Brain Histology and Immunohistochemistry After Resuscitation From Hemorrhagic Shock in Swine With Pre-Existing Atherosclerosis and Sodium Thiosulfate (Na 2 S 2 O 3 ) Treatment

Frontiers in Medicine

article

Nicole Denoix¹  Oscar McCook²  Angelika Scheuerle³  Thomas Kapapa⁴  Andrea Hoffmann²  Harald Gündel¹  Christiane Waller⁵  Csaba Szabo⁶  Peter Radermacher²  Tamara Merz² 

[1]Clinic for Psychosomatic Medicine and Psychotherapy, Ulm University Medical Center

[2]Institute for Anesthesiological Pathophysiology and Process Engineering, Ulm University Medical Center

[3]Division of Neuropathology, Institute for Pathology, Ulm University Medical Center

[4]Clinic for Neurosurgery, Ulm University Medical Center

[5]Department of Psychosomatic Medicine and Psychotherapy, Nuremberg General Hospital, Paracelsus Medical University

[6]Department of Science and Medicine, University of Fribourg

关键词: hydrogen sulfide;    cystathionine-γ-lyase;    cystathionine-β-synthase;    oxytocin receptor;    hypoxia;    glial fibrillary acidic protein;    nitrotyrosine;    paraventricular nucleus;   

DOI  :  10.3389/fmed.2022.925433

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Background The hydrogen sulfide (H 2 S) and the oxytocin/oxytocin receptor (OT/OTR) systems interact in the central nervous and cardiovascular system. As a consequence of osmotic balance stress, H 2 S stimulates OT release from the paraventricular nuclei (PVN) in the hypothalamic regulation of blood volume and pressure. Hemorrhagic shock (HS) represents one of the most pronounced acute changes in blood volume, which, moreover, may cause at least transient brain tissue hypoxia. Atherosclerosis is associated with reduced vascular expression of the main endogenous H 2 S producing enzyme cystathionine-γ-lyase (CSE), and, hence, exogenous H 2 S administration could be beneficial in these patients, in particular after HS. However, so far cerebral effects of systemic H 2 S administration are poorly understood. Having previously shown lung-protective effects of therapeutic Na 2 S 2 O 3 administration in a clinically relevant, long-term, porcine model of HS and resuscitation we evaluated if these protective effects were extended to the brain. Methods In this study, available unanalyzed paraffin embedded brain sections (Na 2 S 2 O 3 N = 8 or vehicle N = 5) of our recently published HS study were analyzed via neuro-histopathology and immunohistochemistry for the endogenous H 2 S producing enzymes, OT, OTR, and markers for brain injury and oxidative stress (glial fibrillary acidic protein (GFAP) and nitrotyrosine). Results Neuro-histopathological analysis revealed uninjured brain tissue with minor white matter edema. Protein quantification in the hypothalamic PVN showed no significant inter-group differences between vehicle or Na 2 S 2 O 3 treatment. Conclusions The endogenous H 2 S enzymes, OT/OTR co-localized in magnocellular neurons in the hypothalamus, which may reflect their interaction in response to HS-induced hypovolemia. The preserved blood brain barrier (BBB) may have resulted in impermeability for Na 2 S 2 O 3 and no inter-group differences in the PVN. Nonetheless, our results do not preclude that Na 2 S 2 O 3 could have a therapeutic benefit in the brain in an injury that disrupts the BBB, e.g., traumatic brain injury (TBI) or acute subdural hematoma (ASDH).

【 授权许可】

CC BY