Insights into the neuropathology of cerebral ischemia and its mechanisms

Abstract

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.

In vitro anti-cholinesterase activity and in vivo screening of Coccoloba uvifera, Mimusops elengi and Syzygium aqueum extracts on learning and memory function of chronic cerebral hypoperfusion rat

“…The hippocampus plays a vital role in encoding, and newly acquired information is temporarily stored as STM within the hippocampus (Macdonald et al, 2013) before being transmitted to the cerebral cortex for longterm storage (Ivanco & Racine, 2000;Williams et al, 2004;Mehta, 2018). CCH induced neuronal cell death in the hippocampus, and cerebral cortex have been pointed out to disrupt CNS network signalling (e.g., glutamatergic and cholinergic) and leads to learning and memory dysfunction in POBCCA rats (Saxena et al, 2015;Ahad et al, 2020). Interestingly, treatment of S. aqueum extract significantly ameliorates short-and long-term recognition memory in POBBCA rats.…”

Xanthone-enriched fraction of Garcinia mangostana and α-mangostin improve the spatial learning and memory of chronic cerebral hypoperfusion rats

“…Hippocampus is the key structure for spatial learning and memory, and it is also one of the most susceptible regions to hypoperfusion, particularly in CA1 area. [ 31,32 ] After 2VO was induced, neuronal cells in hippocampus undergo apoptosis and result in progressive cell death. [ 32 ] Hence, defect in spatial learning of 2VO can be related to neuronal loss in hippocampus.…”

“…[ 31,32 ] After 2VO was induced, neuronal cells in hippocampus undergo apoptosis and result in progressive cell death. [ 32 ] Hence, defect in spatial learning of 2VO can be related to neuronal loss in hippocampus. When 2VO rats received XEFGM (100 mg/kg) and α‐MG (25, 50 mg/kg) during the 5 days post‐training sessions in spatial learning task, their spatial learning ability was improved.…”

Role of Phytocompounds En Route Blood-brain Barrier in Cerebral Ischemia

“…Activation of genes of pro-inflammatory mediators such as chemokines, adhesion molecules, cytokines and inflammatory enzymes is mediated by activated Signal transducer and activator of transcription (STAT3) and nuclear factor-κB (NF-κB) [1]. Acute neuroinflammation beginning within hours of the ischemic insult and the oxidative stress that follows, cause most of the brain injury including neuronal damage, and cerebral edema, cognitive impairments and faulty neuronal signalling which may lead to permanent brain damage [2]. The equilibrium of ionic gradients across the membrane is disrupted.…”