title: Multidirectional inhibition of cortico-hippocampal neurodegeneration by kolaviron treatment in rats.
abstract: Earliest signs of neurodegenerative cascades in the course of Alzheimer's disease (AD) are seen within the prefrontal cortex (PFC) and hippocampus, with pathological evidences in both cortical structures correlating with manifestation of behavioural and cognitive deficits. Despite the enormous problems associated with AD's clinical manifestations in sufferers, therapeutic advances for the disorder are still very limited. Therefore, this study examined cortico-hippocampal microstructures in models of AD, and evaluated the possible beneficial roles of kolaviron (Kv)-a biflavonoid complex in rats. Nine groups of rats were orally exposed to sodium azide (NaN3) or aluminium chloride (AlCl3) solely or in different combinations with Kv. Sequel to sacrifice and transcardial perfusion (using buffered saline then 4% paraformaldehyde), PFC and hippocampal tissues were harvested and processed for: spectrophotometric assays of oxidative stress and neuronal bioenergetics parameters, histological demonstration of cytoarchitecture and immunohistochemical evaluation of astrocytes and neuronal cytoskeleton. Results showed alterations in mitochondrial functions, which led to compromised neuronal antioxidant system, dysfunctional neural bioenergetics, hypertrophic astrogliosis, cytoskeletal dysregulation and neuronal death within the PFC and hippocampus. These degenerative events were associated with NaN3and AlCl3toxicity in rats. Furthermore, Kv inhibited cortico-hippocampal degeneration through multiple mechanisms that primarily involved halting of biochemical cascades that activate proteases which destroy molecules expedient for cell survival, and others that mediate a program of cell suicide in neuronal apoptosis. In conclusion, Kv showed important neuroprotective roles within cortico-hippocampal cells through multiple mechanisms, and particularly has prominent prophylactic activity than regenerative potentials.
authors.affiliation: Division of Neurobiology, Department of Anatomy, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. olajide.oj@unilorin.edu.ng.
authors.forename: Olayemi Joseph
authors.initials: OJ
authors.lastname: Olajide
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, University of Ilorin, Ilorin, Nigeria.|Central Research Laboratories Ltd, 132b University Road, Ilorin, Nigeria.
authors.forename: Nnaemeka Tobechukwu
authors.initials: NT
authors.lastname: Asogwa
authors.affiliation: Division of Neurobiology, Department of Anatomy, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria.
authors.forename: Blessing Oluwapelumi
authors.initials: BO
authors.lastname: Moses
authors.affiliation: Division of Neurobiology, Department of Anatomy, Faculty of Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria.
authors.forename: Christiana Bidemi
authors.initials: CB
authors.lastname: Oyegbola
mesh_terms: D000077410:Aluminum Chloride; D017607:Aluminum Compounds; D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002712:Chlorides; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D019810:Sodium Azide; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D017607:Aluminum Compounds; D000975:Antioxidants; D002712:Chlorides; D005419:Flavonoids; D018696:Neuroprotective Agents; D010936:Plant Extracts; D000077410:Aluminum Chloride; D019810:Sodium Azide; D013482:Superoxide Dismutase; C045492:kolaviron
keywords: Alzheimer’s disease; Astrogliosis; Cytoskeleton; Neural bioenergetics; Oxidative stress