Vanadium administration ameliorates cortical structural and functional changes in juvenile hydrocephalic mice.

Vanadium is a prevalent neurotoxic transition metal with therapeutic potentials in some neurological conditions. Hydrocephalus poses a major clinical burden in neurological practice in Africa. Its primary treatment (shunting) has complications, including infection and blockage; alternative drug-based therapies are therefore necessary. This study investigates the function and cytoarchitecture of motor and cerebellar cortices in juvenile hydrocephalic mice following treatment with varying doses of vanadium. Fifty juvenile mice were allocated into five groups (n = 10 each): controls, hydrocephalus-only, low- (0.15 mg/kg), moderate- (0.3 mg/kg), and high- (3.0 mg/kg) dose vanadium groups. Hydrocephalus was induced by the intracisternal injection of kaolin and sodium metavanadate administered by intraperitoneal injection 72hourly for 28 days. Neurobehavioral tests: open field, hanging wire, and pole tests, were carried out to assess locomotion, muscular strength, and motor coordination, respectively. The cerebral motor and the cerebellar cortices were processed for cresyl violet staining and immunohistochemistry for neurons (NeuN) and astrocytes (glial fibrillary acidic protein). Hydrocephalic mice exhibited body weight loss and behavioral deficits. Horizontal and vertical movements and latency to fall from hanging wire were significantly reduced, while latency to turn and descend the pole were prolonged in hydrocephalic mice, suggesting impaired motor ability; this was improved in vanadium-treated mice. Increased neuronal count, pyknotic cells, neurodegeneration and reactive astrogliosis were observed in the hydrocephalic mice. These were mostly mitigated in the vanadium-treated mice, except in the high-dose group where astrogliosis persisted. These results demonstrate a neuroprotective potential of vanadium administration in hydrocephalus. The molecular basis of these effects needs further exploration.

Attenuation of Vanadium-Induced Neurotoxicity in Rat Hippocampal Slices (In Vitro) and Mice (In Vivo) by ZA-II-05, a Novel NMDA-Receptor Antagonist.

Exposure to heavy metals, such as vanadium, poses an ongoing environmental and health threat, heightening the risk of neurodegenerative disorders. While several compounds have shown promise in mitigating vanadium toxicity, their efficacy is limited. Effective strategies involve targeting specific subunits of the NMDA receptor, a glutamate receptor linked to neurodegenerative conditions. The potential neuroprotective effects of ZA-II-05, an NMDA receptor antagonist, against vanadium-induced neurotoxicity were explored in this study. Organotypic rat hippocampal slices, and live mice, were used as models to comprehensively evaluate the compound's impact. Targeted in vivo fluorescence analyses of the hippocampal slices using propidium iodide as a marker for cell death was utilized. The in vivo study involved five dams, each with eight pups, which were randomly assigned to five experimental groups (n = 8 pups). After administering treatments intraperitoneally over six months, various brain regions were assessed for neuropathologies using different immunohistochemical markers. High fluorescence intensity was observed in the hippocampal slices treated with vanadium, signifying cell death. Vanadium-exposed mice exhibited demyelination, microgliosis, and neuronal cell loss. Significantly, treatment with ZA-II-05 resulted in reduced cellular death in the rat hippocampal slices and preserved cellular integrity and morphological architecture in different anatomical regions, suggesting its potential in countering vanadium-induced neurotoxicity.

GluN2A and GluN2B N-Methyl-D-Aspartate Receptor (NMDARs) Subunits: Their Roles and Therapeutic Antagonists in Neurological Diseases.

