Reimagining the future of African brain health: Perspectives for basic research on the pathogenesis of cryptococcal meningitis.

Cryptococcal meningitis is a fatal opportunistic infection of the brain and a leading cause of neurological damage and death in immunocompromised individuals. This neglected fungal disease of the brain is a huge burden on the health systems of developing countries, especially in Sub-Saharan Africa, where up to 25% of people living with HIV/AIDS succumb to it. Cryptococcal fungal cells have a predilection for the brain and they are capable of traversing the blood brain barrier and invade the brain where they cause infection, inflammation and a disruption of normal brain function. A robust host neuroimmune response is critical for pathogen clearance and survival, and a good understanding of the mechanisms underlying its development in the host is critical for the development of effective treatments. However, past basic research studies have been focussed on the characteristics of the fungus and its effect on the peripheral immune system; with little attention paid to how it interacts with brain immune cells. This mini review briefly discusses the paucity of basic research data on the neuroimmune response to cryptococcal infection, raises pertinent questions on how the brain cells respond to the fungal infection, and thereafter discusses models, techniques and advanced technologies that could be useful for carrying out high-throughput research on the pathogenesis of cryptococcal meningitis.

Brewer's yeast is a potent inducer of fever, sickness behavior and inflammation within the brain.

Brewer's yeast, derived from the yeast species Saccharomyces cerevisiae (S. cerevisiae), is commonly used for inducing pyrexia in pharmacological studies screening antipyretics in rats. Despite its widespread use, the peripheral and central inflammatory response associated with Brewer's yeast-induced fever and sickness behavior in rats has not been investigated. Thus, we injected male Sprague-Dawley rats (150-200 g) subcutaneously with a high (4 g/kg, n = 9), medium (2 g/kg, n = 5) or low (0.4 g/kg, n = 6) dose of Brewer's yeast solution or saline (0.9%, n = 6) and measured core body temperature, cage activity, food intake and body mass for six days after injection. Blood and brain samples were collected at 2, 8, 18 and 72 h after injection; n = 5-7 per time point. Brewer's yeast administration dose-dependently induced fever, lethargy, anorexia and body mass stunting that was accompanied by increased blood plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α and activation of inflammatory transcription factors (nuclear factor (NF) for interleukin-6, signal transducer and activator of transcription (STAT)-3, and NF-κB)) in the hypothalamus and circumventricular organs. The increased activation of transcription factors following Brewer's yeast administration was accompanied by increased hypothalamic mRNA expression of TNF-α, IL-1ß and IL-6 and rate-limiting enzymes for prostaglandin synthesis. Our results show that subcutaneous administration of S. cerevisae induces prolonged fever, anorexia and lethargy that is accompanied by a pronounced increase in the synthesis of pro-inflammatory cytokines, key prostaglandin synthesizing enzymes and transcription factors, in the periphery and brain.

Effect of dietary Ximenia caffra kernel meal on blood and liver metabolic substrate content and the general clinical biochemistry of Sprague Dawley rats.

We investigated (at the University of the Witwatersrand: GPS coordinates 26°10' 52.96″S; 28°2' 33.61″E) the effects of substituting soya bean meal (SBM) with Ximenia caffra kernel meal (XCKM) as a dietary protein source on blood and liver metabolic substrates content, serum markers of liver and kidney function and the general clinical biochemistry of Sprague Dawley (SD) rats. Five diets with similar energy and protein content were formulated (D1-D5) where XCKM replaced SBM on a crude protein basis at 0, 25, 50, 75 and 100%. Forty weanling male SD rats were randomly assigned to diets D1-D5, fed for 37 days and weighed twice weekly. The rats were then fasted overnight, and fasting blood glucose and triglyceride concentrations were determined from tail-vein-drawn blood. Immediately thereafter, the rats were euthanised and blood was collected via cardiac puncture. Serum was used to assay for markers of the general health profile. Livers were removed and weighed, and samples were used to determine lipid and glycogen content. Rats fed D4 (75% substitution level) had significantly lower (p < 0.05) blood triglyceride content compared with rats fed D2 (25% level of substitution). The substitution of SBM with XCKM did not affect (p > 0.05) fasting blood glucose and cholesterol concentrations, liver glycogen and lipid content. Additionally, it had no effect (p > 0.05) on serum activity/concentration of surrogate markers of liver (alanine aminotransferase and alkaline phosphatase activity and urea, total bilirubin, globulin and albumin concentrations) and kidney (phosphorus, calcium and creatinine concentrations) function and the general clinical biochemistry of the rats. Defatted XCKM could substitute SBM in rat diets without compromising blood glucose and cholesterol homeostasis, liver and kidney function and the general clinical biochemistry of growing male Sprague Dawley rats.

