Vacuolation Of Neuropil Research Articles

Studies on the sequential pathology of Kyasanur Forest Disease (KFD) in Mouse brain: KFD virus induces apoptosis of neurons in cerebrum and hippocampus.

The sequential pathology of Kyasanur forest disease (KFD) in mouse brain was assessed in this study. Kyasanur forest disease virus (KFDV) strain P9605 used in this study was confirmed by real-time reverse transcriptase-polymerase chain reaction targeting the NS5 gene. Mouse Lethal Dose 50 (MLD50) of the virus was determined by in-vivo mice inoculation test. One MLD50 of the KFDV was inoculated intra-cerebrally into 36 mice aged 2-3 weeks. Another group of 36 age-matched mice that served as control group were inoculated with plain media. Six mice each from infected and control groups were euthanized every 24 hrs intervals for six days. Brain tissues were collected in 10% NBF. The collected brain tissues were processed and subjected to histopathological studies by Hematoxylin and Eosin staining. Grossly, the infected mice showed symptoms of dullness, hunched back appearance, weakness, sluggish movements with indication of hind quarter paralysis on day four post-infection. These symptoms got aggravated with complete paralysis of the hind quarters, inability to move and death on 5th and 6th day post-infection. Microscopically, the brain showed apoptosis of neurons, perivascular cuffing, gliosis, congestion, neuropil vacuolation, meningitis, degeneration, and necrotic neurons. The real-time RT-PCR on hippocampus of the KFDV-infected mouse brain showed three-fold higher expression levels of Caspase 3, a crucial mediator of apoptosis. The cerebral cortex, cerebellum and hippocampus that control the motor neuron activities and muscle tone were primarily affected, possibly correlating with the gross symptoms of hind quarter paralysis, ataxia, and other motor neuron dysfunctions noticed. Taken together, these findings reveal that KFDV induces apoptosis of neurons in the cerebrum and hippocampus of KFDV infected mice. Further studies are needed to confirm if the lesions noticed in mice brain simulate the brain lesions in humans since gross motor-neuron symptoms are similar in mice as well as humans.

Innate and adaptive immune gene expression in the brain is associated with neuropathological changes after infection with bovine alpha-herpesvirus-5 in mice

Bovine alpha herpesvirus-5 (BoAHV-5) is related to the development of meningoencephalitis in cattle. Very little is known about the molecular pathways involved in the central nervous system (CNS) damage associated with inflammation during BoHV-5 infection in mice. To better identify the specific immunological pathways triggered by BoAHV-5 infection in mice, we evaluated the mRNA expression of 84 genes involved in innate and adaptive immune responses. We compared gene expression changes in the cerebrum from noninfected and infected mice with BoHV-5 at a 1 × 107 TCID50. Then, we analyzed the association of these genes with neurological signs, neuropathology, and activation of glial cells in response to BoHV-5 infection. Three days after BoAHV-5 infection, increased expression of TNF, IL-2, CXCL10, CXCR3, CCR4, CCL5, IFN-γ, IL-10, IRF7, STAT1, MX1, GATA 3 C3, LIZ2, caspase-1 and IL-1b was found. We also observed the upregulated expression of the CD8a, TBX21 and CD40LG genes and the downregulated expression of the CD4 gene after BoAHV-5 infection. In addition, BoHV-5-infected animals showed higher levels of all the evaluated inflammatory mediators (TNF, IFN-γ and IL-10) on day 3 postinfection. BoAHV-5-infected animals showed neurological changes along with meningoencephalitis, neuropil vacuolation, hemorrhage and reactive gliosis. Astrogliosis and microgliosis, indicated by increased expression of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba-1), were found throughout the neuropil in infected brains. Moreover, cleaved caspase-3 immunopositive glio-inflammatory cells were visualized around some blood vessels in areas of neuroinflammation in the cerebrum. In agreement on that we found higher cleaved caspase-3 and Iba-1 expression evaluated by western blot analysis in the brains of infected mice compared to control mice. In conclusion, our results revealed

Porcine Forebrain Vacuolization Associated with Wasting in Pigs: A Novel Pathological Outcome Associated with Vitamin-Mineral Deficiency?

