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

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).