Increased perihematomal neuron autophagy and plasma thrombin–antithrombin levels in patients with intracerebral hemorrhage

Abstract

Animal studies have demonstrated that autophagy was involved in neuronal damage after intracerebral hemorrhage (ICH). Several studies showed thrombin–antithrombin (TAT) plasma levels were elevated in patients with ICH. In this study, we aimed to evaluate if autophagy occurred in patients with ICH; and the relationship between the severity of brain injury and plasma TAT levels.A novel tissue harvesting device was used during hematoma removal surgery to collect loose fragments of tissue surrounding the affected brain area in 27 ICH patients with hematoma volumes of >30 mL in the basal ganglia. Control tissues were obtained from patients who underwent surgery for arteriovenous malformation (n = 25). Transmission electron microscopy (TEM) and immunohistochemistry for autophagy-related proteins were used to evaluate the ultrastructural and morphologic cellular characteristics; and the extent of autophagy in the recovered tissue specimens. Stroke severity was assessed by using the Glasgow Coma Scale (GCS) and the National Institutes of Health Stroke Scale (NIHSS). An enzyme-linked immunosorbent assay (ELISA) was used to measure plasma TAT levels.Transmission electron microscopy showed autophagosomes and autolysosomes exist in neurons surrounding the hematoma, but not in the control tissues. The number of cells containing autophagic vacuoles correlated with the severity of brain injury. Immunohistochemistry showed strong LC3, beclin 1, and cathepsin D staining in ICH tissue specimens. Plasma TAT levels correlated positively with autophagic cells and ICH severity (P < .01).Autophagy was induced in perihematomal neurons after ICH. Autophagy and plasma TAT levels correlated positively with severity of brain injury. These results suggest that autophagy and increased plasma TAT levels may contribute to the secondary damage in ICH patients.

GOLGA2/GM130 is a novel target of neuroprotection therapy in intracerebral hemorrhage

“…Autophagy is a tightly regulated process for the bulk removal of degraded cytoplasmic macromolecules and organelles in mammalian cells via lysosomes, thus maintaining cell homeostasis [29]. A previous study demonstrated that the higher the level of autophagic neurons in patients with ICH, the greater the severity of neuronal dysfunction [30]. In our study, elevated LC3-II and decreased p62 in the ICH rat brain indicated excessive autophagy ux induced by brain injury.…”

Ibrutinib ameliorates cerebral ischemia/reperfusion injury through autophagy activation and PI3K/Akt/mTOR signaling pathway in diabetic mice

“…Stroke is a major cause of disability, and has been one of the most referenced causes of mortality worldwide. Ischemic stroke and hemorrhagic stroke accounted for approximately 80% and 20%, respectively, of stroke cases [ 1 ]. Thus, reducing brain injury and improving the prognosis of ischemic stroke is becoming an urgent neurology problem.…”

Inhibition of PTEN Ameliorates Secondary Hippocampal Injury and Cognitive Deficits after Intracerebral Hemorrhage: Involvement of AKT/FoxO3a/ATG‐Mediated Autophagy

“…Recently, accumulating evidences have shown that iron released from the hematoma contributes to autophagy activation after ICH [14][15][16], but it is unknown that this process induces a beneficial or detrimental effect. Most studies support the notion that ICH-induced autophagy exacerbated histological and neurobehavioral consequences [13,15,17]. In contrast, Duan et al found that activated autophagy exhibited neuroprotective effects against secondary brain injury via inhibiting endoplasmic reticulum stress at the early stage post-ICH [18].…”