The term wasting refers to a clinical sign used to describe a physical condition characterized by growth retardation, usually of multifactorial origin. The objective of the present study was to describe for the first time a pathological process characterized by forebrain neuropil vacuolization in pigs showing wasting without conspicuous neurological signs. To characterize the lesions pathologically, affected and non-affected pigs from eight of these farms were investigated. Histologically, the most consistent lesion was neuropil vacuolization of the prosencephalon, mainly located in the thalamic nuclei and in the transition between the white and grey matter of the neocortex (40/56 in sick and 4/30 in healthy pigs). In the most severe cases, the vacuolation also involved the midbrain, cerebellar nuclei and, to a lesser extent, the medulla oblongata. Vacuolization of the forebrain was associated with pigs experiencing marked emaciation and growth retardation. Although the specific cause of the present case remained unknown, the preventive use of multivitamin and mineral complexes in drinking water ameliorated the condition, strongly suggesting a metabolic origin of the observed condition.

Naturally occurring histological findings and Alzheimer's-like pathology in the brain of aging African green monkeys (Chlorocebus sabaeus).

Nonhuman primates (NHPs) are important to study the pathophysiology of neurodegenerative disease and evaluate therapies targeting the central nervous system (CNS). Understanding the age-associated incidence of natural CNS pathology in a given NHP species is critical to assess the safety of potential treatments for neurodegenerative disorders like Alzheimer's disease (AD). We describe background and age-related neuropathology in the St. Kitts African green monkey (AGM), a recognized translational model for neurodegenerative research, additionally defining the age progression of AD-associated neuropathology in this species. Seventy-one AGM brains were examined, representing age groups of 3-6years (n=20), 7-9years (n=20), 10-15years (n=20), and >15years (n=11). A subset of brains (n=31) was assessed immunohistochemically for AD-related pathology, including expressions of Aβ, tau, and GFAP. Age-related microscopic findings included hemosiderosis, spheroid formation, neuronal lipofuscinosis and neuromelanosis, white matter and neuropil vacuolation, astrocytosis, and focal microgliosis. Non-age-related findings included perivascular ceroid-laden macrophages, meningeal melanosis, and vascular mineralization. Immunohistochemistry revealed 4G8-immunopositive Aβ plaques and vascular deposits in the prefrontal, frontal, cingulate, and temporal cortices of nine animals over 15years of age, with associated increase in GFAP expression. In 12 animals, 11 over the age of 10years, phosphorylated tau CP13-immunoreactive neurons, neuropil, and oligodendrocyte-like cells were seen in the prefrontal, frontal, cingulate, orbital, temporal, and entorhinal cortices as well as the hippocampus; no neurofibrillary tangles were observed. AD-related pathology showed an age-related development in cognitive-associated areas in the AGM, highlighting the value of the AGM as a natural model for these neurodegenerative diseases.

The internal ribosome entry site determines the neurotropic potential of enterovirus A71

The mechanisms underlying tissue-specific replication of enteroviruses are currently unclear. Although enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16) are both common pathogens that cause hand-foot-mouth disease, they display quite different neurotropic properties. Herein, we characterized the role of the internal ribosome entry site (IRES) in determining neurovirulence using an oral inoculation model of EV-A71. The receptor transgenic (hSCARB2-Tg) mice developed neurological symptoms after being infected with a mouse-adapted EV-A71 strain (MP4) via different administrative routes. Intragastric administration of the MP4 strain caused pathological changes such as neuronal loss and neuropil vacuolation, whereas replacing EV-A71 IRES with CV-A16 abolished the neuropathological phenotypes. The attenuated neurotropic potential of IRES-swapped EV-A71 was observed even in mice that received intraperitoneal and intracerebral inoculations. Fewer chimeric MP4 viral RNAs and proteins were detected in the mouse tissues, regardless of the inoculation route. Tissue-specific replication can be reflected in cell-based characterization. While chimeric MP4 virus replicated poorly in human intestinal C2BBe1 and neuroblastoma SH-SY5Y cells, its replication in susceptible rhabdomyosarcoma cells was not affected. Overall, our results demonstrated that the IRES determined the neurotropic potential of EV-A71 and CV-A16, emphasizing the importance of the IRES in tissue tropism, along with the host receptors.

