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.

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.

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.

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.

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.

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.

The relationship between ventricular dilatation, neuropathological and neurobehavioural changes in hydrocephalic rats.

BACKGROUND: The motor and cognitive deficits observed in hydrocephalus are thought to be due to axonal damage within the periventricular white matter. This study was carried out to investigate the relationship between ventricular size, cellular changes in brain, and neurobehavioural deficits in rats with experimental hydrocephalus. METHODS: Hydrocephalus was induced in three-week old rats by intracisternal injection of kaolin. Behavioural and motor function were tested four weeks after hydrocephalus induction and correlated to ventricular enlargement which was classified into mild, moderate or severe. Gross brain morphology, routine histology and immunohistochemistry for oligodendrocytes (CNPase), microglia (Iba-1) and astrocytes (GFAP) were performed to assess the cellular changes. RESULTS: Decreases in open field activity and forelimb grip strength in hydrocephalus correlated with the degree of ventriculomegaly. Learning in Morris water maze was significantly impaired in hydrocephalic rats. Gradual stretching of the ependymal layer, thinning of the corpus callosum, extracellular oedema and reduced cortical thickness were observed as the degree of ventriculomegaly increased. A gradual loss of oligodendrocytes in the corpus callosum and cerebral cortex was most marked in the severely-hydrocephalic brains, whereas the widespread astrogliosis especially in the subependymal layer was most marked in the brains with mild hydrocephalus. Retraction of microglial processes and increase in Iba-1 immunoreactivity in the white matter was associated ventriculomegaly. CONCLUSIONS: In hydrocephalic rats, oligodendrocyte loss, microglia activation, astrogliosis in cortical areas and thinning of the corpus callosum were associated with ventriculomegaly. The degree of ventriculomegaly correlated with motor and cognitive deficits.