James O. Olopade

The Mechanism of Vanadium-Mediated Developmental Hypomyelination Is Related to Destruction of Oligodendrocyte Progenitors Through a Relationship with Ferritin and Iron

The second post-natal week in rat is the period of the most intense oligodendrocyte development and myelination. This period coincides with peak iron import by oligodendrocytes. During that time oligodendrocyte progenitors (OPCs) are sensitive to agents that may disturb normal iron homeostasis and assimilation of iron into these cells. One mechanism by which iron homeostasis can be disrupted is by environmental exposure to other metals. Vanadium is a transition metal, and exposure to vanadium during early brain development produces hypomyelination with variety of related neuro-behavioral phenotypes. In the current study, we investigated mechanisms of hypomyelination induced by vanadium exposure in developing rat brain. We demonstrate that both in vivo and in vitro, OPCs are more sensitive to vanadium exposure than astrocytes or mature oligodendrocytes. Vanadium exposure in OPCs resulted in increased ROS generation and increased annexinV labeling suggestive of apoptosis. Because ferritin is a major iron delivery protein for oligodendrocytes, we exposed the cells to recombinant ferritin and iron both of which exacerbated vanadium cytotoxicity, while the iron chelator desferroxamine (DFO) prevented cytotoxic/apoptotic effects of vanadium. To illustrate relationship between ferritin and vanadium, we demonstrate that vanadium exacerbated DNA nicking produced by iron-rich spleen ferritin, but not iron-poor apoferritin, resulting in a single and double strand breaks in a DNA relaxation assay. We propose that developmental exposure to vanadium interferes with normal iron assimilation into oligodendrocytes resulting in oxidative stress and apoptosis. Therefore, depletion of OPCs due to vanadium exposure in early post-natal period may be an important mechanism of vanadium-induced hypomyelination.

Failure of recovery from lead induced hepatoxicity and disruption of erythrocyte antioxidant defence system in Wistar rats.

Lead acetate (PbA) is one of the major environmental contaminants with grave toxicological consequences both in the developing and developed countries. The liver and erythrocyte antioxidant status and markers of oxidative were assessed. Exposure of rats to PbA led to significant decline (p < 0.05) in hepatic and erythrocyte glutathione peroxidase (GPx), glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) content. Similarly, malondialdehyde (MDA) and H(2)O(2) concentrations were significantly (p < 0.05) elevated. Histopathology and immunohistology of liver of rats exposed to PbA showed focal areas of necrosis and COX-2 expression after 6 weeks of PbA withdrawal. Taken together, hepatic and erythrocytes antioxidant defence system failed to recover after withdrawal of the exposed PbA for the period of the study. In conclusion, experimental animals exposed to PbA did not recover from hepatotoxicity and disruption of erythrocyte antioxidant defence system via free radical generation and oxidative stress.

Some Aspects of the Clinical Anatomy of the Mandibular and Maxillofacial Regions of the West African Dwarf Goat in Nigeria

Fueron analizadas algunas medidas en la mandibula y maxila de treinta cabras enanas, del Oeste de Africa (WAD) sin desordenes esqueleticos aparentes. La longitud y altura de la mandibula fueron 12,0 cm y 6,9 cm, respectivamente. Las distancias desde la raiz alveolar lateral al foramen mental y desde este ultimo al margen inferior de la mandibula, fueron 1,56 cm y 2,58 cm, respectivamente. El ancho y altura del foramen mental fueron 0,5 cm y 0,3 cm, respectivamente. Estos datos son discutidos considerando las maniobras de aplicacion clinica realizadas en la cabeza de la cabra, como tambien con los procedimientos de anestesia regional durante la extraccion dental

Morphological and biochemical investigation into the possible neuroprotective effects of kolaviron (Garcinia kola bioflavonoid) on the brains of rats exposed to vanadium