Protective effects of evening primrose oil on behavioral activities, nigral microglia and histopathological changes in a rat model of rotenone-induced parkinsonism

Parkinson’s disease (PD) is a neurodegenerative illness described as damage to dopaminergic neurons. There is increasing evidence that neuroinflammatory activity mediated by microglia is extensively involved in the initiation and development of PD. This study assessed the protective effect of evening primrose oil [EPO] as an anti-inflammatory mediator in rotenone-induced Parkinsonism in rats. Forty-eight adult male albino rats were distributed into four groups. Group I: control. Group II: rotenone [1.5 mg/kg/48 h] was administered subcutaneously to the rats. Groups III and IV: the rats had rotenone plus daily oral [EPO] 5 and 10 mg/kg respectively. After 24 days, motor behaviour was assessed by the open field and rotarod tests. The brain striata were isolated and tested for tumor necrosis factor (TNF)-α, interleukin 6, NF-B [nuclear factor-kappa B], and dopamine levels. The mid-brain tissues were processed for light and electron microscopy examinations, and immunohistochemical staining for tyrosine hydroxylase [TH], and microglia cells' markers: [CD68 and IBA1]. Results revealed that rotenone-treated rats had poor motor function, a significantly increased striatal level of inflammatory markers, markedly shrunken neurons, degeneration, pyknotic neuroglia, neuropil vacuolation, markedly destructed swollen mitochondria with loss of their cristae, and dilated rough endoplasmic reticulum, as well as decreased TH and increased CD68 and IBA1-positive cells. Treatment with EPO ameliorates all the neuropathological changes of rotenone in the rat brain. In conclusion, EPO enhanced the motor performance, reduced the inflammatory marker levels, restored dopamine levels, and ameliorated the neurohistopathological lesions of rats with experimental parkinsonism, suggesting its neuroprotective and anti-inflammatory effects.

Status of Expression of GnRH gene in Fed, Starved, and Refed Clarias Gariepinus (African Catfish)

Inadequate nutritional status impairs gonadal activities, which may induce reproductive difficulties in Clarias gariepinus. This research was aimed at evaluating the influence of starvation and subsequent refeeding on the expression of GnRH gene in Clarias gariepinus. One hundred and eighty (180) healthy juvenile Clarias gariepinus (African catfish) used in this study were randomly placed into two groups in triplicates. Fish in the control group were fed to satiation while fish in the treatment group were starved and refed and the fish in the control group were continuously fed. Brain tissue samples were collected after 7 days and 14 days of starvation, histopathology, and gene expression studies were done. The histological sections of brain tissue of week one starved and fed, C. gariepinus show neuronal cells on a background of neuropil while week two starved reveal badly distorted morphological architecture and degenerated neuronal cells. However, the week two re-fed, C. gariepinus brain tissue shows vacuolation of neuropil while the week two continuous fed shows no abnormalities. No mortality was recorded during starvation and the entire experimental period. In the second week of starvation, a decrease in the fold change (1.7) was observed when compared to week one while the fold change (1.2) observed in week three (week one of re-fed) is lower than the fold change observed in week one and two of starvation. The fold change (1.7) observed in week four (week two re-fed) is higher than the fold change observed in week three. The highest fold change (2.13) was observed in week one of starvation while the lowest fold change (1.24) was observed in week one of re-feeding. This study reveals that exposure of C. gariepinus to prolonged food deprivation alters the expression of GnRH, which might lead to impairment in the reproductive success of Clarias gariepinus.

Astrocytes profiling in acute hepatic encephalopathy: Possible enrolling of glial fibrillary acidic protein, tumor necrosis factor-alpha, inwardly rectifying potassium channel (Kir 4.1) and aquaporin-4 in rat cerebral cortex.

Hepatic encephalopathy (HE) is a neurological disarray manifested as a sequel to chronic and acute liver failure (ALF). A potentially fatal consequence of ALF is brain edema with concomitant astrocyte enlargement. This study aims to outline the role of astrocytes in acute HE and shed light on the most critical mechanisms driving this role. Rats were allocated into two groups. Group 1, the control group, received the vehicle. Group 2, the TAA group, received TAA (300 mg/kg) for 3 days. Serum AST, ALT, and ammonia were determined. Liver and cerebral cortical sections were processed for hematoxylin and eosin staining. Additionally, mRNA expression and immunohistochemical staining of cortical GFAP, TNFα, Kir4.1, and AQP4 were performed. Cortical sections from the TAA group demonstrated neuropil vacuolation and astrocytes enlargement with focal gliosis. GFAP, TNFα, and AQP4 revealed increased mRNA expression, positive immunoreactivity, and a positive correlation to brain water content. In contrast, Kir 4.1 showed decreased mRNA expression and immunoreactivity and a negative correlation to brain water content. In conclusion, our findings revealed altered levels of TNFα, Kir 4.1, GFAP, and AQP4 in HE-associated brain edema. A more significant dysregulation of Kir 4.1 and TNFα was observed compared to AQP4 and GFAP.

