Tocilizumab Reduces Vasospasms, Neuronal Cell Death, and Microclot Formation in a Rabbit Model of Subarachnoid Hemorrhage.

Croci, Davide M; Wanderer, Stefan; Strange, Fabio; Grüter, Basil E; Sivanrupan, Sivani; Andereggen, Lukas; Casoni, Daniela; von Gunten, Michael; Widmer, Hans Rudolf; Di Santo, Stefano; Fandino, Javier; Mariani, Luigi; Marbacher, Serge (2021). Tocilizumab Reduces Vasospasms, Neuronal Cell Death, and Microclot Formation in a Rabbit Model of Subarachnoid Hemorrhage. (In Press). Translational stroke research Springer 10.1007/s12975-020-00880-3

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Early brain injury (EBI), delayed cerebral vasospasm (DCVS), and delayed cerebral ischemia (DCI) are common complications of subarachnoid hemorrhage (SAH). Inflammatory processes in the cerebrospinal fluid (CSF) are one of the causes for such complications. Our aim to study the effects of an IL-6 receptor antagonist (Tocilizumab) examines the occurrence of DCVS, neuronal cell death, and microclot formation in an acute SAH rabbit model. Twenty-nine New Zealand white rabbits were randomized into one of three groups as the SAH, SAH + Tocilizumab, and sham groups. In SAH groups, hemorrhage was induced by extracranial-intracranial arterial blood shunting from the subclavian artery into the cisterna magna under intracranial pressure (ICP) monitoring. In the second group, Tocilizumab was given once intravenously 1 h after SAH induction. Digital subtraction angiography was performed, and CSF and blood were sampled before and after (day 3) SAH induction. IL-6 plasma and CSF levels were measured. TUNEL, FJB, NeuN, and caspase-3 immunostaining were used to assess cell apoptosis, neurodegeneration, and neuronal cell death, respectively. Microclot formation was detected by fibrinogen immunostaining. Between baseline and follow-up, there was a significant reduction of angiographic DCVS (p < 0.0001) in the Tocilizumab compared with the SAH group. Tocilizumab treatment resulted in decreased neuronal cell death in the hippocampus (p = 0.006), basal cortex (p = 0.001), and decreased microclot formation (p = 0.02). Tocilizumab reduced DCVS, neuronal cell death, and microclot formation in a rabbit SAH model, and could be a potential treatment to prevent DCVS and DCI in SAH patients.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Neurochirurgie
04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurosurgery

UniBE Contributor:

Andereggen, Lukas; Casoni, Daniela; Widmer, Hans Rudolf and Di Santo, Stefano

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1868-4483

Publisher:

Springer

Language:

English

Submitter:

Nicole Söll

Date Deposited:

07 Jun 2021 15:38

Last Modified:

07 Jun 2021 15:46

Publisher DOI:

10.1007/s12975-020-00880-3

PubMed ID:

33409731

Uncontrolled Keywords:

Inflammation Interleukin-6 Neuronal cell death Subarachnoid hemorrhage Tocilizumab Vasospasm

BORIS DOI:

10.48350/155920

URI:

https://boris.unibe.ch/id/eprint/155920

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