Necrosulfonamide Alleviates Acute Brain Injury of Intracerebral Hemorrhage via Inhibiting Inflammation and Necroptosis

Xiangyu Zhang; Yan Zhang; Fei Wang; Yang Liu; V Wee Yong; Mengzhou Xue

doi:10.3389/fnmol.2022.916249

Necrosulfonamide Alleviates Acute Brain Injury of Intracerebral Hemorrhage via Inhibiting Inflammation and Necroptosis

Front Mol Neurosci. 2022 Jun 2:15:916249. doi: 10.3389/fnmol.2022.916249. eCollection 2022.

Authors

Xiangyu Zhang^{1

2}, Yan Zhang^{1

2}, Fei Wang^{1

2}, Yang Liu^{1

2}, V Wee Yong³, Mengzhou Xue^{1

2}

Affiliations

¹ Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
² Academy of Medical Science, Zhengzhou University, Zhengzhou, China.
³ Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.

Abstract

Objective: Intracerebral hemorrhage (ICH) is the most lethal subtype of stroke, without effective treatment. Necrosulfonamide (NSA), a specific inhibitor for mixed lineage kinase domain-like protein, has been reported to exert neuroprotective effects in neurological diseases by ameliorating neuroinflammation and necroptosis. We hypothesized that NSA would alleviate acute brain injury and improve behavioral outcomes after ICH.

Materials and methods: Male adult C57BL/6 mice were assigned randomly into three groups. In vehicle and treatment groups, animals were injected with collagenase VII to induce ICH. The solvent (0.25% DMSO) and NSA (5 mg/kg) were administrated intraperitoneally twice a day, respectively. The sham group was injected with saline and administrated with DMSO. The brain hematoma volume, inflammatory factors, and blood-brain barrier permeability were measured on day 3 after the operation. Fluorescent double immunostaining was performed to evaluate the neuronal death. Neurological functions were assessed.

Results: In the NSA group, the hematoma size was significantly reduced, inflammatory cells and cytokines were suppressed, and the blood-brain barrier was protected compared to vehicle controls. NSA dramatically reduced the death of neurons and improved the performance of neurological functions after ICH.

Conclusion: Necrosulfonamide has a neuroprotective role in alleviating acute brain injury in a mouse ICH model, and this is associated with reduced neuroinflammation and necroptosis.

Keywords: blood-brain barrier; intracerebral hemorrhage; mixed lineage kinase domain-like protein; necroptosis; necrosulfonamide; neuroinflammation.