Dietary Feeding Lycopene, Citric Acid, and Chlorella Alleviated the Neurotoxicity of Polyethylene Microplastics in African Catfish (Clarias gariepinus)

A few studies assessed how natural products can protect fish from the neurotoxic effects of Microplastics (MPs). Therefore, the goal of this study was to look into the neurotoxicity of PE-MPs on the brain tissue of African catfish (C. gariepinus), and whether dietary feeding on Chlorella, citric acid, and lycopene could help alleviate their toxicity. Five groups of fish were used: The first group received a standard diet (control). The second group was fed 500 mg/kg PE-MP. The third group was fed PE-MP + lycopene (500 mg/kg diet). The fourth group was fed PE-MP + citric acid (30 g/kg diet). And the fifth group was fed PE-MP + Chlorella (50 g/kg diet) for 15 days. The activities of Acetylcholinesterase (Ach), Monoamine Oxidase (MAO), Aldehyde Oxidase (AO), and Nitric Oxide (NO), and the histological effect on brain tissues were then assessed. The activity of the four neurological biomarker enzymes investigated was altered significantly in fish subjected to PE-MP alone compared with the control group. For fish exposed to PE-MP with lycopene, citric acid, or Chlorella, the activities of these neurological enzymes significantly improved particularly with Chlorella compared with fish fed PE-MP individually. Histological investigations illustrated that being subjected to PE-MPs effected cellular alterations in the telencephalon, including diffuse distorted and degraded neurons, encephalomalacia, aggregated neuroglial cells (gliosis), as well as deformed and necrotic neurons, neuropil vacuolation (spongiosis), aggregated neuroglial cells (gliosis), pyknotic neurons, and shrunken Purkinje cells which were found in the cerebellum. Most histological alterations induced by exposure to PE-MP feeding were restored by dietary feeding on Chlorella, citric acid, and lycopene. Accordingly, this study recommends using citric acid, lycopene, and Chlorella as a natural remedy against MP neurotoxicity particularly with Chlorella.

THE NEUROPROTECTIVE EFFECT OF CURCUMIN AGAINST TARTRAZINE-INDUCED NEUROBIOCHEMICAL AND HISTOPATHOLOGICAL CHANGES IN THE GRAY MATTER OF MOTOR CORTEX OF BRAIN OF SPRAGUE DAWLEY RATS

Objective: To study the neuroprotective effect of curcumin against tartrazine-induced neurobiochemical and histopathological changes in the gray matter of motor cortex of rat brain.
 Study Design: Lab-based experimental study.
 Place and Duration of Study: Department of Anatomy, Islamic International Medical College, from Sep 2019 to Sep 2020.
 Methodology: Forty five adult male albino rats (250-300 gm) were divided randomly into three groups (n=15). Group A, rats were given standard rat diet. Group B, rats were given tartrazine orally by dissolving in tap water in the dose of 7.5 mg/kg body weight. Group C, rats were given 200 mg/kg of curcumin along with tartrazine orally by dissolving in tap water, daily for 28 consecutive days. At the end, all animals were dissected and their brain were removed. The neurobiochemical parameters including lipid peroxidation marker level along with microscopic changes widening of Virchow’s robin space and neuropil vacuolation in neurovascular unit were observed. Results were analyzed using SPSS version 21.
 Results: The curcumin administration significantly improved the MDA levels (p-value <0.001 on intergroup comparison) and widening of Virchow’s robin space (group A=3.57 ± 0.78 µm, group B=19.39 ± 0.68 µm, group C12.1 ± 0.83 µm; p-value <0.001). Neuropil vacuolation was reduced to negligible in 60% rats of curcumin treated group.
 Conclusion: Curcumin displayed a neuroprotective role in improving the tartrazine induced neurobiochemical and histopathological changes in the motor cortex of rat brain.

