Effects of Argon in the Acute Phase of Subarachnoid Hemorrhage in an Endovascular Perforation Model in Rats

Abstract

Abstract Background Subarachnoid hemorrhage (SAH) is a devastating disease with high morbidity and mortality. Neuroprotective effects of the noble gas argon have been shown in animal models of ischemia. The aim of this study was to investigate the effects of argon in the immediate early phase of SAH in a rat model. Methods A total of 19 male Wistar rats were randomly assigned to three treatment groups. SAH was induced using a endovascular filament perforation model. Cerebral blood flow, mean arterial blood pressure (MAP), and body temperature were measured continuously. Group A received 2 h of ventilation by 50% argon/50% O2 (n = 7) immediately following SAH. Group B underwent a sham operation and was also ventilated by 50% argon/50% O2 (n = 6). Group C underwent SAH and 50% O2/50% N2 ventilation (n = 6). Preoperative and postoperative neurological and behavioral testing were performed. Histology and immunohistochemistry were used to evaluate the extent of brain injury and vasospasm. Results The cerebral blood flow dropped in both treatment groups after SAH induction (SAH, 63.0 ± 11.6% of baseline; SAH + argon, 80.2 ± 8.2% of baseline). During SAH, MAP increased (135.2 ± 10.5%) compared with baseline values (85.8 ± 26.0 mm Hg) and normalized thereafter. MAP in both groups showed no significant differences (p = 0.3123). Immunohistochemical staining for neuronal nuclear antigen demonstrated a decrease of hippocampal immunoreactivity after SAH in the cornu ammonis region (CA) 1–3 compared with baseline hippocampal immunoreactivity (p = 0.0127). Animals in the argon-ventilated group showed less neuronal loss compared with untreated SAH animals (p < 0.0001). Ionized calcium-binding adaptor molecule 1 staining showed a decreased accumulation after SAH + argon (CA1, 2.57 ± 2.35%; CA2, 1.89 ± 1.89%; CA3, 2.19 ± 1.99%; DG, 2.6 ± 2.24%) compared with untreated SAH animals (CA1, 5.48 ± 2.39%; CA2, 4.85 ± 4.06%; CA3, 4.22 ± 3.01%; dentate gyrus (DG), 3.82 ± 3.23%; p = 0.0007). The neuroscore assessment revealed no treatment benefit after SAH compared with baseline (p = 0.385). Conclusion In the present study, neuroprotective effects of argon occurred early after SAH. Because neurological deterioration was similar in the preadministration and absence of argon, it remains uncertain if neuroprotective effects translate in improved outcome over time.