N-methyl-D-aspartate receptors (NMDARs) are ion channels that respond to the neurotransmitter glutamate, playing a crucial role in the permeability of calcium ions and excitatory neurotransmission in the central nervous system (CNS). Composed of various subunits, NMDARs are predominantly formed by two obligatory GluN1 subunits (with eight splice variants) along with regulatory subunits GluN2 (GluN2A-2D) and GluN3 (GluN3A-B). They are widely distributed throughout the CNS and are involved in essential functions such as synaptic transmission, learning, memory, plasticity, and excitotoxicity. The presence of GluN2A and GluN2B subunits is particularly important for cognitive processes and has been strongly implicated in neurodegenerative diseases like Parkinson's disease and Alzheimer's disease. Understanding the roles of GluN2A and GluN2B NMDARs in neuropathologies provides valuable insights into the underlying causes and complexities of major nervous system disorders. This knowledge is vital for the development of selective antagonists targeting GluN2A and GluN2B subunits using pharmacological and molecular methods. Such antagonists represent a promising class of NMDA receptor inhibitors that have the potential to be developed into neuroprotective drugs with optimal therapeutic profiles.

Neuropathological profile of the African Giant Rat brain (Cricetomys gambianus) after natural exposure to heavy metal environmental pollution in the Nigerian Niger Delta.

Pollution by heavy metals is a threat to public health because of the adverse effects on multiple organ systems including the brain. Here, we used the African giant rat (AGR) as a novel sentinel host to assess the effect of heavy metal accumulation and consequential neuropathology upon the brain. For this study, AGR were collected from distinct geographical regions of Nigeria: the rain forest region of south-west Nigeria (Ibadan), the central north of Nigeria (Abuja), and in oil-polluted areas of south Nigeria (Port-Harcourt). We found that zinc, copper, and iron were the major heavy metals that accumulated in the brain and serum of sentinel AGR, with the level of iron highest in animals from Port-Harcourt and least in animals from Abuja. Brain pathology, determined by immunohistochemistry markers of inflammation and oxidative stress, was most severe in animals from Port Harcourt followed by those from Abuja and those from Ibadan were the least affected. The brain pathologies were characterized by elevated brain advanced oxidation protein product (AOPP) levels, neuronal depletion in the prefrontal cortex, severe reactive astrogliosis in the hippocampus and cerebellar white matter, demyelination in the subcortical white matter and cerebellar white matter, and tauopathies. Selective vulnerabilities of different brain regions to heavy metal pollution in the AGR collected from the different regions of the country were evident. In conclusion, we propose that neuropathologies associated with redox dyshomeostasis because of environmental pollution may be localized and contextual, even in a heavily polluted environment. This novel study also highlights African giant rats as suitable epidemiological sentinels for use in ecotoxicological studies.

Vanadium improves memory and spatial learning and protects the pyramidal cells of the hippocampus in juvenile hydrocephalic mice.

Background: Hydrocephalus is a neurological condition known to cause learning and memory disabilities due to its damaging effect on the hippocampal neurons, especially pyramidal neurons. Vanadium at low doses has been observed to improve learning and memory abilities in neurological disorders but it is uncertain whether such protection will be provided in hydrocephalus. We investigated the morphology of hippocampal pyramidal neurons and neurobehavior in vanadium-treated and control juvenile hydrocephalic mice. Methods: Hydrocephalus was induced by intra-cisternal injection of sterile-kaolin into juvenile mice which were then allocated into 4 groups of 10 pups each, with one group serving as an untreated hydrocephalic control while others were treated with 0.15, 0.3 and 3 mg/kg i.p of vanadium compound respectively, starting 7 days post-induction for 28 days. Non-hydrocephalic sham controls (n = 10) were sham operated without any treatment. Mice were weighed before dosing and sacrifice. Y-maze, Morris Water Maze and Novel Object Recognition tests were carried out before the sacrifice, the brains harvested, and processed for Cresyl Violet and immunohistochemistry for neurons (NeuN) and astrocytes (GFAP). The pyramidal neurons of the CA1 and CA3 regions of the hippocampus were assessed qualitatively and quantitatively. Data were analyzed using GraphPad prism 8. Results: Escape latencies of vanadium-treated groups were significantly shorter (45.30 ± 26.30 s, 46.50 ± 26.35 s, 42.99 ± 18.44 s) than untreated group (62.06 ± 24.02 s) suggesting improvements in learning abilities. Time spent in the correct quadrant was significantly shorter in the untreated group (21.19 ± 4.15 s) compared to control (34.15 ± 9.44 s) and 3 mg/kg vanadium-treated group (34.35 ± 9.74 s). Recognition index and mean % alternation were lowest in untreated group (p = 0.0431, p=0.0158) suggesting memory impairments, with insignificant improvements in vanadium-treated groups. NeuN immuno-stained CA1 revealed loss of apical dendrites of the pyramidal cells in untreated hydrocephalus group relative to control and a gradual reversal attempt in the vanadium-treated groups. Astrocytic activation (GFAP stain) in the untreated hydrocephalus group were attenuated in the vanadium-treated groups under the GFAP stain. Pyknotic index in CA1 pyramidal layer of untreated (18.82 ± 2.59) and 0.15mg/kg vanadium-treated groups (18.14 ± 5.92) were significantly higher than control (11.11 ± 0.93; p = 0.0205, p = 0.0373) while there was no significant difference in CA3 pyknotic index across all groups. Conclusion: Our results suggest that vanadium has a dose-dependent protective effect on the pyramidal cells of the hippocampus and on memory and spatial learning functions in juvenile hydrocephalic mice.