Cerebral cortex alterations induced via sub-acute exposure of albino rat to fipronil insecticide (Histopathological and immunohistochemical study)

Fipronil (FIP) is a globally utilized insecticide that leads to environmental pollution. Exposure of non-target organisms to FIP causes occupational and non-occupational neurological hazard. Therefore, this study aimed to assess the histopathological and immunohistochemical changes in the cerebral cortex of adult albino rats exposed to FIP. Twenty adult male albino rats were divided into 2 groups: control and experimental groups. Each rat of the experimental group received a daily oral dose of FIP at 10 mg /kg body weight. After 45 days of FIP daily administration, samples from the cerebral cortex were collected from both groups and were processed for histopathological and immunohistochemical examination. The cerebral cortex of treated rats showed severe neuronal degeneration, reactive gliosis, neuropil vacuolation and elevated immunoreactivity to GFAP, iNOS and Caspase 3 (active form). In conclusion, sub-acute FIP exposure has neurotoxic effect that appeared in our study in the form of apoptosis and tissue reactivity of the cerebral cortex.

Protective effect of propolis on manganese chloride neurotoxicity of olfactory bulb in adult male albino rat.

Manganese (Mn) is widely used for industrial purposes and exposure to high levels of Mn may cause an irreversible brain disease. Propolis is a natural plant product; it acts as a powerful reactive oxygen species scavenger and improves the neurodegeneration process. In this study 40 adult male albino rats were divided randomly into four groups 10 rats each: group I (control group), group II manganese chloride (MnCl2) received 10 mg/kg/day/orally for 4 weeks by intra-gastric tube, group III (propolis group) received 50 mg/kg/day/orally for 4 weeks by intra-gastric tube, and group IV (MnCl2 + propolis group) received the same doses with the same duration and route as in groups II and III. Rats were sacrificed after 24 h of last dose. The olfactory bulbs removed, the right bulb cut to be processed for haematoxylin and eosin, immunohistochemical staining and the left cut for electron microscopic studies. Results revealed that rat olfactory bulb from MnCl2 group showed darkly stained mitral cells with dark pyknotic nuclei, some show pericellular spaces and vacuolation, dark apoptotic cells in granular cells, neuropil vacuolation and pyknotic astrocyte. Electron microscopic examination showed abnormal granular cell with irregular damaged nuclear membrane, rupture of myelin fibre. Mitral nerve cell with destructed nucleus, many cytoplasmic vacuoles, swollen rough endoplasmic reticulum, vacuolated mitochondria and neuropil were observed. Manganese chloride + propolis group showed improvement compared to MnCl2 group. It was concluded that propolis can ameliorate the toxic changes of manganese chloride on rat olfactory bulb.

High levels of NGF during anxiety-like behavior in a murine model of brain ischemic stroke

PurposeNeuropsychiatric disorders following stroke, including depression and anxiety, are often associated with long-term disability. Neurotrophic factors play an important role in the pathophysiology of many neurodegenerative and neuropsychiatric disorders. In the current study, we investigated a potential participation of neurotrophic factors in stroke-associated behavioral and pathological changes 14 days after ischemia. MethodsTransient global cerebral ischemia was induced by bilateral occlusion of common carotid arteries (BCCAo) in C57BL/6 mice. Neurological evaluation was performed daily up to 14 days after induction. The Open Field (OF) and Elevated Plus Maze (EPM) tests were performed. After behavioral tests, brains from sham and ischemic mice were removed and processed to evaluate histopathology and immunomarcation for cleaved caspase-3 as well as the neurotrophic factors brain-derived neurotrophic factor (BDNF), glial cell line derived neurotrophic factor (GDNF), and neural growth factor (NGF) by ELISA. ResultsIschemic animals presented anxiety-like behavior and histopathological alterations mainly characterized by formation of small necrotic cavities surrounded by penumbra zone and neuropil vacuolation in the frontal cortex, ischemic neurons in the hippocampus and gliosis in the midbrain. Some immunopositive neurons for cleaved caspase-3 were observed in the penumbra by immunohistochemical analysis. Higher levels of NGF were found in the brain of BCCAo mice compared with sham animals. Similar concentrations of BDNF and GDNF were detected in both groups. ConclusionOur results suggested the participation of NGF in anxiety-like behavior at 14 days after induction of experimental cerebral ischemia and reperfusion.

