Effects of argon in the acute phase of subarachnoid hemorrhage in an endovascular perforation model in rats

Abstract

Objective: 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: 19 male Wistar rats were randomly assigned to 3 treatment groups. SAH was induced using the endovascular filament perforation model. Cerebral blood flow (CBF), mean arterial blood pressure (MAP) and body temperature were measured continuously. Group A received 2 hours of ventilation by 50% Argon/50% O2 (n=7) immediately following SAH. Group B underwent a sham operation, and was also ventilated by Argon/O2 (n=6). Group C received a SAH but no further treatment (n=6). Pre- and postoperatively neurological and behavioral testing was performed. Histology and immunohistochemistry were used to evaluate the extent of brain injury and vasospasm. Results: The CBF 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 to baseline (85.8±26.0mmHG) and normalized thereafter. MAP in both groups showed no significant differences (p=0.3123). Immunohistochemical staining for NeuN demonstrated a decrease of hippocampal immunoreactivity after SAH in the CA 1-3 region compared to baseline (p=0.0127). Animals in the argon ventilated group showed less neuronal loss compared to untreated SAH animals (p<0.0001). Iba-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 to untreated SAH animals (CA1: 5.48±2.39%; CA2: 4.85±4.06%; CA3: 4.22±3.01%; DG: 3.82±3.23%). Less microglia accumulation indicated less activation in the argon ventilated group (p=0.0007). The Neuroscore assessment revealed no treatment benefit after SAH compared to baseline (p=0.385). Conclusion: In the present study neuroprotective effects of argon occurred early after SAH. As neurological deterioration was similar in the pre- and absence of Argon, it remains uncertain if neuroprotective effects translate in improved outcome over time.