain regions, are important detected targets for the evaluation of depression. Shuganheweitang (SGHWT) is a popular prescription in clinical therapy for depression. In order to investigate its possible pharmacodynamics and anti-depressive mechanism, the complex plant material was separated into different fractions. These in low and high doses, along with low and high doses of SGHWT were tested in animal behavior tests. The low and high doses of SGHWT were more effective than the various fractions, which indicate the importance of synergistic function in traditional Chinese medicine. Furthermore, amino acid (GABA, Glu) and monoamine neurotransmitters (DA, 5-HT, NA, 5-HIAA) in the PFC-NAc-VTA neuro circuit were investigated by UPLC-MS/MS. The level trend of DA and 5-HT were consistent in the PFC-NAc-VTA neuro circuit, whereas 5-HIAA was decreased in the PFC, Glu was decreased in the PFC and VTA, and NA and GABA were decreased in the NAc. The results indicate that the pathogenesis of depression is associated with dysfunction of the PFC-NAc-VTA neural circuit, mainly through the neural projection effects of neurotransmitters associated with various brain regions in the neural circuit. PCA and OPLS-DA score plots demonstrated the similarities of individuals within each group and the differences among the groups. In this study, SGHWT could regulate the concentration level of different neurotransmitters in the PFC-NAc-VTA neuro circuit to improve the depression, which benefitted from the recognition of the brain reward circuitry in mood disorders.

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Advances in Nano-Enabled Platforms for the Treatment of Depression

Polymers ◽

10.3390/polym13091431 ◽

2021 ◽

Vol 13 (9) ◽

pp. 1431

Author(s):

Fadzai P. Mutingwende ◽

Pierre P. D. Kondiah ◽

Philemon Ubanako ◽

Thashree Marimuthu ◽

Yahya E. Choonara

Keyword(s):

Drug Delivery ◽

Drug Toxicity ◽

Common Mental Disorder ◽

Antidepressant Drug ◽

Chemical Properties ◽

Controlled Drug Release ◽

Routes Of Administration ◽

Antidepressant Efficacy ◽

High Doses ◽

The Brain

Nanotechnology has aided in the advancement of drug delivery for the treatment of several neurological disorders including depression. Depression is a relatively common mental disorder which is characterized by a severe imbalance of neurotransmitters. Several current therapeutic regimens against depression display drawbacks which include low bioavailability, delayed therapeutic outcome, undesirable side effects and drug toxicity due to high doses. The blood–brain barrier limits the entry of the drugs into the brain matrix, resulting in low bioavailability and tissue damage due to drug accumulation. Due to their size and physico-chemical properties, nanotechnological drug delivery systems present a promising strategy to enhance the delivery of nanomedicines into the brain matrix, thereby improving bioavailability and limiting toxicity. Furthermore, ligand-complexed nanocarriers can improve drug specificity and antidepressant efficacy and reduce drug toxicity. Biopolymers and nanocarriers can also be employed to enhance controlled drug release and reduce the hepatic first-pass effect, hence reducing the dosing frequency. This manuscript reviews recent advances in different biopolymers, such as polysaccharides and other nanocarriers, for targeted antidepressant drug delivery to the brain. It probes nano-based strategies that can be employed to enhance the therapeutic efficacy of antidepressants through the oral, intranasal, and parenteral routes of administration.

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Experimental delayed radiation necrosis of the brain

Journal of Neurosurgery ◽

10.3171/jns.1979.51.5.0587 ◽

1979 ◽

Vol 51 (5) ◽

pp. 587-596 ◽

Cited By ~ 18

Author(s):

Albert N. Martins ◽

Ralph E. Severance ◽

James M. Henry ◽

Thomas F. Doyle

Keyword(s):

Rhesus Monkeys ◽

Radiation Necrosis ◽

Clinical Signs ◽

Control Group ◽

Content Type ◽

Brain Irradiation ◽

Primate Brain ◽

High Doses ◽

The Brain ◽

Male Rhesus

✓ The authors have designed an experiment to detect a hitherto unrecognized interaction between high doses of the glucocorticoid, dexamethasone, and brain irradiation. Eighteen juvenile male rhesus monkeys received 1800 rads to the whole brain in 8.5 minutes. For 1½ days before and 10½ days after the irradiation, nine animals received approximately 2.9 mg/kg/day of dexamethasone intramuscularly in addition to irradiation, while the remaining nine animals served as the control group and received saline. All animals eventually developed a progressive neurological syndrome, and died of delayed radiation necrosis of the brain. The two groups were compared with regard to latency to onset of clinical signs, survival time, and number, distribution, and location of lesions of radionecrosis. Large doses of dexamethasone did not alter the susceptibility of the primate brain to delayed radiation necrosis. Detailed morphological study of the radionecrotic lesions supports the hypothesis that most, if not all, of the lesions develop as the consequence of injury to blood vessels.