Morphometric analysis of the spinal cord of the Sus scrofa (large white and landrace crossbreed).

The incidence of spinal cord (SC) injury in developed and undeveloped countries is alarming. The pig (Sus scrofa) has been recommended as a suitable research model for translational studies because of its morphophysiological similarities of organ systems with humans. There is a dearth of information on the SC anatomy of the large white and landrace crossbreed (LW-LC) pigs. We therefore aim to describe the gross morphology and morphometry of its SC. Twelve juvenile LW-LC pigs (six males and six females) were used. The skin and epaxial muscles were dissected to expose the vertebral column. The SC was carefully harvested by laminectomy, and 13 gross SC morphometric parameters were evaluated. Thirty-three spinal nerves were seen emanating from either side of the SC by means of dorsal and ventral spinal roots. The overall average of SC length and weight was 36.23 ± 1.01 cm and 16.60 ± 0.58 g, respectively. However, the mean SC length and weight were higher in females compared with males, with SC weight being statistically significant. A positive relationship between SC length and weight was significant for males (p = 0.0435) but not for females (p = 0.42). Likewise, the strength of the relationship between SC length and weight was significant in males (r = 0.82) but not significant in females (r = 0.41). Baseline data for the morphometric features of the spinal cord in the LW-LC pigs were generated, which will contribute to the knowledge of this species anatomy and useful information on regional anaesthesia that should further strengthen the drive in adopting the pig as a suitable research model for biomedical research.

Neurobehavioural and Histological Study of the Effects of Low-Dose and High-Dose Vanadium in Brain, Liver and Kidney of Mice.

Vanadium is a ubiquitous transition metal that has been generating contrasting research interest. Therapeutically, vanadium possess antidiabetic, antitumor, antiparasitic and even neuroprotective activities. On the flip side, vanadium has been reported to cause multisystemic toxicities with a strong predilection for the nervous system. Despite several reports on potential benefits of low-dose vanadium (LDV) and toxic effects of high-dose vanadium (HDV), there are no comparative studies done thus far. This study therefore explored the comparative effects of LDV and HDV exposure in mice during postnatal development. A total of nine (9) nursing mice were used in this study; with three nursing mice and their pups (n = 12 pups per group) randomly assigned to each of the three test groups. The nursing dam were given intraperitoneal (i.p) injection of vanadium at 0.15mg/kg and 3mg/kg for LDV and HDV respectively, and subseqently to the pups from postnatal day (PND) 15 till sacrifice on PND 90. We discovered that neurodevelopmental motor function test of mice-pups exposed to LDV here showed improved motor development, muscular strength and memory capacities whereas HDV led to motor function impairment, reduced muscular strength and memory capacities.  LDV-exposed mice showed mild histological lesions in cerebral cortex whereas high-dose showed distinct histological lesions in different parts of the brain ranging from cerebellar Purkinje neuronal pathology (central chromatolysis), pyramidal neuronal loss in CA1 region, architectural distortion as well as fewer neurons in olfactory bulb. We saw mild lesions with LDV in both liver and kidney, however, with HDV exposure, there was diffuse hepatocellular vacuolar degeneration and congestion of blood vessels in liver, shrinkage of renal glomerulus and degenerated epithelial cells of kidney. Conclusively, beneficial effect of vanadium is proven as it facilitated body weight gain which translate in organ weight at low-dose, while high-dose caused decreased neurobehaviour and histological lesions.

