http://hdl.handle.net/123456789/53 2026-04-03T09:26:31Z 2026-04-03T09:26:31Z POPOOLA, ABDULGAFAR NIYI http://hdl.handle.net/123456789/1734 2024-04-18T09:01:58Z 2021-12-01T00:00:00Z

NEUROBEHAVIOURAL AND HISTOMORPHOLOGICAL CHANGES IN THE HIPPOCAMPUS AND CEREBELLUM OF WISTAR RATS TREATED WITH ARTESUNATE AND AMODIAQUINE POPOOLA, ABDULGAFAR NIYI Artemisinin-based Combination Therapy (ACT) is among the best chemotherapeutic options for malaria. Artesunate (AS) + Amodiaquine (AQ) is a commonly used ACT in Nigeria, having good efficacy but with side effects involving memory loss and impaired motor coordination ranging from acute to chronic. Reports on acute effect of AS+AQ on the cerebellum and hippocampus are controversial and there is dearth ofinformation on its delayed effect on these brain areas. This study was designed to evaluate the effects of AS+AQ administration on neurobehaviour and morphology of the hippocampus and cerebellum in Wistar rat after three-day acute treatment. Eighty adult male Wistar rats (120±5g) were divided into 4 groups (n=20): Group A: Control (CT: Distilled water), Group B: AS (4mg/kg), Group C: AQ (10mg/kg) and Group D: AS (4mg/kg) + AQ (10mg/kg). Drugs were administered orally, once daily for 3 days and animals monitored for 14 days. Weights of the animals were recorded. Spatial memory and motor function were evaluated using Morris water-maze and fore limb grip tests, respectively. Animals were sacrificed by cervical dislocation on the 4 th and 15th day. Collected blood samples were analysed for full blood count. Excised cerebelli and hippocampi were processed for lipid peroxidation, biochemical markers of oxidative stress including nitric oxide (NO). Histological (Haematoxylin & Eosin) and immunohistochemical techniques including Glial Fibrillary Acid Protein (GFAP) and Cyclo-oxygenase II (COX-2) were also carried out. Data were analysed by ANOVA at α0.05. There was no significant variation in weight, neurobehavioural, haematological, biochemical, morphological and immunohistochemical parameters between all groups for the 3 days. At 14 days, AQ group had significant weight loss (30.40%) compared with the CT group and significantly increased swimming time (22.86±2.70s) compared with the CT group (4.14±0.74s). The AS (8.00±1.11s) and AQ (7.43±0.92s) had significantly decreased grip time compared with CT (17.86±1.22s); AQ significantly increased RBC (8.30±0.13/µL) and PCV (57.00±1.30%) compared with CT (RBC: 6.90±0.31/µL, PCV: 45.80±1.36%). Lipid peroxidation (per nmmol/g) increased significantly in AS (233.07±2.26), AQ (257.14±2.06) and AS+AQ (223.32±1.99) compared with CT (180.33±0.47). Ditto for NO (/µm/mg) (CT: 455.49±3.93, AS: 472.32±0.91, AQ: 525.74±10.11, AS+AQ: 480.95±2.917). The cerebellar Purkinje cell population was significantly reduced in the AS (2.50±0.29) and AQ (1.25±0.25) groups compared with CT (5.75±0.48), indicating pyknosis. Hippocampal Cornus Ammonis 1 cells were significantly depopulated in the AS (10.75 ±0.48) and AQ (7.25±0.48) groups compared to the CT (13.25±0.25) group, also indicating pyknosis. The GFAP expressions (per %area) significantly increased in the cerebelli of AS (55.95±1.85) and AQ (57.79±1.85) groups compared with CT (23.60±3.02) and in AS (76.81±7.19) and AQ (83.71±3.78) groups of hippocampus compared with CT (55.19±3.86), indicating astrogliosis. Compared with CT (59.36±5.61), AS (83.99±5.18) and AQ (88.32±0.88) had significantly increased hippocampal COX-2 expression per %area, indicating inflammation. Neurobehavioural and morphological changes due to Artesunate and Amodiaquine administration in Wistar rats were significant only after 14 days.