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Linear Accelerator as a Neurosurgical Tool for Stereotactic Radiosurgery

Neurosurgery ◽

10.1227/00006123-198803000-00002 ◽

1988 ◽

Vol 22 (3) ◽

pp. 454-464 ◽

Cited By ~ 212

Author(s):

Ken R. Winston ◽

Wendell Lutz

Keyword(s):

Computed Tomography ◽

Cerebral Angiography ◽

Linear Accelerator ◽

Photon Radiation ◽

Entire System ◽

High Doses ◽

Design And Testing ◽

Stereotactic Apparatus ◽

The Brain ◽

New System

Abstract A new system has been developed for stereotactically delivering prescribed high doses of radiation to precisely located volumes of approximately 0.6 to 10.0 ml within the brain. A Brown-Roberts-Wells stereotactic apparatus and a 6-MeV linear accelerator equipped with a special collimator (12.5 to 30 mm in diameter) have been adapted. The 20-mm collimator allows treatment of a nearly spherical volume of 2.1 ml. Outside the treatment field, the dosage declines to 80% of the dose prescribed for the periphery of the lesion over a distance of 1.8 mm and to 50% over the next 3.4 mm. Localization can be accomplished via computed tomography or cerebral angiography. Treatment is accomplished with an arcing beam of photon radiation with the turntable (couch) in each of four positions. The entire system has been extensively tested for accuracy in alignment and distribution of radiation. Errors have been measured for the alignment of the apparatus and for the process of localization. Safety of operation was emphasized throughout the design and testing phase. (Neurosurgery 22:454-464, 1988)

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Evaluation of the BDNF, NGF, NT3 and NT4 Genes Expressions in the Brains of Neonatal Mice with Hypothyroidism

Journal of Molecular Biology Research ◽

10.5539/jmbr.v7n1p171 ◽

2017 ◽

Vol 7 (1) ◽

pp. 171

Author(s):

Hamid Reza Adeli Bhroz ◽

Kazem Parivar ◽

Iraj Amiri ◽

Nasim Hayati Roodbari

Keyword(s):

Dose Group ◽

Low Dose ◽

Pure Water ◽

Intervention Group ◽

Control Group ◽

High Dose ◽

Endocrine Glands ◽

Blood Samples ◽

High Doses ◽

The Brain

Background and Aim: Thyroid is one of the endocrine glands, (T3 and T4) play a significant role in the development of prenatal brain and the following stages. The study aimed to evaluate the effect of hypothyroidism on the amount of expression of NT4, NT3, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in brain of one-day rat neonates with hypothyroidism.Materials and Methods: In total, 25 mature mice of Albino NMRI race were selected after mating, divided into three group, control, as well as low-dose and high-dose intervention groups. Samples of the control group received pure water during pregnancy, whereas subjects of the intervention group with low and high doses of the medication were administered with 20 mg and 100 mg methimazole powder (dissolved in 100 cc water), respectively. After child delivery, blood samples were obtained from mother mice to determine the level of T3 and T4 in blood serum. Following that, the brain of one-day mice were removed by surgery and assessed to determine the amount of expression of NT4, NT3, NGF and BDNF using the complete kit of RT-PCR.Results: Levels of T4 and T3 in the control group were 28 ug/dl and 1.59 ug/dl, respectively. In the low-dose intervention group, the amounts of the mentioned hormones were 8 ug/dl and 0.85 ug/dl, significantly, indicating a significant reduction in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group. Moreover, T4 and T3 were 6 ug/dl and 0.79 ug/dl in the high-dose group, respectively, conveying a significant decrease in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group (P<0.05).

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Modafinil Effects on Behavior and Oxidative Damage Parameters in Brain of Wistar Rats

Behavioural Neurology ◽

10.1155/2014/917246 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Felipe Ornell ◽

Samira S. Valvassori ◽

Amanda V. Steckert ◽

Pedro F. Deroza ◽

Wilson R. Resende ◽

...

