Brain Histology and Immunohistochemistry After Resuscitation From Hemorrhagic Shock in Swine With Pre-Existing Atherosclerosis and Sodium Thiosulfate (Na2S2O3) Treatment

Abstract

BackgroundThe hydrogen sulfide (H2S) and the oxytocin/oxytocin receptor (OT/OTR) systems interact in the central nervous and cardiovascular system. As a consequence of osmotic balance stress, H2S 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 H2S producing enzyme cystathionine-γ-lyase (CSE), and, hence, exogenous H2S administration could be beneficial in these patients, in particular after HS. However, so far cerebral effects of systemic H2S administration are poorly understood. Having previously shown lung-protective effects of therapeutic Na2S2O3 administration in a clinically relevant, long-term, porcine model of HS and resuscitation we evaluated if these protective effects were extended to the brain.MethodsIn this study, available unanalyzed paraffin embedded brain sections (Na2S2O3N = 8 or vehicle N = 5) of our recently published HS study were analyzed via neuro-histopathology and immunohistochemistry for the endogenous H2S producing enzymes, OT, OTR, and markers for brain injury and oxidative stress (glial fibrillary acidic protein (GFAP) and nitrotyrosine).ResultsNeuro-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 Na2S2O3 treatment.ConclusionsThe endogenous H2S 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 Na2S2O3 and no inter-group differences in the PVN. Nonetheless, our results do not preclude that Na2S2O3 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).

The Effect of Targeted Hyperoxemia on Brain Immunohistochemistry after Long-Term, Resuscitated Porcine Acute Subdural Hematoma and Hemorrhagic Shock

“…In our study, the presence of albumin extravasation served as an indication of the destruction of the blood-brain barrier, which is consistent with findings from a previous study conducted on gerbils, wherein immunohistochemical analysis demonstrated increased permeability of the blood-brain barrier to serum albumin after infarction in the hippocampus [13]. In comparison to our prior investigations in swine, the following disparities were observed: following HS alone without simultaneous ASDH or any other direct acute brain injury, no alterations in the levels of extravascular albumin had been noted [14], whereas following ASDH alone, i.e., direct acute brain injury, but without concomitant circulatory depression, a significant increase in extravascular albumin was detected in the ipsilateral, i.e., blood-injected brain hemisphere [6]. In the present study, the concurrent occurrence of ASDH and HS induced an extravasation of albumin.…”

“…The present study revealed only a little nitrotyrosine expression, regardless of the blood-injected vs. instrumented-only hemisphere. In comparison, in the previously mentioned study focusing on HS alone, no expression of nitrotyrosine was detected [ 14 ]. Conversely, following ASDH alone, a significantly higher level of nitrotyrosine could be observed in the ipsilateral hemisphere [ 6 ].…”