First Case of Idiopathic Eosinophilic Meningoencephalitis in a Sheep

A 1.5-year-old ewe was presented with neurological signs that had been observed from about 2 days prior to death. There had been no clinical response to anti-inflammatory and antibiotic treatment. Histopathological examination of the brain revealed a severe and widespread eosinophilic meningoencephalomyelitis of unknown aetiology. Defining histological features included diffuse angiocentric eosinophilic infiltrates in the neuroparenchyma and meninges, neuronal necrosis, astrocytosis, neuropil vacuolation and occasional glial scars. Differential diagnostics for eosinophilic meningoencephalitis were taken into account and investigated by means of special stains, immunohistochemistry, bacteriology and polymerase chain reaction. No pathological changes or ancillary tests were supportive or revealed a specific aetiology for the condition and therefore it was considered idiopathic. Idiopathic meningoencephalitis is a rare disease, mainly described in man and rarely in dogs, with no apparent aetiological cause or potential breed predisposition. To our knowledge this is the first case of idiopathic eosinophilic meningoencephalitis in a sheep and provides a histopathological guideline for prospective comparative pathology studies.

Lead Poisoning in Cattle Held in a Military Training area

Background: Lead poisoning is one of the major toxic diseases of cattle. Contamination occurs with ingestion of products containing lead, especially batteries, or through contaminated pastures and water sources. Clinical signs are neurological and necropsy findings and histopathological changes may vary depending on the clinical presentation. Although the diseaseis widely reported in the literature, there are rare descriptions of intoxication in cattle raised in military training areas. This work describes the epidemiological, clinical and anatomopathological features of an outbreak of lead poisoning in cattle kept in a military artillery training camp.Case: Fifteen cattle out of a herd of sixty 4-6 year-old, mixed breed castrated males were affected. The cattle were held in a 100 ha of native pasture used for military artillery training. After three weeks in this area, the affected cattle had predominantly neurological clinical manifestations, characterized by somnolence, ambulatory incoordination, muscle tremors,bruxism, aimless walking, blindness and decubitus. The clinical course was 24-72 h. Eight of the 15 affected cattle died and two were necropsied. Necropsy finds were non-specific and the histological lesions of both necropsied cattle were restricted to the brain and kidneys. Laminar neuronal necrosis, neuropil vacuolization (spongiosis) and vascular endothelial hypertrophy were observed in the telencephalic cortex. Additionally there was astrocytic degeneration and neuronophagia.There was degeneration and necrosis of renal tubular epithelium and in one bovine there were intranuclear inclusion bodies in the renal epithelial cells; these inclusion bodies were highlighted using both modified Ziehl-Neelsen and periodic acid Schiff (PAS) stains. The levels of lead found in the kidneys and livers of the two necropsied cattle were respectively51.7 μg/g and 41.00 μg/g for one of the necropsied cattle; and 431μg/g and 39.0 μg/g for the other. After the diagnosis of intoxication, cattle were removed from the area and the remaining seven affected bovines recovered.Discussion: The diagnosis of lead poisoning in cattle in the current study was based on epidemiological, clinical, anatomopathological data and in the determination of lead levels in the kidney and liver. The association of these data provides an invaluable aid in confirming a presumptive diagnosis of lead poisoning. Pasturing on military artillery training fieldsis a rarely described form source of lead for the intoxication in bovine species. In such cases, cattle may ingest the lead directly from the soil or through contaminated pastures containing lead dust on the surface of the leaves. Histologically, laminar neuronal necrosis in the telencephalic cortex, associated with tubular necrosis and intranuclear inclusion bodies intubular epithelial cells, are characteristic features of the intoxication. These changes are usually associated with ischemic anoxia in the nervous system and alteration in nuclear function which interferes in gene expression in the kidney. Lead poisoning in cattle should be differentiated from other neurological conditions, especially rabies, hepatic encephalopathyand several causes of polioencephalomalacia. Areas of military artillery training are unfit for the development of agricultural exploitation activities, as they represent potential sources of contamination for livestock.Keywords: diseases of cattle, toxicology, heavy metal, polioencephalomalacia.

