Effects of riociguat and momordica charantia on cerebral vasospasm following experimental subarachnoid hemorrhage in the rabbit

Background: Cerebral vasospasm is the most important complication that determines mortality and morbidity following subarachnoid hemorrhage. The effectiveness of vasospasm treatments is not yet at the desired level. Riociguat used in the treatment of pulmonary HT is a guanylate cyclase activator. By acting directly on guanylate cyclase (GC), it provides cGMP a conversion and acts by increasing the NO sensitivity of GC. NO provides relaxation of smooth muscle by reducing the amount of intracellular calcium. It has been shown in studies that the extracts of Momordica Charantia, commonly known as bitter pulp or bitter melon in the world, known as potency pomegranate in our country, have strong antioxidant and free radical scavenging activity. In our study, the drugs to be applied on vasospasm created by the experimental SAH model; It is aimed to determine the changes in the basilar artery diameter and to evaluate and investigate their possible neuroprotective effects in terms of morphological, histopathological and immunohistochemical. Materials and Methods: Male New Zealand white rabbits weighing 2.5-4 kg were used in this study. They were divided into 4 groups as control (n:7), SAH (n:7), Riociguat (n:7), M.Charantia (n:7) groups. Apart from the control group, other groups with SAH; In the riociguat group, 10 mg/kg Riociguat was administered perorally for 3 days (1x1/24 hour dose) following SAH. At the end of 72 hours, perfusion and fixation were performed and the cerebrum, cerebellum and brainstem were removed and taken for histopathological examination. Lumen area and wall thickness of the basilar artery, vessel wall structure and cerebral tissue were evaluated morphologically, histopathologically and immunohistochemically. Results: In histological and morphometric examination, visible contraction in the vascular structures of the animals in which SAH model was applied, intense erythrocyte accumulation around the basilar artery, narrowed arterial lumen and edema in the perivascular area were detected. In the riociguat group, basilar artery diameters were similar to the control group, effective vasodilation was achieved, erythrocyte accumulation was eliminated and their lumens were enlarged. In the Momordica Charantia group, effective dilatation of the basilar artery and hemorrhagic accumulation around the tissue and local erythrocyte aggregation were detected. In the histopathological examination, neuroglial cells, pycnotic changes in neuron nuclei and disruption of the blood-brain barrier were observed in the brain stem and cerebral tissue sections in the SAH group. It was determined that the general cell structures and nuclear structure of the riociguat experimental group was compatible with the control group. In the Momordica Charantia experimental group, some of the changes in the SAH group were observed and the general structure of the neural tissue was similar to the control group. Despite the irregularity of the cell structures and changes in the nuclear structures, the morphological structure was preserved. In contrast to the riociguat group, partial hemorrhagic infiltration was found in the neural tissue. Conclusion: Riociguat and M.Charantia, applied in vasospasm after SAH in rabbits, have been shown to be effective in preventing or reversing vasospasm caused by SAH with their vasodilator and anti-inflammatory effects, and provide neuroprotection in ischemia that develops after vasospasm and can be used in vasospasm treatment strategies. Keywords: Subarachnoid Hemorrhage, Vasospasm, Riociguat, Momordica Charantia