In this study, the morphological and biochemical susceptibility of the rat brain to vanadium, in the form of sodium metavanadate, and the comparative ameliorative effect of Garcinia kola and kolaviron (G. kola extract), was examined. Brain regions examined were the cerebrum, cerebellum, hippocampus and the olfactory bulb. We showed that vanadium administration caused cellular vacuolation, congestion, and Purkinje cell degeneration and a marked reduction in myelin tracts. Biochemical tests revealed increased lipid peroxidation induced by vanadium, which was ameliorated with the administration of G. kola and kolaviron. Vanadium administration caused an increase in thiobarbituric acid–reactive substances (TBARS) in the cerebrum and hippocampus, whereas the administration of kolaviron resulted in a reduction of the TBARS level by 65.7 and 80%, respectively, in the regions aforementioned. Also, the administration of kolaviron resulted in an increased activity of superoxide dismutase (61.24%) in all brain regions assessed, when compared with the group administered vanadium alone. Results obtained from this study led to the conclusion that kolaviron reduces vanadium-induced oxidative stress in the brain.

Gene-environment interactions: Neurodegeneration in non-mammals and mammals

The understanding of how environmental exposures interact with genetics in central nervous system dysfunction has gained great momentum in the last decade. Seminal findings have been uncovered in both mammalian and non-mammalian model in large result of the extraordinary conservation of both genetic elements and differentiation processes between mammals and non-mammalians. Emerging model organisms, such as the nematode and zebrafish have made it possible to assess the effects of small molecules rapidly, inexpensively, and on a miniaturized scale. By combining the scale and throughput of in vitro screens with the physiological complexity and traditional animal studies, these models are providing relevant information on molecular events in the etiology of neurodegenerative disorders. The utility of these models is largely driven by the functional conservation seen between them and higher organisms, including humans so that knowledge obtained using non-mammalian model systems can often provide a better understanding of equivalent processes, pathways, and mechanisms in man. Understanding the molecular events that trigger neurodegeneration has also greatly relied upon the use of tissue culture models. The purpose of this summary is to provide-state-of-the-art review of recent developments of non-mammalian experimental models and their utility in addressing issues pertinent to neurotoxicity (Caenorhabditis elegans and Danio rerio). The synopses by Aschner and Levin summarize how genetic mutants of these species can be used to complement the understanding of molecular and cellular mechanisms associated with neurobehavioral toxicity and neurodegeneration. Next, studies by Suñol and Olopade detail the predictive value of cultures in assessing neurotoxicity. Suñol and colleagues summarize present novel information strategies based on in vitro toxicity assays that are predictive of cellular effects that can be extrapolated to effects on individuals. Olopade and colleagues describe cellular changes caused by sodium metavanadate (SMV) and demonstrate how rat primary astrocyte cultures can be used as predicitive tools to assess the neuroprotective effects of antidotes on vanadium-induced astrogliosis and demyelination.

Morphometric Investigation of the Brainof West African Dwarf Sheep in Nigeria

Se efectuo un estudio morfometrico en 20 encefalos frescos, congelados de ovejas enanas del Oeste africano. El peso promedio del cerebro fue de 69.14g, mientras que el largo y la altura fueron de 7.48cm y 4.17cm, respectivamente. La longitud promedio del cerebro y cerebelo de 5.08cm y 2.27cm, respectivamente. El peso relativo del encefalo fue 0,08%, mientras que el de la cabeza fue 0.8%. Hubo diferencias significativas (p< 0.05) en el peso de la cabeza, del encefalo, longitud y altura del cerebro y en el peso relativo del cerebro de los animales de mas de 10kg, si estos son comparados con animales de menor peso. Los valores de los primeros cuatro parametros fueron mas altos, en cambio el quinto fue mas bajo. Animales de un ano de edad y mas, tenian un cuerpo significativamente mas pesado y un cerebro de mayor longitud (p < 0.05) que aquellos bajo esta edad. Sin embargo, en estos ultimos fue significativo un peso relativo mas bajo para el encefalo y la cabeza. Los resultados obtenidos en este estudio pueden ser usados en Neuroanatomia Comparada y como base de datos en investigaciones de neuropatologia, farmacologia, anestesiologia y neurofisiologia

Memory Deficit Recovery after Chronic Vanadium Exposure in Mice.

