Extracellular matrix metalloproteinase inducer in brain ischemia and intracerebral hemorrhage

Abstract

Increasing evidence from preclinical and clinical studies link neuroinflammation to secondary brain injury after stroke, which includes brain ischemia and intracerebral hemorrhage (ICH). Extracellular matrix metalloproteinase inducer (EMMPRIN), a cell surface transmembrane protein, is a key factor in neuroinflammation. It is widely elevated in several cell types after stroke. The increased EMMPRIN appears to regulate the expression of matrix metalloproteinases (MMPs) and exacerbate the pathology of stroke-induced blood-brain barrier dysfunction, microvascular thrombosis and neuroinflammation. In light of the neurological effects of EMMPRIN, we present in this review the complex network of roles that EMMPRIN has in brain ischemia and ICH. We first introduce the structural features and biological roles of EMMPRIN, followed by a description of the increased expression of EMMPRIN in brain ischemia and ICH. Next, we discuss the pathophysiological roles of EMMPRIN in brain ischemia and ICH. In addition, we summarize several important treatments for stroke that target the EMMPRIN signaling pathway. Finally, we suggest that EMMPRIN may have prospects as a biomarker of stroke injury. Overall, this review collates experimental and clinical evidence of the role of EMMPRIN in stroke and provides insights into its pathological mechanisms.

The Exosome-Mediated PI3K/Akt/mTOR Signaling Pathway in Neurological Diseases

“…Stroke is considered the second leading cause of mortality and the third leading cause of disability worldwide with an increasing growth globally [ 68 , 69 ]. As a socioeconomic problem, stroke has a high morbidity and mortality rate [ 70 ]. Thus, it could decrease the life quality of patients and impose high economic costs on patients and healthcare systems [ 69 ].…”

“…There are three different types of stroke. Ischemic stroke and hemorrhagic stroke are the major types of strokes [ 69 , 70 ]. A transient ischemic attack (TIA) or mini-stroke is another type of stroke in which symptoms last less than 24 h and can be a warning sign for future strokes [ 68 ].…”

“…Ischemic stroke or brain ischemia is the most common type of stroke and occurs due to a blockage of blood flow to the brain. Obstruction is usually caused by blood clots and results in hypoxia, nutrient deprivation, and the induction of inflammation and oxidative stress [ 69 , 70 , 72 ]. Hemorrhagic stroke is caused by a blood vessel rupture, leading to intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH) [ 73 ].…”

“…The persistent bleeding from a hemorrhagic stroke causes oxidative stress, neuroinflammation, apoptosis, and BBB disruption [ 56 , 70 ]. In addition, the PI3K/Akt/mTOR pathway can modulate multiple cellular and molecular events including oxidative stress factors, inflammatory responses, programmed cell death, and cell survival, and it protects neurons and the brain from ischemic damages [ 9 , 74 , 75 ].…”

Neuroprotective effects of gemfibrozil in neurological disorders: Focus on inflammation and molecular mechanisms

“…6,7 Globally, cerebrovascular accident (CVA) burdens health systems with heavy morbidity and mortality and can be categorized into two types: ischemic and hemorrhagic. 8 Ischemic CVA, accounting for approximately 80% of all CVA cases, is a cerebrovascular pathology resulting from stenosis or occlusion of cerebral arteries, leading to disruption of cerebral blood flow and ischemic necrosis or encephalomalacia of specific brain tissue. 9 As a result of ischemia and hypoxia in brain tissues, the normal blood flow to neurons is disrupted in patients with ischemic CVA, leading to neuronal demise.…”