Anti-DEspR antibody treatment improves survival and reduces neurologic deficits in a hypertensive, spontaneous intracerebral hemorrhage (hsICH) rat model

Progressive secondary brain injury—induced by dysregulated neuroinflammation in spontaneous intracerebral hemorrhage (sICH)—underlies high sICH-mortality and remains without FDA-approved pharmacotherapy. Clinical insight that hematoma-directed interventions do not improve mortality prioritizes resol...

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Bibliographic Details
Published in:Scientific reports 2023-02, Vol.13 (1), p.2703-14, Article 2703
Main Authors: Herrera, Victoria L. M., Gromisch, Christopher M., Decano, Julius L., Pasion, Khristine Amber, Tan, Glaiza L. A., Hua, Ning, Takahashi, Courtney E., Greer, David M., Ruiz-Opazo, Nelson
Format: Article
Language:English
Subjects:
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Animals
Apoptosis
Brain Injuries - complications
Brain injury
CD11b antigen
Cerebral Hemorrhage - complications
Cerebral Hemorrhage - drug therapy
Drug therapy
Endothelin 1
Endothelins
Female
Hematoma
Hemorrhage
Humanities and Social Sciences
Hypertension
Hypertension - complications
Inflammation
Leukocytes (neutrophilic)
Male
Monoclonal antibodies
Mortality
multidisciplinary
Neutrophils
Pseudogenes
Rats
Science
Science (multidisciplinary)
Stroke - complications
Traumatic brain injury
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Summary:Progressive secondary brain injury—induced by dysregulated neuroinflammation in spontaneous intracerebral hemorrhage (sICH)—underlies high sICH-mortality and remains without FDA-approved pharmacotherapy. Clinical insight that hematoma-directed interventions do not improve mortality prioritizes resolving acute secondary brain injury in sICH. As neutrophils are implicated in sICH secondary brain injury, we tested whether inhibition of a rogue neutrophil-subset expressing the dual endothelin-1/signal peptide receptor (DEspR) and associated with secondary tissue injury, DEspR+ CD11b+ immunotype, will attenuate mortality in a hypertensive-sICH (hsICH) rat model. We confirmed sICH-related deaths in hsICH-rats by T2*-weighted 9.4 T MRI and DEspR+ neutrophils in hsICH-rat brain perihematomal areas by immunostaining. At acute sICH, anti-DEspR muIgG1-antibody, mu10a3, treatment increased median survival in hsICH rats vs controls (p 
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-28149-3