THE AMELIORATING ROLE OF Alpha-LIPOIC ACID SUPPLMENTATION ON ADVERSE EFFECTS INDUCED BY LEAD ACETATE IN BOTH THE HIPPOCAMUS AND THE CEREBRAL CORTEX OF THE MALE ALBINO RATS

The present study focused on two brain areas hippocampus and the cerebral It was designed to investigate the possible mechanisms involved in Lead acetate neurotoxicity and the potential protective effects of α-lipoic acid (α-LA), as an antioxidant against lead-induced neurotoxicity. Fourty adult male albino rats Rattus rattus (each weighing 130 ± 10 g) were divided into four groups (n=8): 1- Normal control group; C: Normal male rats fed ad libitum and allowed a free access of water, and were kept without any treatments. 2- Initiation group (lead-acetate control group; A): Normal male rats received Lead acetate in an interperitoneal dose of 20 mg/kg b.wt daily for two weeks. 3- Treatment group (α-lipoic acid control group; B): Normal male rats were intraperitoneally injected with α-lipoic acid in a dose of 20 mg/kg b.wt daily for three weeks. 4- Pre-initiation treatment group (prophylactic group; D): Normal male rats were intraperitoneally injected with α-Lipoic acid in a dose of 20 mg/kg b.wt daily for one week and then received the above-mentioned dose of the lead acetate for other two successive weeks together with the same dose of α-lipoic acid. 5- Post-initiation treatment group (therapeutic group; E): Normal male rats were intraperitoneally injected once daily with lead acetate (20 mg/kg b.wt) for two weeks then were intraperitoneally injected with α-lipoic acid in a dose of 20 mg/kg b.wt daily for successive three weeks. The levels of lipid peroxidation as malondialdehyde (MDA), protein carbonyl content (PCC), reduced glutathione (GSH), nitric oxide level (NO), and serotonin (5- HT) were estimated in the selected brain regions, the hippocampus and the cerebral cortex, of adult male albino rats in the different groups. These biochemical variables were supported by histopathological examinations by using H&E and toluidine blue staining. Results showed that administration of lead acetate led to enhancement of lipid peroxidation and increased PCC with a concomitant reduction in GSH levels and NO production. In addition, the levels of 5-HT decreased in the hippocampus and the cerebral cortex. However, the administration of α-LA showed a protective effect against Lead acetate-induced neurotoxicity. Rats treated with α-LA showed a corresponding decrease in lipid peroxidation and PCC level. Furthermore, there was an increase in brain GSH level, NO production and level of 5-HT in both brain regions hippocampus and the cerebral Histological studies showed that Lead acetate caused different degrees of neuronal degeneration, focal gliosis, pyknotic neurons, oedema in meninges, cerebral neuropil vacuolization and degenerations. The rats treated with α-lipoic acid revealed an improvement in the histopathological alterations induced by Lead acetate. Finally, the data showed that α-LA has an effect when administered as a therapeutic drug more than as a prophylactic one.

STUDY OF CHRONIC TOXIC EFFECT OF DELTAMETHRIN AND DIMETHOATE ON BRAIN OF ADULT MALE ALBINO RATS

organophosphate pesticides are being increasingly used in combination with Pyrethroids. The effects of single molecules are being studied, but the risk associated with pesticide mixtures is still to estimate. So, the purpose of the current study was to evaluate the individual and combined toxic effects of deltamethrin (DLM) and dimethoate (DM) on brain of adult male albino rats. For this purpose, 60 adult male albino rats were randomized into 5equal groups: Group I: negative control, Group II: positive control received 1ml corn oil once daily. Group III received deltamethrin (5 mg/kg b.w./orally ∕daily), Group IV received dimethoate (20 mg/kg b.w./ orally ∕daily), Group V received deltamethrin (5 mg/kg b.w) and dimethoate(20 mg/kg b.w)orally ∕daily . At the end of the study (12 weeks); Body weight was evaluated then blood sample were obtained for estimation of oxidative stress markers malondialdehyde (MDA) glutathione (GSH), total antioxidant capacity TAC) and plasma cholinesterase (PCHE) level then rats were sacrificed. The brains were excised, prepared for histopathological, immunohistochemical examination and DNA damage estimation by comet assay. Results revealed that single DLM and DM exposure significantly had adverse effects on adult male Albino rats in the form of decrease in the body weight, increase in brain &serum MDA, decrease in TAC &GSH and decrease in PCHE level. Pathological changes in brain of rats included, pychnosis, neuronal degeneration, neuropil vacuolization, hemorrhage and congested blood vessels beside positive immuoreaction for bax. Also they caused DNA damage compared to control group. In conclusion, chronic exposure to DLM and DM singly and in combination induced significant oxidative damage in rat brain, associated with marked perturbations in antioxidant defense system in addition to genotoxicity detected by comet assay. Also, the mixture of the two pesticides caused greater damage on the brain of male albino rats, than the individual pesticides.

