Changes in Glial Fibrillary Acidic Protein-Immunoreactive Astrocytes in the Prefrontal Cortex of the Male Rat following Chronic Khat Use.

Background: Long-term khat consumption is associated with significant neurocognitive changes, which have been elucidated in behavioral studies. With current research showing the centrality of astrocytes and other glial cells in neuronal signaling, there is possibility that these cells are also affected by chronic khat use. There is little literature on the structural changes in the prefrontal cortex neuronal and astrocytic cytoarchitecture and morphometry in chronic khat users. Objective: The objective of this study was to describe the changes in astrocyte morphometry and structure in rats after long-term use of khat (miraa). Materials and Methods: Adult male Wistar rats, aged 2-3 months, weighing 200-300 g were randomized into four groups of 10 each (control, Group 1, Group 2, and Group 3) to correspond with those used as controls and those that received 500 mg/kg, 1000 mg/kg, and 2000 mg/kg body weight khat extracts, respectively. Fresh khat leaves were purchased from Maua market in Meru, and crude extract was prepared using lyophilization. The control rats were fed on normal diet, while the experimental groups were fed on normal diet and khat extracts using oral gavage for 6 weeks. The animals were sacrificed and their brains were removed. We performed immunohistochemical visualization of astrocytes using glial fibrillary acidic protein. Photomicrographs of the stained sections were transferred to ImageJ Fiji software to study the astrocyte density and astrocytic processes. We used Kruskal-Wallis test to correlate the four animal groups in terms of astrocyte densities. Results: We observed an increase in the average number of astrocytes with increasing doses of khat compared to controls, with those in Group 3 (2000 mg/kg) having an exuberant reactive astrocytosis. Further, escalating khat doses resulted in increased glial fibrillary acidic protein immunoreactivity in the nuclei and astrocytic processes, gliotic changes, and increased complexity of astrocytic processes. Conclusion: Chronic khat use, especially at high doses, results in reactive astrocytosis and astrogliosis, which may be part of the mechanisms involved in the cognitive changes associated with its use.

Effect of a Dose-Dependent Administration of Binge Alcohol on the Mandible in the Adolescent Sprague Dawley Rat

SUMMARY: Binge drinking in adolescents has a negative effect on the developing skeleton and the attainment of peak bone mass. Our study aimed to examine the effect of binge drinking on the growth and functional integrity of the adolescent Sprague Dawley rat mandible and to determine if a dosage of 1.5 g/kg is sufficient to produce a binge-model of consumption. A total of eight 7-week-old adolescent (male) Sprague Dawley rats were randomly placed into 4 groups with two rats each: 1-week alcohol-exposed rats, 1-week pair- fed control rats, 4-week alcohol-exposed rats and 4-week pair-fed control rats. The alcohol exposed groups were administered a single daily dose via oral gavage of 1.5 g/kg of 20 % alcohol 3 days a week (alternate days) for 7 or 28 days. The pair-fed control groups were administered a caloric equivalent dose of maltose dextrin via oral gavage on the same days as the alcohol-exposed rats. The one-week alcohol exposed, and control rats were terminated on day 7 and the four-week alcohol exposed and control rats on day 28. The mandibles were dissected out and osteometric measurements determined using a digital vernier caliper. Bones were scanned using a 3D-microCT scanner (Nikon XTH 255L). Biomechanical tests were done using a Shimadzu universal testing machine. Differences observed were regarding mandibular osteometry, which showed a reduced height in the central portion of the alveolar bone (Al'-Me), and an increase in the height of the condylar head (Cd-Ag) in the 1-week alcohol-exposed rats when compared to the 1-week pair-fed control rats. No other differences were noted. Lack of significant changes seen between the alcohol and pair-fed control groups in both acute binge and chronic binge exposed rats is likely due to the low dose of alcohol administered to the rats in the study thus a higher dose is proposed.