Probing Caffeine Administration as a Medical Management for Hydrocephalus: An Experimental Study.

BACKGROUND: Hydrocephalus is currently managed by cerebrospinal fluid diversion from the cerebral ventricles to other body sites, but this is complicated by obstruction and infection in young infants, thus adding to morbidity and mortality. Studies have reported caffeine to be a pleiotropic neuroprotective drug in the developing brain due to its antioxidant, anti-inflammatory, and antiapoptotic properties, with improved white matter microstructural development. In this study, we investigate the use of caffeine administration as a possible means of pharmacological management for hydrocephalus. METHODS: A total of 76 three-day-old mice pups from 10 dams were divided into four groups: hydrocephalus was induced in the pups in two groups by intracisternal injection of kaolin suspension, and their dams were given either caffeine (50 mg/kg by gavage) or water daily for 21 days; the dams in the other 2 (non-hydrocephalic) groups similarly had either caffeine or water; the pups received caffeine administered via lactation. Developmental neurobehavioral tests were performed until day 21, when the pups were sacrificed. Their brains were removed and processed for Cresyl and Golgi staining; both quantitative and qualitative analyses were then carried out. RESULTS: Improved developmental motor activities and reflexes were observed in the hydrocephalus + caffeine-treated pups. Caffeine administration was associated with reduced cell death and increased dendritic arborization of the neurons in the sensorimotor cortex and striatum of hydrocephalic mice pups. CONCLUSION: Caffeine administration appears to have promise as an adjunct in hydrocephalus management, and its use needs to be further explored.

Neuroecotoxicology: Effects of environmental heavy metal exposure on the brain of African giant rats and the contribution of vanadium to the neuropathology.

Increased exploitation of minerals has led to pollution of confined environments as documented in Nigeria Niger Delta. Information on the effects on brain of such exposure is limited. Due to its exploratory activities, the African giant rat (Cricetomys gambianus) (AGR) provides a unique model for neuroecotoxicological research to determine levels of animal and human exposure to different pollutants. This study aims to unravel neuropathological features of AGR sampled from three agro-ecological zones of Nigeria. Fifteen AGR were sampled according to previously determined data on heavy metal exposure: high vanadium, high lead, and low metals. Eighteen AGR were collected from low metal zone and divided into two groups. Control group received vehicle while SMV exposed group received 3 mg/kg sodium metavanadate (SMV) intraperitoneally for 14days. Brain immunohistochemical analyses were conducted, and ultrastructural changes were studied in experimentally exposed group. Results showed significant loss of tyrosin hydroxylase, parvalbumin, orexin-A and melanin concentration hormone containing neuronal populations in brains obtained from high vanadium and high lead zones and in experimentally intoxicated SMV groups. Similarly, significant decrease numbers of dendritic arborations; extracellular matrix density, perineuronal nets; astrocytes and microglia activations are documented in same groups. Ultrastructural studies revealed mass denudation, cilia loss, disintegration of ependymal layer and intense destructions of myelin sheaths in SMV exposed group. These are the first "neuroecotoxicological" findings in distinct neuronal cells. The implications of these findings are highly relevant for human population living in these areas, not only in Nigeria but also in similarly polluted areas elsewhere in the world.

