Influence of the lateral ventricles and irregular skull base on brain kinematics due to sagittal plane head rotation

Two-dimensional physical models of the human head were used to investigate how the lateral ventricles and irregular skull base influence kinematics in the medial brain during sagittal angular head dynamics. Silicone gel simulated the brain and was separatedfrom the surrounding skull vessel by paraffin that provided a slip interface between the gel and vessel. A humanlike skull base model (HSB) included a surrogate skull base mimicking the irregular geometry of the human. An HSBV model added an elliptical inclusion filled with liquid paraffin simulating the lateral ventricles to the HSB model. A simplified skull base model (SSBV) included ventricle substitute but approximated the anterior and middle cranial fossae by a flat and slightly angled surface. The models were exposed to 7600 rad/s2 peak angular acceleration with 6 ms pulse duration and 5 deg forced rotation. After 90 deg free rotation, the models were decelerated during 30 ms. Rigid body displacement, shear strain and principal strains were determined from high-speed video recorded trajectories of grid markers in the surrogate brains. Peak values of inferior brain surface displacement and strains were up to 10.9X (times) and 3.3X higher in SSBV than in HSBV. Peak strain was up to 2.7X higher in HSB than in HSBV. The results indicate that the irregular skull base protects nerves and vessels passing through the cranial floor by reducing brain displacement and that the intraventricular cerebrospinal fluid relieves strain in regions inferior and superior to the ventricles. The ventricles and irregular skull base are necessary in modeling head impact and understanding brain injury mechanisms.     

The impact of transgenic plants on natural enemies: a critical review of laboratory studies

We reviewed laboratory tests which studied the impact of genetically modified plants on arthropod natural enemies. A total of 18 species of predators and 14 species of parasitoids have been tested, most in only a few experiments. Certain groups (braconid wasps) or species (the green lacewing, Chrysoperla carnea) have attracted much effort, while representatives of others, including whole orders (e.g., Diptera), have never had a species tested. We conclude that laboratory tests are not the ‘worst case’ scenarios intended by the experimental designs, and are not often ecologically realistic: they typically provided ad libitum feeding, no prey choice, single prey type, no combination of stress factors and usually uniform temperatures. None of these are representative of field conditions, yet most could be easily mimicked in more complex laboratory tests. In most cases (94.6%), the studies were unable to indicate the level of power required to detect any impact. Small sample size and large variability are factors that mask all but very large differences in potential effects. For predators, 126 parameters were quantified, most commonly including survival/mortality (37 cases), development time (22), and body mass/size (20). For parasitoids, 128 parameters were quantified, the majority involving lectins or proteinase inhibitors. Most frequent measurements were: fecundity (23 experiments), adult longevity, extent of parasitism (17 each), body size, mortality, and larval development time. An aggregative scoring (summarising all quantified parameters) indicated that the laboratory tests quantified a remarkable number of cases (30% for predators, 39.8% for parasitoids), where the impacts of the genetically modified plant were significantly negative. These involve various parameters, organisms, test methods, and significance levels, but collectively they indicate that the use of genetically modified crops may result in negative effects on the natural enemies of crop pests.     

Lycium barbarum extracts protect the brain from blood-brain barrier disruption and cerebral edema in experimental stroke

Background and Purpose

Ischemic stroke is a destructive cerebrovascular disease and a leading cause of death. Yet, no ideal neuroprotective agents are available, leaving prevention an attractive alternative. The extracts from the fruits of Lycium barbarum (LBP), a Chinese anti-aging medicine and food supplement, showed neuroprotective function in the retina when given prophylactically. We aim to evaluate the protective effects of LBP pre-treatment in an experimental stroke model.

Methods

C57BL/6N male mice were first fed with either vehicle (PBS) or LBP (1 or 10 mg/kg) daily for 7 days. Mice were then subjected to 2-hour transient middle cerebral artery occlusion (MCAO) by the intraluminal method followed by 22-hour reperfusion upon filament removal. Mice were evaluated for neurological deficits just before sacrifice. Brains were harvested for infarct size estimation, water content measurement, immunohistochemical analysis, and Western blot experiments. Evans blue (EB) extravasation was determined to assess blood-brain barrier (BBB) disruption after MCAO.

Results

LBP pre-treatment significantly improved neurological deficits as well as decreased infarct size, hemispheric swelling, and water content. Fewer apoptotic cells were identified in LBP-treated brains by TUNEL assay. Reduced EB extravasation, fewer IgG-leaky vessels, and up-regulation of occludin expression were also observed in LBP-treated brains. Moreover, immunoreactivity for aquaporin-4 and glial fibrillary acidic protein were significantly decreased in LBP-treated brains.

Conclusions

Seven-day oral LBP pre-treatment effectively improved neurological deficits, decreased infarct size and cerebral edema as well as protected the brain from BBB disruption, aquaporin-4 up-regulation, and glial activation. The present study suggests that LBP may be used as a prophylactic neuroprotectant in patients at high risk for ischemic stroke.     