Detection of drought tolerance gene(s) from some Egyptian wheat cultivars

Acetaminophen is a safe analgesic and an antipyretic agent that is available without a prescription. However, high doses of acetaminophen are a direct cause of hepatic toxicity, neurotoxicity, and even death through induction of oxidative stress. The study aimed to evaluate the possible prophylactic and therapeutic effects of nicotinamide (500 mg/kg B.W.) on the behavioral changes examined by forced swim test and open field test, as well as on the antioxidants status in the brain of male Wistar rats that were intoxicated with a single overdose of acetaminophen (5 g/kg B.W.). Acetaminophen showed depressant like behavior, impaired locomotor activity, induced oxidative damage and neurotoxicity through elevation of lipid peroxidation level, reduction of glutathione level, glutathione peroxidase and catalase activities. On the other hand, nicotinamide showed an obvious antidepressant-like effect in the forced swim test in the acetaminophen-intoxicated rats and treated with nicotinamide either in prophylactic or therapeutic ways. However, nicotinamide increased motor deficits and impaired antioxidants status. Neurohistology of the cerebellum showed neuropil vacuolation, and degenerating Purkinje cells with pyknotic nuclei in groups treated with acetaminophen, nicotinamide or both together. In conclusion, caution must be taken upon administration of overdoses of nicotinamide due to its potential neurotoxicity, particularly, upon combination with acetaminophen therapy.

Potential risks of maternal administration of Mucophylline on the pups of albino rats during lactation

The present study was undertaken to evaluate the potential risks of the mucolytic and broncholytic drug, Theophylline derivatives (Mucophylline) maternally administered on the pups. The nursing rats orally administered from 1st postpartum day (PPD) to 21th PPD with two different doses 30.83mg/kg (low dose) and 66.61mg/kg (Human equivalent dose (HED)). On the 21th PPD, the postnatal developmental signs, skeletal malformation and the histopathology of neonatal liver, kidney and brain were examined. Our results showed that Mucophylline induced a significant reduction in the neonatal weight and length, delayed, weak and incomplete ossification, wavy ribs and the neonatal liver revealed histopathological changes, pyknotic hepatocytes, cytoplasmic vacuolization, dilated sinusoid and necrotic area. Kidney revealed alternation changes, enlargement of the glomerulus, renal tubules degeneration and lymphatic infiltration. Brain (cerebral cortex and cerebellum) showed neurodegenerative changes, vacuolization of neuropil, congested and dilated blood vessel and dark stain neurons. Our results showed that the activities of non-enzymatic (GSH) and enzymatic (GST, CAT) antioxidants were insignificantly decrease in both neonatal brain and liver tissues of rats administered with 30.83mg/kg and 61.66mg/kg of Mucophylline and insignificant increase in MDA levels in both neonatal brain and liver tissues. However, significant reduction (P≤0.05) in the content of GR was recorded in neonatal brain tissue of rats administered with 30.83mg/kg and 61.66mg/kg of Mucophylline during lactation period in comparison with control. These support and proof the potential risks of the maternal administration of Mucophylline on pups.

Atypical scrapie in Australia.

Since its initial detection in Norway in 1998, atypical scrapie ('atypical/Nor98 scrapie') has been reported in sheep in the majority of European countries (including in regions free of classical scrapie) and in the Falkland Islands, the USA, Canada, New Zealand and Australia. The diagnosis in Australia of atypical scrapie in four Merino and one Merino-cross sheep showing clinical signs of neurological disease was based on the detection of grey matter neuropil vacuolation (spongiform change) in the brain (particularly in the molecular layer of the cerebellar cortex) and associated abnormal prion protein (PrPSc ) deposition in both grey and white matter. Changes were minimal in the caudal brainstem, the predilection site for lesions of classical scrapie. The distinctive lesion profile of atypical scrapie in these five sheep highlights the diagnostic importance of routine histological evaluation of the cerebellum for evidence of neuropil vacuolation and associated PrPSc deposition in adult sheep with suspected neurological disease.