2021-12-01T00:00:00Z ONATOLA, OLUBUNMI AYOBAMI http://hdl.handle.net/123456789/1484 2022-02-23T07:40:41Z 2021-07-01T00:00:00Z

THE PROLIFERATION AND MIGRATION OF GRANULE CELLS IN THE CEREBELLAR CORTEX OF NEONATAL SWISS MICE FOLLOWING MATERNAL TRYPTOPHAN ADMINISTRATION ONATOLA, OLUBUNMI AYOBAMI The External Granular Layer (EGL) of the cerebellar cortex is a region of proliferative cells which migrate to their last position in the internal granular cell layer of the cerebellum. Delay in the transit of cells from the EGL has been associated with deficiency of tryptophan, an amino acid, which is important in cerebellar maturation and in the disappearance of the EGL. The role of tryptophan in the development of the cerebellar cortex has not been fully looked at. In this study, the profile of the EGL in neonatal mice was examined following maternal administration of tryptophan. Forty pregnant female Swiss mice weighing between 28 and 45g were allotted to four groups (n=10). The day the mice delivered was postnatal day (PND) 0. Control group (Group I) received distilled water, Groups II-IV orally received 100, 200 and 300mg/kg body weight solution of tryptophan, respectively. Dams in each group received a daily dose of tryptophan postpartum for 0,7,14,21 days and the pups (n=5) were sacrificed after the last dose. In the pups, Brain Weight (BW) and Cerebellar Weight (CW) were measured by a weighing scale; Brain Tryptophan (BT) and Serum Tryptophan (ST) levels were measured by spectrophotometry. The cerebella were fixed in 10% formalin, coronal sections taken at the paraflocculus were stained with haematoxylin and eosin for estimation of cerebellar cortical layer width, neuronal cell counts and mitotic index. Other coronal sections were stained with cresyl violet for radially oriented granule cells; modified Golgi stain for dendritic arborization of Bergmann glial cells; ki-67 immunostaining for cell proliferation and Bcl-2 immunostaining for apoptotic cells. Data were analysed using ANOVA at α0.05. On PND7, BW of GroupII (0.25 ± 0.07g) was significantly greater than Group I(0.20 ± 0.03g), GroupIII (0.20±0.05g) and GroupIV (0.17±0.03g) and CW of GroupII (0.06±0.01g) was greater than GroupI (0.05±0.01), GroupIII (0.05±0.01) and GroupIV (0.03±0.07g). External granular layer width of GroupI (0.11±0.00mm) was less than GroupII (0.13±0.05mm), GroupIII (0.13±0.13mm) and GroupIV (0.13±0.02mm) on PND14. Percentage BT in GroupII (9±2x10-4%) and GroupIII (12±2x10-4%) was significantly higher than GroupI (8±2 x10-4%) and GroupIV (7±2 x10-4%). Serum tryptophan in GroupII (0.020±0.012%) was significantly higher than GroupI (0.005±0.002, GroupIII (0.011±0.005) and GroupIV (0.002±0.001%) on PND21. The EGL density of GroupIV (34.0±5.15mm2) was higher than GroupI (23.6±8.02mm2), GroupII (30.7±2.5mm2) and GroupIII (31.4±2.5mm2). Mitotic index was significantly higher in GroupIV (11.8%) than others (6.6,7.9,6.2%). Number of radially oriented granule cells was significantly higher in GroupII (2.6±0.62; 2.98±1.02), GroupIII (2.9±0.93; 2.3±0.42) and GroupIV (2.7±0.29; 3.1±0.86) than GroupI (1.67±0.48; 1.28±0.43) on PND7 and 14. The EGL persisted in GroupII pups compared to others on PND21 and there were more Bergmann glial cytoplasmic processes in GroupII than in other groups. Percentage positivity of ki-67 cells was significantly increased in GroupII and GroupIII on PND7 and 14. However, the percentage positivity of Bcl-2 was significantly increased in GroupII on PND7. Low dose tryptophan prevented the early loss of cells in the EGL which can be a potential site for adult neurogenesis and a source of stem cells.

2021-07-01T00:00:00Z