Effect of exogenous melatonin administration on transient global cerebral ischemia and adult neurogenesis

Ph.D., Faculty of Science, University of the Witwatersrand, 2011This study investigated the effect of exogenous melatonin administration on transient global cerebral ischemia and adult neurogenesis in adult male Sprague- Dawley rats. It also determined serum melatonin concentrations in all the experimental groups and established any effect of melatonin on estimated total granule cell numbers. Adult male Sprague-Dawley rats were divided into eight groups with each group consisting of 6 rats (n = 6). Post-induction time durations of 72 hours and 7 days was used. Single dose of 5 mg/kg exogenous melatonin was administered at each phases of 30 minutes before and after a 10 minutes transient bilateral occlusion of the common carotid arteries in the different groups, followed by reperfusion. Rats were anesthetized with 20 mg/kg of ketamine and 2.5 mls of blood was collected via cardiac puncture for estimation of serum melatonin concentration using commercially prepared radioimmunoassay ELISA kit. Free floating brain sections cut at 50 μm were immunostained for Ki-67, marker for proliferating cells. The total granule cell number in the dentate gyrus was estimated using the optical fractionator method on plastic embedded brain sections. Mean melatonin concentration (pg/mol) was 268.54 ± 28.73 (72 hours) and 277.83 ± 28.73 (7 days) compared to the sham control; 266.94 ± 37.6 and non surgical 262.96 ± 23.85 respectively. Differences in the concentration were not statistically significant (P<0.05). Histological finding indicated neuropil disruption with potentiation of restoration as the post ischemia days progressed in the melatonin administered groups. The estimated total granule cell number in the dentate gyrus of the hippocampus was not affected by exogenous melatonin administration. However, there was potentiation in proliferations of the neurogenic niche in the dentate gyrus of the hippocampus demonstrating a very strong indications that melatonin enhanced the generations of proliferating cells in adult male Sprague-Dawley rats

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

Pro-Neurogenic and Antioxidant Efficacy of Nigella sativa Oil Reduced Vulnerability Cholinesterase Dysfunction and Disruption in Amygdala-Dependent Behaviours in Chlorpyrifos Exposure

Background: Organophosphorus Pesticides (OPs) are compounds with irreversible cholinesterase activity which induce cholinergic neurotoxicity, but still remain a widely used pesticide in household and agriculture. Aim and Objectives: This study investigated the efficacy of a natural antioxidant Nigella sativa Oil (NSO) against Chlorpyrifos (CPF) induced oxidative stress and implications on emotionality behaviours. Material and Methods: Thirty-two adult Wistar rats were randomly divided into four groups, and exposed to (1 ml/kg b w) of normal saline, (14.9 mg/kg b w) of CPF, (14.9 mg/kg b w) of CPF plus (1 ml/kg b w) of NSO and (1 ml/kg b w) of NSO respectively for 14 consecutive days. Body weight were recorded at day 1 and 15 of the experiment, the rats were exposed to trials in both Open Field Test (OFT) and Elevated Plus Maze (EPM) to asses anxiety-like behaviours and fear related learning respectively on the 13th day. Rats were euthanized by the 15th day, the brains excised, and the amygdala area of brains were removed, homogenized to analyse for total Reactive Oxygen Species (ROS), Nitrous Oxide (NO) levels and Acetylcholinesterase (AChE) activities, while the other three were processed for histology (Nissl stain) and Proliferative marker (Ki67 immunohistochemistry). Results: Repeated CPF exposure caused an increase in NO and ROS levels, reduction in AChE activities and a loss in the neurogenic cells in the amygdala. It was also a prolonged freezing period, centre squares avoidance and delayed transfer latency with CPF exposure. However, NSO prevented the overproduction of ROS and NO, and markedly reactivated AChE activities in the amygdala either with or without CPF exposure. NSO treatment was also, able to preserve neurogenic cells in the amygdala and subsequently improved amygdala-dependent behaviours in the treated rats. Conclusion: The antioxidant efficacy of NSO could be efficacious in CPF induced neuro-cognitive toxicity in rats

Placental Anthropometric Features: Maternal and Neonate Characteristics in North Central Nigeria

The objectives of the study were to determine placental weight as well as factors associated with low placental weight and to determine its impact on some anthropometrical parameters in the newborn. A total of 300 freshly delivered placentas were examined in this longitudinal-prospective study. Sobi Specialist Hospital, Alagbado, Ilorin, and Surulere Medical Centre, Eruda, Ilorin, were used for sample collections. Informed consent was obtained from patients and institutional ethical clearance was obtained from Kwara State Ministry of Health (MOH/KS/ECI/777/82). Semistructured questionnaire was used to gather data on the patients and newborns demographic indices. Analysis of variance, Student’s t-test, regression analysis, and Pearson moment correlation statistical analysis were employed to analyze the data. The mean wet placental weight for normal pregnancies was 529 g (SD = 84.01). Placental weight to birth weight ratio of 1 : 5.83 was generated, 529 g impact on newborn head circumference (mean: male = 35.30 cm, female = 34.90 cm) having a linear correlation. Regression analysis showed negative association between female babies (2.99 kg) placental weight (r=0.369; P≤0.05), birth weight, and cord length (mean = 58.4 cm). Placental weight correlation with male newborn weight (3.14 kg) had placental birth weight ratio of 0.679 between 90th and 10th percentile P<0.05 with head circumference (r=0.473, P<0.05), lower limit placental diameter 22.80 ± 1.76 cm (SD = 4.8), BMI ≤ 19.50, and Apgar score of 7/10. It is concluded that blood holding capacity of the placenta (relative to weight) and the maternal-dietary have influence on placental weight. Differences in hormonal environment in utero and pathologic adaptation of placenta, due to racial factors, significantly contributed to the size of newborn baby