Neurotoxicity and Behavioral Alterations Following Subchronic Administration of Aqueous Extract of Erythrophleum Ivorense Stem Bark in Mice.

INTRODUCTION: Erythrophleum Ivorense (EI) is a tree found across tropical Africa. The bark of EI is widely used as hunting poisons for animals and ordeal poison in humans. Eating this plant causes paralysis, respiratory distress, and amnesia. In folklore, these behavioral changes have been attributed to guilt in victims; nonetheless, no scientific evidence supports this claim. Thus, the mechanism of neurotoxicity and behavioral alteration of this plant should be investigated. METHODS: A total of 48 BALB/c male mice were randomly divided into four groups. The three experimental groups were administered an aqueous extract of EI in a single daily dose of 5, 10, and 15 mg/kg bodyweight for 28 days, while the control group received distilled water. Afterward, the motor coordination, learning, memory, and grip strength of the mice were accessed with wire grip, Morris water maze, and inverted wire mesh grid grip tests. Histological staining of brain sections was also carried out. RESULTS: At all tested doses, the aqueous extract of EI caused a significant reduction in hanging latency, significantly increased escape latency, and decreased duration of the target platform in the Morris water maze test compared to control. Reduced grip strength was also observed in the test groups compared to the control. Histology revealed dysmorphic and disoriented Purkinje cells and loss of this cell layer of the cerebellum. CONCLUSION: Erythrophleum ivorense administration altered motor coordination, learning and memory, and grip strength in mice dose-dependently. It also caused disruption of granule cells layer, loss of Purkinje cells, and altered cerebellar anatomy leading to motor deficits in mice.

Chronic caffeine ingestion improves memory and learning and increases neuronal population and dendritic length in the hippocampus of adult mice.

Caffeine is the most widely consumed psychoactive drug in the world, ingested as natural components of chocolate, coffee and tea and as added components to soda and energy drinks. Here we assessed behavioural changes caused by chronic caffeine administration as well as morphological changes within specific regions of the adult mice brain: the hippocampus and amygdala. Twenty-four adult male albino mice were randomly divided into three groups. Caffeine was administered daily by gavage for 8 weeks at a dosage of 20 mg/kg for low dose (LD) group and 60 mg/kg for high dose (HD) group while the third group served as control (CNT). After the period of administration, neurobehavioural tasks were carried out; Morris water maze for learning and memory open field test and elevated plus maze test for anxiety. The mice were sacrificed; their brain tissues were harvested and processed for H&E, Cresyl violet and Golgi staining, and assessed qualitatively and quantitatively. Quantitative data from the neurobehavioural tests and neuronal cell counts were expressed as means ± standard errors of means and compared across the groups using analysis of variance (ANOVA). Significance was set at p< 0.05. Mice in the high dose group learnt faster and had significantly increased number of platform crossings in the Morris water maze test. There was, however, a slightly increased level of anxiety in the caffeine-treated mice, compared to controls. Histo-morphometric analysis revealed significantly increased number of pyramidal neurons in the hippocampus in the low dose group, but a decreased neuronal count in the amydala of the low dose and high dose groups compared to controls. The pyramidal neurons in the hippocampus of the caffeine-treated mice had increased apical dendritic length compared to the controls. Our findings strengthen the available data suggesting that prolonged caffeine intake improves cognition, and this process could be mediated by promoting the growth of dendrites and increased number of neurons. However, this is coupled with an increased tendency to be anxiogenic.

Essential Metals in the Brain and the Application of Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry for their Detection.