Effects of Ficus thonningii extracts on the gastrointestinal tract and clinical biochemistry of suckling rats.

BACKGROUND: Ficus thonningii is commonly used in traditional medicine across the African continent. We investigated the effects of crude Ficus thonningii extracts on growth, morphology and morphometry of the abdominal viscera and clinical biochemistry of neonatal rats. MATERIALS AND METHODS: Forty, 6-day old Sprague Dawley rat pups were orally gavaged once daily with either low (50 mg.kg(-1) b.w) or high (500 mg.kg(-1) b.w) doses of aqueous or methanolic F. thonningii leaf extracts while the control received distilled water. After 7 days of treatment, the pups were euthanased and gross morphometric measurements of the abdominal visceral organs were recorded. Samples of the liver, caecum and proximal small intestine were processed for histology. Plasma biochemical parameters were analysed colorimetrically. RESULTS: High methanolic doses of F. thonningii extracts exhibited trophic effects on the stomach while both aqueous and methanolic extracts had trophic effects on the ceacal mucosa of rats. No significant growth-promoting effects were observed in other visceral organs. Histological analysis revealed no mucosal damage or necrosis. Clinical biochemistry parameters were not abnormally altered. There was a significant decrease (p<0.05, ANOVA) in the plasma concentration of non-fasting glucose in the high methanolic group but triglycerides and cholesterol were unaltered. CONCLUSION: The findings suggest that at low doses, F. thonningii extracts can be safely used without the risk of any disruption in the structural integrity of the neonatal rat GIT and function of the liver and kidneys.

The progressive effects of a high-fat diet on erythrocyte osmotic fragility, growth performance and serum triglyceride and cholesterol levels in Guinea fowl (Numida meleagris) and Muscovy duck (Cairina moschata).

To investigate the progressive effects of a high-fat diet on erythrocyte osmotic fragility, growth performance and serum lipid concentrations in Guinea fowl and Muscovy ducks, 36 Guinea fowl and 36 Muscovy ducks were divided into two groups, for each species, and fed either a standard (STD = commercial poultry feed) or high-fat diet (HFD = commercial poultry feed with 20% palm oil and 2% lard) for up to 12 weeks. After 4, 8 and 12 weeks on the diets, six birds from each group were euthanized and blood samples collected. Osmotic fragility was assessed by measuring the haemoglobin released by erythrocytes placed in serially diluted solutions of phosphate-buffered saline, spectrophotometrically. Serum triglyceride and cholesterol concentrations were also determined. Fragiligrams from erythrocytes from both species of birds on the HFD were not different to those on the STD. However, Muscovy duck erythrocytes were more resistant to haemolysis compared with Guinea fowl erythrocytes. Final body mass and serum triglyceride levels were not significantly different (p > 0.05, anova) between the birds in the HFD and STD groups, for both species of birds. In contrast, serum cholesterol levels were significantly higher in birds on the HFD compared with those on the STD, after 4, 8 and 12 weeks of feeding, for both species of birds. Feeding Guinea fowl and Muscovy ducks a high-fat diet for up to 12 weeks resulted in hypercholesterolaemia but had no effect on final body mass, erythrocyte osmotic fragility or serum triglyceride concentrations in either bird species.