Cerebral ischemia is a result of insufficient blood flow to the brain. It leads to limited supply of oxygen and other nutrients to meet metabolic demands. These phenomena lead to brain damage. There are two types of cerebral ischemia: focal and global ischemia. This condition has significant impact on patient’s health and health care system requirements. Animal models such as transient occlusion of the middle cerebral artery and permanent occlusion of extracranial vessels have been established to mimic the conditions of the respective type of cerebral ischemia and to further understand pathophysiological mechanisms of these ischemic conditions. It is important to understand the pathophysiology of cerebral ischemia in order to identify therapeutic strategies for prevention and treatment. Here, we review the neuropathologies that are caused by cerebral ischemia and discuss the mechanisms that occur in cerebral ischemia such as reduction of cerebral blood flow, hippocampal damage, white matter lesions, neuronal cell death, cholinergic dysfunction, excitotoxicity, calcium overload, cytotoxic oedema, a decline in adenosine triphosphate (ATP), malfunctioning of Na+/K+-ATPase, and the blood-brain barrier breakdown. Altogether, the information provided can be used to guide therapeutic strategies for cerebral ischemia.
The aging population increases steadily because of a healthy lifestyle and medical advancements in healthcare. However, Alzheimer’s disease (AD) is becoming more common and problematic among older adults. AD-related cases show an increasing trend annually, and the younger age population may also be at risk of developing this disorder. AD constitutes a primary form of dementia, an irreversible and progressive brain disorder that steadily damages cognitive functions and the ability to perform daily tasks. Later in life, AD leads to death as a result of the degeneration of specific brain areas. Currently, the cause of AD is poorly understood, and there is no safe and effective therapeutic agent to cure or slow down its progression. The condition is entirely preventable, and no study has yet demonstrated encouraging findings in terms of treatment. Identifying this disease’s pathophysiology can help researchers develop safe and efficient therapeutic strategies to treat this ailment. This review outlines and discusses the pathophysiology that resulted in the development of AD including amyloid-β plaques, tau neurofibrillary tangles, neuroinflammation, oxidative stress, cholinergic dysfunction, glutamate excitotoxicity, and changes in neurotrophins levels based on the literature search from Scopus, PubMed, ScienceDirect, and Google Scholar. Potential therapeutic strategies are discussed to provide more insights into AD mechanisms by developing some possible pharmacological agents for its treatment.
Public interest statement Plants are rich source of chemical diversity and provides the initiation platform for any drug discovery programme. Identifying the potential plants with anti-cholinesterase activity provides a platform to develop more e ective drugs for treatment of AD.
Vascular dementia (VaD), is one of the most common types of dementia in the ageing population, initiated by chronic cerebral hypoperfusion (CCH). At present, effective therapeutic approaches to cure VaD are still missing. Cholinergic system dysfunction in the central nervous system (CNS) has been recognised as one of the main reasons for learning and memory impairment in VaD patients. Therefore, medications that restore the level of acetylcholine (ACh) neurotransmitter by inhibiting cholinesterase activity were proposed as a potential candidate to treat VaD patients. Permanent occlusion of bilateral common carotid arteries (POBCCA) surgery method was performed to develop CCH model in rats. The present study evaluated the anti-cholinesterase activity of three Malaysian plant methanol leaf extracts in vitro and further validated its cognitive-enhancing effects in vivo using POBCCA rats. The selected plant extracts were Coccoloba uvifera (stems), Mimusops elengi (leaves) and Syzygium aqueum (leaves). The in vitro anti-cholinesterase activities of these plants were determined using Ellman's method. The effects of selected plant extracts (100 and 200 mg/kg, p.o.) on learning and memory functions were evaluated using a series of behavioural tests. All the selected plant extracts exhibited good anti-acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities in vitro, with IC50 ranging from 3.67 to 16.04 and 5.6 to 13.95 µg/mL, respectively. Extracts of S. aqueum (200 mg/kg) improve both short- and long-term recognition memories, whereas M. elengi and S. aqueum (200 mg/kg) extracts improve spatial learning. None of the extracts impaired motor and exploratory functions in POBCCA rats. In conclusion, methanol extracts of C. uvifera, M. elengi and S. aqueum showed good anti-cholinesterase activity in vitro. However, only M. elengi and S. aqueum improve learning and memory function in POBCCA rats.
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