Behavioural Patterns and Corticosterone Levels Induced by Chronic Psychosocial Stress in the Four-Striped Mice (Rhabdomys pumilio)

This study presents, findings from investigations of the influence of chronic psychosocial stress on behavioural patterns and corticosterone levels in the four-striped mice, Rhabdomys pumilio. A modified resident-intruder paradigm was adopted in the study and involved the introduction of an intruder mouse (40-80 g) to a resident mouse (90-175 g) for 1 h for 5 consecutive days. Intruders interacted with different residents each day and behavioural responses were recorded. To determine if the resident-intruder paradigm induced an adrenocortical stress response, blood samples were collected after the last day of the paradigm via cardiac puncture from the control and intruder mice. The frequency of aggression (90±18 events dayG) received 1 from the residents and upright defense exhibited by intruders (43±9 events dayG) differed significantly over 1 repeated test days, however, there were no significant differences in the frequency of the resident climbing on the intruder’s cage (104±21 events dayG) Elevations of corticosterone levels were evident in the stressed mice. 1 Our data indicate that behavioural and neuroendocrinological responses may have important implications in the four-striped mice and in the understanding of psychiatric disorders

Effect of melatonin on neuronal nitric oxide synthase expressing cells in the brain following global cerebral ischemia

Nitric oxide can be either neuroprotective or neurotoxic depending on which isoform is expressed during global cerebral ischemia. The chronological and spatial distribution and expression of neuronal nitric oxide synthase cells in the brain following ischemia and melatonin administration was studied in Sprague-Dawley rats. Global cerebral ischemia was induced by common carotid artery occlusion for 10 min followed by reperfusion. The rats were divided into three experimental groups. One group received 5 mg kg melatonin 30 min before ischemia, another group received the same dose of melatonin post-ischemia and a third NO ischemia NO melatonin control group. All animals were euthanized 72 h post ischemia, perfusion-fixed with 4% paraformaldehyde in phosphate buffer and the brains removed. Immunopositive neuronal Nitric Oxide Synthase (nNOS) expression was observed in the cerebral cortex, putamen, caudate nucleus, substantia reticularis olfactory bulb, nucleus caudatus, hippocampus and subcallosal cortex. No nNOS positive cells were observes in the cerebellum in any group. The nNOS expression was higher in the noischemia NO melatonin group (220) followed by the post-ischmia melatonin melatonin group (179) and the lowest (148) in the pre-ischemia melatonin group. A neuroprotective role by melatonin in the post-ischemic phase seems to be the mechanism of action associated with NOS activity in ischemic brain injur

Behavioural Patterns and Corticosterone Levels Induced by Chronic Psychosocial Stress in the Four-Striped Mice (Rhabdomys pumilio)

This study presents, findings from investigations of the influence of chronic psychosocial stress on behavioural patterns and corticosterone levels in the four-striped mice, Rhabdomys pumilio. A modified resident-intruder paradigm was adopted in the study and involved the introduction of an intruder mouse (40-80 g) to a resident mouse (90-175 g) for 1 h for 5 consecutive days. Intruders interacted with different residents each day and behavioural responses were recorded. To determine if the resident-intruder paradigm induced an adrenocortical stress response, blood samples were collected after the last day of the paradigm via cardiac puncture from the control and intruder mice. The frequency of aggression (90±18 events dayG) received 1 from the residents and upright defense exhibited by intruders (43±9 events dayG) differed significantly over 1 repeated test days, however, there were no significant differences in the frequency of the resident climbing on the intruder’s cage (104±21 events dayG) Elevations of corticosterone levels were evident in the stressed mice. 1 Our data indicate that behavioural and neuroendocrinological responses may have important implications in the four-striped mice and in the understanding of psychiatric disorders

Effect of melatonin on neuronal nitric oxide synthase expressing cells in the brain following global cerebral ischemia

Nitric oxide can be either neuroprotective or neurotoxic depending on which isoform is expressed during global cerebral ischemia. The chronological and spatial distribution and expression of neuronal nitric oxide synthase cells in the brain following ischemia and melatonin administration was studied in Sprague-Dawley rats. Global cerebral ischemia was induced by common carotid artery occlusion for 10 min followed by reperfusion. The rats were divided into three experimental groups. One group received 5 mg kg melatonin 30 min before ischemia, another group received the same dose of melatonin post-ischemia and a third NO ischemia NO melatonin control group. All animals were euthanized 72 h post ischemia, perfusion-fixed with 4% paraformaldehyde in phosphate buffer and the brains removed. Immunopositive neuronal Nitric Oxide Synthase (nNOS) expression was observed in the cerebral corte