El consumo excesivo de alcohol en adolescentes tiene un efecto negativo en el desarrollo del esqueleto y en la consecución de la masa ósea máxima. Nuestro estudio tuvo como objetivo examinar el efecto del consumo excesivo de alcohol sobre el crecimiento y la integridad funcional de la mandíbula de la rata adolescente Sprague Dawley y determinar si una dosis de 1,5 g/kg es suficiente para producir un modelo de consumo compulsivo. Un total de ocho ratas Sprague Dawley adolescentes (machos) de 7 semanas de edad se colocaron aleatoriamente en 4 grupos con dos ratas cada uno: ratas expuestas al alcohol durante 1 semana, ratas de control alimentadas en parejas durante 1 semana, ratas expuestas al alcohol durante 4 semanas, y ratas de control alimentadas en parejas durante 4 semanas. A los grupos expuestos al alcohol se les administró una dosis única diaria mediante sonda oral de 1,5 g/kg de alcohol al 20 % 3 días a la semana (días alternos) durante 7 o 28 días. A los grupos de control alimentados por parejas se les administró una dosis calórica equivalente de maltosa dextrina mediante sonda oral los mismos días que a las ratas expuestas al alcohol. Las ratas expuestas al alcohol durante una semana, las ratas de control al día 7, las ratas expuestas al alcohol durante cuatro semanas y las ratas de control al día 28. Se diseccionaron las mandíbulas y se determinaron las mediciones osteométricas utilizando un calibre vernier digital. Los huesos se escanearon utilizando un escáner 3D-microCT (Nikon XTH 255L). Las pruebas biomecánicas se realizaron utilizando una máquina de pruebas universal Shimadzu. Las diferencias observadas se relacionaron con la osteometría mandibular, que mostró una altura reducida en la porción central del hueso alveolar (Al'-Me) y un aumento en la altura de la cabeza condilar (Cd-Ag) en las ratas expuestas al alcohol durante una semana, en comparación con las ratas control alimentadas en parejas durante una semana. No se observaron otras diferencias. La falta de diferencias significativas entre los grupos de alcohol y de control alimentados en parejas expuestas a ebriedad aguda y ebriedad crónica, probablemente se deba a la baja dosis de alcohol administrada a las ratas en el estudio, por lo que se propone una dosis más alta.

Topographic and Structural Anatomy of the Suspensory Ligament of the Penis: Implications for Phalloplasty.

BACKGROUND: The suspensory ligamentous system of the penis supports the penis when erect and plays a key role during coitus. These ligaments, which are prone to injury during coitus, are clinically important in penile reconstruction procedures. OBJECTIVES: The current study investigated the macro- and microanatomy of the suspensory ligamentous system of the penis to determine the origin, course, insertion, dimensions, and tissue composition of these ligaments, knowledge of which is vital for successful penile reconstruction procedures. METHODS: The study utilized a total of 49 cadavers. Gross anatomy dissection, MRI, and histological staining were performed to elucidate the topography, dimensions, and tissue composition of the suspensory ligaments of the penis. RESULTS: Three ligaments were observed to form the suspensory ligamentous system of the penis. The most superficial is the fundiform ligament, which consists of superficial bundles and deep median bundles, with the former arising from the Scarpa's fascia and the latter arising from the linea alba of the anterior abdominal wall; both inserted into the superficial fascia of the penis. The suspensory ligament of the penis arose from the pubic symphysis and inserted into the deep fascia (Buck's fascia) of the penis. The arcuate ligament arose from the body of the pubis and pubic symphysis and inserted into the Buck's fascia. The ligaments were determined to consist of adipose tissue, collagen fibers, elastic fibers and reticular fibers, in varying proportions. CONCLUSIONS: The suspensory ligaments of the penis exhibit a fan-like structure on the penis that allows the forward movement of the penis as a result of engorgement of the erectile bodies while simultaneously offering support.

Neurogenesis and Viral Infection.

Neural stem cells (NSCs) are multipotent stem cells that reside in the fetal and adult mammalian brain, which can self-renew and differentiate into neurons and supporting cells. Intrinsic and extrinsic cues, from cells in the local niche and from distant sites, stringently orchestrates the self-renewal and differentiation competence of NSCs. Ample evidence supports the important role of NSCs in neuroplasticity, aging, disease, and repair of the nervous system. Indeed, activation of NSCs or their transplantation into injured areas of the central nervous system can lead to regeneration in animal models. Viral invasion of NSCs can negatively affect neurogenesis and synaptogenesis, with consequent cell death, impairment of cell cycle progression, early differentiation, which cause neural progenitors depletion in the cortical layer of the brain. Herein, we will review the current understanding of Zika virus (ZIKV) infection of the fetal brain and the NSCs, which are the preferential population targeted by ZIKV. Furthermore, the potential neurotropic properties of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may cause direct neurological damage, will be discussed.

Distribution of variations in anatomy of the circle of Willis: results of a cadaveric study of the Malawian population and review of literature.

INTRODUCTION: the circle of Willis is an anatomical structure of clinical importance particularly in the evaluation of neurovascular diseases. Individuals show considerable variations in the anatomical configuration of the circle of Willis. A cross-sectional study was conducted to determine the distribution of morphological variations of the circle of Willis in Malawians and compare with other ethnic groups. METHODS: brains were collected from twenty-four recently deceased black Malawians during autopsy at Queen Elizabeth Central Hospital, a referral teaching hospital in Blantyre, Malawi and fixed in 10% buffered formalin. Digital images of the interpeduncular region (exposing the circle of Willis) were taken with an 18.4 megapixels camera from the base of the brain. Whole-circle and segmental parameters of the circle of Willis were assessed using the Osiris computer programme and classified based on a 22-type classification scheme. RESULTS: the following morphological variations were observed: hypoplasia, aplasia, asymmetry and accessory vessels. Typical circle of Willis was seen in 26% of the cases. Only six of the original twenty-two types were observed. Consistent with most previous studies, types 1, 3, 4, 6, 8 and 9 were common while types 10-22 were rare. Three variants not previously described in the original scheme (unilateral PcoA aplasia, AcoA duplication, and PcoA aplasia with contralateral PcoA hypoplasia) were observed in this study. CONCLUSION: anatomical variations of the circle of Willis in Malawians seem to be distributed in similar frequencies and patterns as in other more-diverse populations. Circle of Willis variants with potential predilection for atherogenesis and aneurysm formation exist in the Malawian population. These should be considered in clinical practice.