Metals are natural component of the ecosystem present throughout the layers of atmosphere; their abundant expression in the brain indicates their importance in the central nervous system (CNS). Within the brain tissue, their distribution is highly compartmentalized, the pattern of which is determined by their primary roles. Bio-imaging of the brain to reveal spatial distribution of metals within specific regions has provided a unique understanding of brain biochemistry and architecture, linking both the structures and the functions through several metal mediated activities. Bioavailability of essential trace metal is needed for normal brain function. However, disrupted metal homeostasis can influence several biochemical pathways in different fields of metabolism and cause characteristic neurological disorders with a typical disease process usually linked with aberrant metal accumulations. In this review we give a brief overview of roles of key essential metals (Iron, Copper and Zinc) including their molecular mechanisms and bio-distribution in the brain as well as their possible involvement in the pathogenesis of related neurodegenerative diseases. In addition, we also reviewed recent applications of Laser Ablation Inductively Couple Plasma Mass Spectrophotometry (LA-ICP-MS) in the detection of both toxic and essential metal dyshomeostasis in neuroscience research and other related brain diseases.

Kolaviron protects rats from cognitive decline induced by Lipopolysaccharide in Wistar rat.

  Kolaviron is a mixture of bi-flavonoids from seed Garcinia kola seed, and has been previously shown to exhibit Nrf2 antioxidant-mediated inhibition of neuroinflammation in LPS-activated BV2 microglia. In this study, we investigated neuroprotective effects of kolaviron in LPS-induced memory impairment in rats. Wistar rats (225-250) g was used for this study. Memory impairment was induced with the systematic administration of 250 µg/mg lipopolysaccharide (LPS). The effect of kolaviron on the cognition and learning processes were assessed using the behavioral responses in the Morris water maze model. Effects of LPS injections on the physiological activities were assessed by biochemical assays before and after treatment. Peripheral administration of LPS showed reduction in the cognitive and locomotor process. It also led to reductions in the core body temperature, superoxide dismutase (SOD), and catalase levels, with an increase in Membrane lipid-peroxidation (MDA), intracellular glutathione (GSH) and nitric oxide (NO2). These pro-inflammatory mediators produced in response to LPS are hypothesized to affect cognition, and kolaviron was able to ameliorate the effect by significantly improving the cognitive and learning processes, revealed in the reduction of escape latency and path-length during the probe trial and increase in time spent within the quadrant during retrieval using Morris water maze. Similarly, LPS at 250 µg/kg induced a hypothermic effect in the treated animals. Kolaviron significantly was able to ameliorate the level of SOD and CAT by causing a significant increase while it caused a significant reduction in the level of NO2, GSH, and MDA. Kolaviron has considerable anti-inflammatory potentials, reducing lipopolysaccharide activation of macrophages. The memory-enhancing activity of kolaviron was comparable to Sulindac sulfide (a non-steroidal anti-inflammatory drug).

Neurobehavioural changes and morphological study of cerebellar purkinje cells in kaolin induced hydrocephalus.

Cerebellar abnormalities are commonly associated with hydrocephalus. However, the effect of hydrocephalus on the otherwise normal cerebellum has been largely neglected. This study assesses the morphological changes in the Purkinje cells in relation to cerebellar dysfunction observed in juvenile hydrocephalic rats. Fifty-five three-week old albino Wistar rats were used, hydrocephalus was induced by intracisternal injection of kaolin (n = 35) and others served as controls (n = 20). Body weight measurements, hanging wire, negative geotaxis, and open field tests were carried out at the onset and then weekly for 4 weeks, rats were killed, and their cerebella processed for Hematoxylin and Eosin, Cresyl violet and Golgi staining. Qualitative and quantitative studies were carried out; quantitative data were analyzed using two-way ANOVA and independent T tests at p < 0.05. Hydrocephalic rats weighed less than controls (p = 0.0247) but their cerebellar weights were comparable. The hydrocephalic rats had a consistently shorter latency to fall in the hanging wire test (F(4,112) = 18.63; p < 0.0001), longer latency to turn in the negative geotaxis test (F(4,112) = 22.2; p < 0.0001), and decreased horizontal (F(4,112) = 4.172, p = 0.0035) and vertical movements (F(4,112) = 4.397; p = 0.0024) in the open field test than controls throughout the 4 weeks post-induction. Cellular compression in the granular layer, swelling of Purkinje cells with vacuolations, reduced dendritic arborization and increased number of pyknotic Purkinje cells were observed in hydrocephalic rats. Hydrocephalus caused functional and morphological changes in the cerebellar cortex. Purkinje cell loss, a major pathological feature of hydrocephalus, may be responsible for some of the motor deficits observed in this condition.

