Neuronal injuries in cerebral infarction and ischemic stroke: From mechanisms to treatment (Review)

Abstract

Stroke is the leading cause of disabilities and cognitive deficits, accounting for 5.2% of all mortalities worldwide. Transient or permanent occlusion of cerebral vessels leads to ischemic strokes, which constitutes the majority of strokes. Ischemic strokes induce brain infarcts, along with cerebral tissue death and focal neuronal damage. The infarct size and neurological severity after ischemic stroke episodes depends on the time period since occurrence, the severity of ischemia, systemic blood pressure, vein systems and location of infarcts, amongst others. Ischemic stroke is a complex disease, and neuronal injuries after ischemic strokes have been the focus of current studies. The present review will provide a basic pathological background of ischemic stroke and cerebral infarcts. Moreover, the major mechanisms underlying ischemic stroke and neuronal injuries are summarized. This review will also briefly summarize some representative clinical trials and up-to-date treatments that have been applied to stroke and brain infarcts. Contents 1. Introduction 2. Pathophysiological processes of ischemia 3. Clinical management 4. Conclusion and future perspectives

Dysregulation of mTOR Signaling after Brain Ischemia

“…In this regard, some experimental evidence confirms this hypothesis [ 79 ]. The pharmacological induction of autophagy after ischemia using rapamycin reduces brain damage [ 73 , 82 , 83 , 84 ]. However, other results indicate that excessive autophagic flow aggravates ischemic damage [ 85 ].…”

“…To date, the only therapeutical intervention available to ameliorate ischemic damage is a reduction in neuronal injury via reperfusion using a thrombolytic agent (recombinant tissue plasminogen activator, tPA) or surgical removal of clots [ 84 ]. However, these strategies are very limited because they are only feasible within a short time window after ischemia onset due to the high risk of intracerebral hemorrhage, which would worsen the prognosis of the patient.…”

“…The first group is global ischemia (two- or four-vessel occlusion), which reproduces the impact of a cardiac arrest on the brain and affects the entire brain. The second group, called focal cerebral ischemia, mimics occlusion of a cerebral artery either by an embolus or local thrombosis, with middle cerebral artery occlusion (MCAo) being the most frequent [ 84 , 98 , 99 ]. MCAO models can be subdivided into two groups: transient MCAo (tMCAo) and permanent MCAo (pMCAo).…”

“…After 2 days of pMCAo, the inflammatory stage is established. Ischemia-induced cell death results in the release of damage-associated molecular patterns (DAMPs), thereby activating microglia to acquire a reactive phenotype [ 84 , 101 , 136 , 155 ]. Given the phagocytic capacity of microglia as scavengers, they are the first glial cells to respond to cerebral ischemia [ 156 ].…”

Progress in Isoindolone Alkaloid Derivatives from Marine Microorganism: Pharmacology, Preparation, and Mechanism

“…For instance, stroke is responsible for 5.2% of all mortalities in the world [26]. Most of them are ischemic strokes, which would trigger transient or permanent occlusion of cerebral vessels causing brain infarcts, cerebral tissue death, and focal neuronal damage after blocking for 6 h [27]. Therefore, the key to saving stroke patients is solving thromboembolism in an efficient way.…”