Coadministration of ARV (Atripla) and Topiramate disrupts quail cardiac neural crest cell migration.

INTRODUCTION: Congenital anomalies such as ventricular septal defects and truncus communis have been reported with the prenatal use of antiretroviral therapy. The mechanism of antiretroviral therapy teratogenicity is unclear and is therefore the focus of this study. Some human immunodeficiency virus patients on antiretrovirals are placed on antiepileptic drugs which are also teratogenic. The interactive effects arising from this therapeutic combination may affect their teratogenic propensity through their effects on neural crest cell migration. METHODS: Appropriately cultured neural crest cells from dissected neural tubes of 32-hr old quail embryos exposed to culture media containing peak plasma levels of Atripla, Topiramate and the combination of both were studied. Distance of migration of neural crest cells was measured using the migration assay and the cells were stained with rhodamine phalloidin to evaluate the cell actin. Also quail neural crest cells were brought into suspension and microinjected into chick hosts to determine the migration of the cells to the interventricular septum. RESULTS: Migration of cultured neural crest cells was extensive in the control cultures, but inhibited in the treated groups. The experimental cultures showed a disarray of actin cytoskeleton contrary to normal distribution of actin filaments in controls. Significantly, few quail neural crest cells migrated to the interventricular septum of chick host embryos compared to the control cultures. The coadministration of topiramate with antiretroviral therapy does not seem to affect the activity of the antiretroviral drug. CONCLUSION: These results indicate that Atripla and Topiramate cause ventricular septal defects by inhibiting the migration of cardiac neural crest cells.

Adult neurogenesis in the African giant rat (Cricetomysgambianus, waterhouse).

African giant rats (AGR) are large nocturnal rodents with well-developed olfactory abilities uniquely linked to cognition. The post natal proliferation of neurons (adult neurogenesis), is thought to play an important role in spatial memory and learning. Eighteen brains of the African giant rats (Cricetomys gambianus, Waterhouse) belonging to three age groups (neonates n = 6, juveniles n = 6 and adults n = 6) were examined by immunohistochemistry, using antibodies for proliferating cells (Ki-67), and immature neurons (Doublecortin, DCX). Mean brain weights were 0.40 ± 0.00 g; 4.48 ± 0.43 g and 5.48 ± 0.56 g for neonate, juvenile and adult brains respectively. Our results show positive cell proliferation in the subventricular (SVZ) zone of the lateral ventricle and in the dentate gyrus (DG) of the hippocampus but at low levels in adults compared to juveniles. Estimate of the mean total proliferative Ki-67 positive cells in the SVZ and DG in the neonates was 21145 ± 8395, and 11800 ± 1230; brains from juvenile AGRs, 45530 ± 13950 and 12480 ± 7860 and from adult brains, (6880 ± 340 and 1130 ± 150) respectively. Juvenile AGR in particular, stained positively in potential sites such as the piriform and somatosensory cortices, striatum and cerebellum. This intensity of the proliferating cells within the dentate gyrus in the juvenile and adult brains could be associated with a role in the cognitive functions of landmine detection and tuberculosis diagnosis after olfactory training of the African giant rat. The juvenile rats are proposed as the most suited for experimental research and olfactory training.

Histology and ultrastructure of transitional changes in skin morphology in the juvenile and adult four-striped mouse (Rhabdomys pumilio).

The four-striped mouse has a grey to brown coloured coat with four characteristic dark stripes interspersed with three lighter stripes running along its back. The histological differences in the skin of the juvenile and adult mouse were investigated by Haematoxylin and Eosin and Masson Trichrome staining, while melanocytes in the skin were studied through melanin-specific Ferro-ferricyanide staining. The ultrastructure of the juvenile skin, hair follicles, and melanocytes was also explored. In both the juvenile and adult four-striped mouse, pigment-containing cells were observed in the dermis and were homogeneously dispersed throughout this layer. Apart from these cells, the histology of the skin of the adult four-striped mouse was similar to normal mammalian skin. In the juvenile four-striped mouse, abundant hair follicles of varying sizes were observed in the dermis and hypodermis, while hair follicles of similar size were only present in the dermis of adult four-striped mouse. Ultrastructural analysis of juvenile hair follicles revealed that the arrangement and differentiation of cellular layers were typical of a mammal. This study therefore provides unique transition pattern in the four-striped mouse skin morphology different from the textbook description of the normal mammalian skin.