Studies on the glycoprotein modification in erythrocyte membrane during experimental cerebral malaria

Plasmodium berghei ANKA (Pb ANKA) is a lethal strain of malaria that causes experimental cerebral malaria (ECM) in rodent models. Pathology of the disease is associated with the sequestration of the infected rbc (irbc) in the micro vessels of brain. In the present study, we analyzed the nature of the glycoprotein modification occurring in irbc membrane during erythrocytic stages of Pb ANKA infection. Titration of naturally occurring glycoproteins with concanavalin A (Con A) and wheat germ agglutinin (WGA) lectins revealed an enhanced lectin binding ability for the irbc membrane preparations. Partial characterization of the Con A specific determinants (alpha-d-methyl mannoside specificity) by lectin affinity chromatography followed by 2D electrophoresis and WGA specific determinants (sialic acid specificity) by Western analysis revealed the association of novel lectin specific determinants in irbc membrane. To correlate the biochemical changes with the morphological changes, SEM of irbc, and TEM of sequestered irbc were performed. These ultra structural studies revealed variable and irregular surface protrusions and deep surface indentations on irbc. These observations implicate that altered glycoprotein profiles may lead to cytoarchitectural changes in irbc membrane and such changes may be essential to establish contact with the host endothelial cells. These observations may be central to the microvascular sequestration and pathology of ECM.     

Exogenous GSH protection during hypoxia-reoxygenation of the isolated rat heart: impact of hypoxia duration

The objective of this study was to determine the interaction between duration of myocardial hypoxia and presence of exogenous glutathione (GSH) on functional recovery upon subsequent reoxygenation. Isolated perfused rat hearts were subjected to 20, 30, 40, or 50 min hypoxia (HYP), which resulted in a progressive decline in the amount of contractile recovery (% of normoxic rate-pressure product (RPP) and developed pressure) during 30 min reoxygenation. Supplementation with 5 mM GSH throughout normoxia, hypoxia, and reoxygenation significantly improved contractile recovery during reoxygenation after 20 and 30 min hypoxia (p < 0.05), but had no effect after longer durations of hypoxia when contractile recovery was typically below 40% of RPP and significant areas of no-reflow were observed. ECG analysis revealed that GSH shifted the bell-shaped curve for reperfusion ventricular fibrillation to the right resulting in attenuated fibrillation after 20 and 30 min hypoxia then increased incidences after 40 min when Control hearts were slow to resume electrical activity. ECG conduction velocity was well preserved in all hearts after 20 and 30 min hypoxia, but GSH administration significantly attenuated the decline that occurred with longer durations. GSH supplementation did not attenuate the 35% decline in intracellular thiols during 30 min of hypoxia. When 5 mM GSH was added only during 40 min of hypoxia, RPP recovery after reoxygenation was improved compared to unsupplemented Controls (73% vs. 55% of pre-hypoxia value, p < 0.05). Administration of GSH only during reoxygenation following 40 min of hypoxia did not alter RPP recovery compared to Control hearts. We conclude that cardioprotection by exogenous GSH is dependent on the duration of hypoxia and the functional parameter being evaluated. It is not due to an enhancement of intracellular GSH suggesting that exogenous GSH acts extracellularly to protect sarcolemmal proteins against thiol oxidation during the phase of hypoxia when oxidative stress is a major contributor to cardiac dysfunction. Furthermore, if enough damage accrues during oxygen deprivation, supplementing with GSH during reoxygenation will not impact recovery.     

Mechanisms of methylmercury-induced neurotoxicity: evidence from experimental studies

Neurological disorders are common, costly, and can cause enduring disability. Although mostly unknown, a few environmental toxicants are recognized causes of neurological disorders and subclinical brain dysfunction. One of the best known neurotoxins is methylmercury (MeHg), a ubiquitous environmental toxicant that leads to long-lasting neurological and developmental deficits in animals and humans. In the aquatic environment, MeHg is accumulated in fish, which represent a major source of human exposure. Although several episodes of MeHg poisoning have contributed to the understanding of the clinical symptoms and histological changes elicited by this neurotoxicant in humans, experimental studies have been pivotal in elucidating the molecular mechanisms that mediate MeHg-induced neurotoxicity. The objective of this mini-review is to summarize data from experimental studies on molecular mechanisms of MeHg-induced neurotoxicity. While the full picture has yet to be unmasked, in vitro approaches based on cultured cells, isolated mitochondria and tissue slices, as well as in vivo studies based mainly on the use of rodents, point to impairment in intracellular calcium homeostasis, alteration of glutamate homeostasis and oxidative stress as important events in MeHg-induced neurotoxicity. The potential relationship among these events is discussed, with particular emphasis on the neurotoxic cycle triggered by MeHg-induced excitotoxicity and oxidative stress. The particular sensitivity of the developing brain to MeHg toxicity, the critical role of selenoproteins and the potential protective role of selenocompounds are also discussed. These concepts provide the biochemical bases to the understanding of MeHg neurotoxicity, contributing to the discovery of endogenous and exogenous molecules that counteract such toxicity and provide efficacious means for ablating this vicious cycle.     

The impact of malnutrition on human lactation: observations from community studies

There is very little scope for the direct examination of relationships between nutrient intake and lactational performance in women. Experimental investigations are limited to the effects of dietary supplementation in pregnancy and/or lactation. To obtain comparisons between normal and undernourished women, studies have to be performed at a community level. Studies in Cambridge, The Gambia, and elsewhere indicate that the impact of variations in nutrient intake on lactational performance is limited: over the ranges normally found in developed and developing countries milk output does not vary in relation to energy intake, and effects of nutrient intake on milk quality are restricted to increases in vitamin content after appropriate supplementation.