Selective Ferroptosis Inhibitor Liproxstatin-1 Attenuates Neurological Deficits and Neuroinflammation After Subarachnoid Hemorrhage.

Ferroptosis is a form of iron-dependent regulated cell death. Evidence of its existence and the effects of its inhibitors on subarachnoid hemorrhage (SAH) is still lacking. In the present study, we found that liproxstatin-1 protected HT22 cells against hemin-induced injury by protecting mitochondrial functions and ameliorating lipid peroxidation. In in vivo experiments, we demonstrated the presence of characteristic shrunken mitochondria in ipsilateral cortical neurons after SAH. Moreover, liproxstatin-1 attenuated the neurological deficits and brain edema, reduced neuronal cell death, and restored the redox equilibrium after SAH. The inhibition of ferroptosis by liproxstatin-1 was associated with the preservation of glutathione peroxidase 4 and the downregulation of acyl-CoA synthetase long-chain family member 4 as well as cyclooxygenase 2. In addition, liproxstatin-1 decreased the activation of microglia and the release of IL-6, IL-1ß, and TNF-α. These data enhance our understanding of cell death after SAH and shed light on future preclinical studies.

Severe cerebral edema induced by watershed shift after bypass in a patient with chronic steno-occlusive disease: a case report and short literature review.

BACKGROUND: Carotid occlusive disease is a type of progressive disease resulting in ischemic stroke. Extracranial-intracranial bypass surgery represents a valid therapeutic option when medical treatment does not make effects. The appearance of cerebral edema following bypass is common during acute stage. Additionally, there are many causes of mild cerebral edema, such as hemodynamic changes, venous congestion and others. However, severe edema involving large brain tissue, which presents as reversible aphasia and hemiplegia, remains to be elucidated. CASE PRESENTATION: A 55-year-old man was admitted to the neurosurgery department for repeated dizziness for over a year and sudden onset of syncope 1 month prior, and he was diagnosed with carotid occlusive disease. After surgical contraindications were excluded, dual bypass and encephalo-duro-myo-synangiosis were performed. Although blood pressure and fluid management were strictly under control promptly after surgery, massive cerebral edema involving the left anterior cerebral artery and middle cerebral artery territories occurred from the 6th day after surgery. Additionally, no discernible cerebral infarction or hemorrhage occurred. Moreover, the cerebral blood flow of the middle cerebral artery displayed an early decrease followed by delayed elevation on the left side. Without restricting the spreading of cerebral edema, life-threatening cerebral herniation could develop at any time. Mannitol and furosemide were administered for impending cerebral herniation. The amelioration of symptoms was noticed on the 16th day after surgery. The patient felt relief on the 21st day after surgery. Digital subtraction angiography performed on the 180th day after surgery demonstrated the patency of dual anastomosed vessels, and the patient recovered without any permanent neurological deficit. CONCLUSION: Based on changes in cerebral blood flow and reversible symptoms, the "watershed shift" phenomenon could explain such a severe deficit. However, this deficit was not the same as the classical presentation of the "watershed shift", which involves a moderate amount of brain tissue and presents significant increases in cerebral blood flow. In addition to the "watershed shift", a swollen temporal muscle may also participate in the progression of focal edema.