Vanadium is a transitional metal with an ability to generate reactive oxygen species in the biological system. This work was designed to assess memory deficits in mice chronically exposed to vanadium. A total of 132 male BALB/c mice (4 weeks old) were used for the experiment and were divided into three major groups of vanadium treated, matched controls, and animals exposed to vanadium for three months and thereafter vanadium was withdrawn. Animals were tested using Morris water maze and forelimb grip test at 3, 6, 9, and 12 months of age. The results showed that animals across the groups showed no difference in learning but had significant loss in memory abilities after 3 months of vanadium exposure and this trend continued in all vanadium-exposed groups relative to the controls. Animals exposed to vanadium for three months recovered significantly only 9 months after vanadium withdrawal. There was no significant difference in latency to fall in the forelimb grip test between vanadium-exposed groups and the controls in all age groups. In conclusion, we have shown that chronic administration of vanadium in mice leads to memory deficit which is reversible but only after a long period of vanadium withdrawal.

Regional Myelin and Axon Damage and Neuroinflammation in the Adult Mouse Brain After Long-Term Postnatal Vanadium Exposure

Environmental exposure to vanadium occurs in areas of persistent burning of fossil fuels; this metal is known to induce oxidative stress and oligodendrocyte damage. Here, we determined whether vanadium exposure (3 mg/kg) in mice during the first 3 postnatal months leads to a sustained neuroinflammatory response. Body weight monitoring, and muscle strength and open field tests showed reduction of body weight gain and locomotor impairment in vanadium-exposed mice. Myelin histochemistry and immunohistochemistry for astrocytes, microglia, and nonphosphorylated neurofilaments revealed striking regional heterogeneity. Myelin damage involved the midline corpus callosum and fibers in cortical gray matter, hippocampus, and diencephalon that were associated with axonal damage. Astrocyte and microglial activation was identified in the same regions and in the internal capsule; however, no overt myelin and axon damage was observed in the latter. Double immunofluorescence revealed induction of high tumor necrosis factor (TNF) immunoreactivity in reactive astrocytes. Western blotting analysis showed significant induction of TNF and interleukin-1&bgr; expression. Together these findings show that chronic postnatal vanadium exposure leads to functional deficit and region-dependent myelin damage that does not spare axons. This injury is associated with glial cell activation and proinflammatory cytokine induction, which may reflect both neurotoxic and neuroprotective responses.

Osteometry of the skull of one-humped camels. Part I: immature animals

The aim of this study was to investigate osteometric indices of immature camels (2-3 years old) in Nigeria. The cranial length, viscerocranial length, maximum zygomatic width, neurocranial volume, skull and facial index for females and males were 22.1 cm and 22.3 cm; 16.3 cm and 16.7 cm; 15.8 cm and 16.1 cm; 479 ml and 496 ml; 40.9 and 41.3, and 96.4 and 96.2 respectively. The mean orbital horizontal and vertical diameters of young camels were similar to each other giving a near complete circular shape. The foramen magnum index was over 100 because of a relatively higher height than width. The data were compared with those of other types of immature camels in the literature and will be useful for anatomical, developmental, anthropological and clinical studies of camels.

Behavioural studies on the ethanol leaf extract of Grewia carpinifolia in Wistar rats.

BACKGROUND Grewia carpinifolia is a plant commonly used in the tropics to manage various central nervous system (CNS) disorders. However, despite its widespread use no scientific work has been reported to validate these claims. OBJECTIVES To evaluate the activity of G. carpinifolia as it affects behaviour using animal model. METHODS Twenty five adult Wistar rats were randomly divided into five groups (A-E). Group A served as control (given only distilled water), Groups B, C, D and E were administered with single oral dose of ethanol extract of G. carpinifolia leaf at 100, 200, 400 and 800 mg/kg body weight respectively for twenty eight days consecutively. Subsequently, open field test, negative geotaxis and hanging wire test were performed. Body and brain weights were measured and histological examination of the brain was also performed. RESULTS At the tested doses, the extract significantly increased the time spent on the hanging wire and decreased locomotor activity at 800 mg/kg. No significant difference was observed in body and brain weights of extract treated groups when compared with the control. No visible histological lesion was also observed. CONCLUSION The plant extract may improve muscular strength at tested doses and possess CNS depressant activity at 800 mg/kg.