The Pathopharmacological Interplay between Vanadium and Iron in Parkinson's Disease Models.

Parkinson's disease (PD) pathology is characterised by distinct types of cellular defects, notably associated with oxidative damage and mitochondria dysfunction, leading to the selective loss of dopaminergic neurons in the brain's substantia nigra pars compacta (SNpc). Exposure to some environmental toxicants and heavy metals has been associated with PD pathogenesis. Raised iron levels have also been consistently observed in the nigrostriatal pathway of PD cases. This study explored, for the first time, the effects of an exogenous environmental heavy metal (vanadium) and its interaction with iron, focusing on the subtoxic effects of these metals on PD-like oxidative stress phenotypes in Catecholaminergic a-differentiated (CAD) cells and PTEN-induced kinase 1 (PINK-1)B9Drosophila melanogaster models of PD. We found that undifferentiated CAD cells were more susceptible to vanadium exposure than differentiated cells, and this susceptibility was modulated by iron. In PINK-1 flies, the exposure to chronic low doses of vanadium exacerbated the existing motor deficits, reduced survival, and increased the production of reactive oxygen species (ROS). Both Aloysia citrodora Paláu, a natural iron chelator, and Deferoxamine Mesylate (DFO), a synthetic iron chelator, significantly protected against the PD-like phenotypes in both models. These results favour the case for iron-chelation therapy as a viable option for the symptomatic treatment of PD.

Neuroinflammatory Response in Chronic Hydrocephalus in Juvenile Rats.

Hydrocephalus is especially prevalent in countries with limited resources, where its treatment is still a challenge. However, long-term neuropathological changes in untreated hydrocephalus remain largely unexplored. The present study looks at cortical parenchyma and neuroinflammation in acquired, chronic hydrocephalus. Intracisternal kaolin injections were performed in 3-week-old rats, followed by -1, 4- and 8-week survival; matched control rats received saline injections. Ventriculomegaly has been previously reported to stabilize by the third week in this model. Single and triple immunocytochemical approaches were used to highlight neurones, astrocytes, microglia, and the pro-inflammatory cytokine interleukin (IL)-1ß in the parietal cortex, utilizing cell counts and densitometry. Microglial protein ionized calcium binding adaptor molecule 1 (Iba1) and IL-1ß expressions were monitored with Western blotting in the parietal cortex and hippocampus. In the parietal cortex, which showed progressive disruption of cytoarchitecture, neuronal density was significantly increased at 8weeks post-induction but not at earlier time points, indicating on-going cortical damage in chronic hydrocephalus. Astrocyte and microglia hypertrophy, and Iba1 expression indicated glial cell activation which peaked at 4weeks. IL-1ß expression also peaked at 4weeks and was then down-regulated. Overall the findings indicate that neuroinflammatory features build up in the first month after hydrocephalus induction implicating marked IL-1ß upregulation. The data also show that astrocytes are the main source of IL-1ß in this disorder.

Trends in vanadium neurotoxicity.

Vanadium, atomic number 23, is a transition metal widely distributed in nature. It is a major contaminant of fossil fuels and is widely used in industry as catalysts, in welding, and making steel alloys. Over the years, vanadium compounds have been generating interests due to their use as therapeutic agents in the control of diabetes, tuberculosis, and some neoplasms. However, the toxicity of vanadium compounds is well documented in literature with occupational exposure of workers in vanadium allied industries, environmental pollution from combustion of fossil fuels and industrial exhausts receiving concerns as major sources of toxicity and a likely predisposing factor in the aetiopathogenesis of neurodegenerative diseases. A lot has been done to understand the neurotoxic effects of vanadium, its mechanisms of action and possible antidotes. Sequel to our review of the subject in 2011, this present review is to detail the recent insights gained in vanadium neurotoxicity.