Keyword(s):

Oxidative Damage ◽

Open Field ◽

Wistar Rats ◽

Thiobarbituric Acid ◽

Protein Carbonyl ◽

Behavioral Changes ◽

Protein Damage ◽

Behavioral Parameters ◽

Carbonyl Formation ◽

The Brain

The effects of modafinil (MD) on behavioral and oxidative damage to protein and lipid in the brain of rats were evaluated. Wistar rats were given a single administration by gavage of water or MD (75, 150, or 300 mg/kg). Behavioral parameters were evaluated in open-field apparatus 1, 2, and 3 h after drug administration. Thiobarbituric acid reactive substances (TBARS) and protein carbonyl formation were measured in the brain. MD increased locomotor activity at the highest dose 1 and 3 h after administration. MD administration at the dose of 300 mg/kg increased visits to the center of open-field 1 h after administration; however, 3 h after administration, all administered doses of MD increased visits to the open-field center. MD 300 mg/kg increased lipid damage in the amygdala, hippocampus, and striatum. Besides, MD increased protein damage in the prefrontal cortex, amygdala, and hippocampus; however, this effect varies depending on the dose administered. In contrast, the administration of MD 75 and 300 mg/kg decreased the protein damage in the striatum. This study demonstrated that the MD administration induces behavioral changes, which was depending on the dose used. In addition, the effects of MD on oxidative damage parameters seemed to be in specific brain region and doses.

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Clinical, MRI, and Histopathological Features of Hypothalamic Neuronal Hamartoma in a Young Vizsla

Journal of the American Animal Hospital Association ◽

10.5326/jaaha-ms-7083 ◽

2021 ◽

Author(s):

Leonardo Bibbiani ◽

Sara Canal ◽

Daiana Marabese ◽

Maria T. Mandara ◽

Greta Foiani ◽

...

Keyword(s):

Congenital Malformations ◽

Histopathological Examination ◽

Middle Cranial Fossa ◽

Clinical Imaging ◽

First Report ◽

Histopathological Features ◽

Neurological Signs ◽

Cranial Fossa ◽

The Brain ◽

Clinical Mri

ABSTRACT Human hypothalamic neuronal hamartomas are rare, nonprogressive, congenital malformations of the hypothalamus that do not expand or metastasize to other locations. A 1 yr old female vizsla was presented for progressive intracranial multifocal neurological signs already present since adoption at 3 mo of age. MRI of the brain showed an ill-defined, intra-axial, space-occupying, nonenhancing lesion located in the ventral middle cranial fossa. Histopathological examination was consistent with hypothalamic neuronal hamartoma. This is the first report describing clinical, imaging, and histopathological features of a hypothalamic neuronal hamartoma in a dog. These findings are compared with the human counterparts.

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The kallikrein-kinin system as mediator in vasogenic brain edema

Journal of Neurosurgery ◽

10.3171/jns.1986.64.2.0269 ◽

1986 ◽

Vol 64 (2) ◽

pp. 269-276 ◽

Cited By ~ 85

Author(s):

Andreas Unterberg ◽

Claudia Dautermann ◽

Alexander Baethmann ◽

Werner Müller-Esterl

Keyword(s):

Brain Edema ◽

Vasogenic Edema ◽

Specific Inhibition ◽

Kinin System ◽

Content Type ◽

Cold Lesion ◽

Highly Active ◽

Mediator Role ◽

Kallikrein Kinin System ◽

The Brain

✓ Evidence has previously been provided that administration of kinins to the cerebrum causes edema and opening of the blood-brain barrier. It has further been shown that these highly active compounds are formed in the brain under pathophysiological conditions. Their formation was enhanced when cerebral blood flow became compromised by an increase in intracranial pressure. Final evidence, however, was not available as to whether specific inhibition of the kallikrein-kinin (KK) system has a therapeutic function in acute head injury. The authors have demonstrated in rabbits that inhibition of the activating enzyme kallikrein by aprotinin or by aprotinin plus soybean trypsin inhibitor (SBTI), which interfere with plasma and tissue kallikrein, is associated with a decrease in formation of posttraumatic swelling after a standardized cold lesion to the brain. Saline-treated control animals with cerebral cold-induced injury had an increase in hemispheric weight 24 hours later of 13.0% ± 0.8% (standard error of the mean) in the damaged hemisphere compared to the contralateral nondamaged hemisphere. Administration of aprotinin or aprotinin plus SBTI led to a significant reduction of hemispheric swelling of 10.1% ± 0.7% or 10.4% ± 0.7%, respectively. In animals receiving SBTI only, hemispheric swelling evolving from cold injury was not significantly reduced. Therapeutic reduction of brain edema by aprotinin cannot be attributed to a nonspecific effect on the blood pressure, which in the experimental groups remained almost normal as compared to the control animals. Failure of SBTI to influence posttraumatic brain swelling may have resulted from disturbances in intravascular coagulation. Measurements of aprotinin in plasma and tissue demonstrate that the inhibitor doses employed are within an effective therapeutic range. Attenuation of brain edema by specific inhibition of the KK system provides evidence for a mediator role of kinins in vasogenic edema. Clinical trials with inhibitors of the KK system in acute forms of traumatic lesions associated with vasogenic edema appear worthwhile.

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