Brain Metal Distribution and Neuro-Inflammatory Profiles after Chronic Vanadium Administration and Withdrawal in Mice.

Vanadium is a potentially toxic environmental pollutant and induces oxidative damage in biological systems including the central nervous system (CNS). Its deposition in brain tissue may be involved in the pathogenesis of certain neurological disorders which after prolonged exposure can culminate into more severe pathology. Most studies on vanadium neurotoxicity have been done after acute exposure but in reality some populations are exposed for a lifetime. This work was designed to ascertain neurodegenerative consequences of chronic vanadium administration and to investigate the progressive changes in the brain after withdrawal from vanadium treatment. A total of 85 male BALB/c mice were used for the experiment and divided into three major groups of vanadium treated (intraperitoneally (i.p.) injected with 3 mg/kg body weight of sodium metavanadate and sacrificed every 3 months till 18 months); matched controls; and animals that were exposed to vanadium for 3 months and thereafter the metal was withdrawn. Brain tissues were obtained after animal sacrifice. Sagittal cut sections of paraffin embedded tissue (5 µm) were analyzed by the Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) to show the absorption and distribution of vanadium metal. Also, Haematoxylin and Eosin (H&E) staining of brain sections, and immunohistochemistry for Microglia (Iba-1), Astrocytes (GFAP), Neurons (Neu-N) and Neu-N + 4',6-diamidine-2'-pheynylindole dihydrochloride (Dapi) Immunofluorescent labeling were observed for morphological and morphometric parameters. The LA-ICP-MS results showed progressive increase in vanadium uptake with time in different brain regions with prediction for regions like the olfactory bulb, brain stem and cerebellum. The withdrawal brains still show presence of vanadium metal in the brain slightly more than the controls. There were morphological alterations (of the layering profile, nuclear shrinkage) in the prefrontal cortex, cellular degeneration (loss of dendritic arborization) and cell death in the Hippocampal CA1 pyramidal cells and Purkinje cells of the cerebellum, including astrocytic and microglial activation in vanadium exposed brains which were all attenuated in the withdrawal group. With exposure into old age, the evident neuropathology was microgliosis, while progressive astrogliosis became more attenuated. We have shown that chronic administration of vanadium over a lifetime in mice resulted in metal accumulation which showed regional variabilities with time. The metal profile and pathological effects were not completely eliminated from the brain even after a long time withdrawal from vanadium metal.

Developing a competency-based medical education curriculum for the core basic medical sciences in an African Medical School.

The College of Medicine of the University of Ibadan recently revised its MBBS and BDS curricula to a competency-based medical education method of instruction. This paper reports the process of revising the methods of instruction and assessment in the core basic medical sciences directed at producing medical and dental graduates with a sound knowledge of the subjects sufficient for medical and dental practice and for future postgraduate efforts in the field or related disciplines. The health needs of the community and views of stakeholders in the Ibadan medical and dental schools were determined, and the "old" curriculum was reviewed. This process was directed at identifying the strengths and weaknesses of the old curricula and the newer competences required for modern-day medical/dental practice. The admission criteria and processes and the learning methods of the students were also studied. At the end of the review, an integrated, system-based, community-oriented, person-centered, and competency-driven curriculum was produced and approved for implementation. Four sets of students have been admitted into the curriculum. There have been challenges to the implementation process, but these have been overcome by continuous faculty development and reorientation programs for the nonteaching staff and students. Two sets of students have crossed over to the clinical school, and the consensus among the clinical teachers is that their knowledge and application of the basic medical sciences are satisfactory. The Ibadan medical and dental schools are implementing their competency-based medical education curricula successfully. The modifications to the teaching and assessment of the core basic medical science subjects have resulted in improved learning and performance at the final examinations.

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.