1. Anti-inflammatory effect of meloxicam on experimental vasospasm in rat femoral artery Tayfun Hakan, M. Zafer Berkman, Turgay Ersoy, Ismail Karatas, Tangul San*, Serap Arbak* Department of Neurosurgery, Haydarpasa Numune Teaching and Research Hospital, Department of Histology and Embryology*, Marmara University, School of Medicine, Istanbul, Turkey Cerebral vasospasm greatly influences morbidity and mortality in patients following subarachnoidal haemorrhage (SAH). Inflammation is believed to play a role in post-haemorrhagic cerebral vasospasm. Meloxicam is a non-steroidal anti-inflammatory drug that preferentially inhibits cyclooxygenase (COX), which plays an important role in the biosynthesis of prostoglandins. In this study, we investigated the effect of meloxicam on rat femoral artery vasospasm using the radial wall thickness and cross-sectional lumen area as parameters under light, scanning and transmission electron microscopy examinations. A femoral artery vasospasm model in rats previously described by Okada et al was used. Spraque- Dawley rats (n=24) were randomly separated into three groups: a control group (n=8), an SAH group (n=8) and an SAH+meloxicam group (n=8). Rats in the treatment group (SAH+meloxicam) were given meloxicam at 2 mg/kg daily for 7 days. All animals were sacrificed 1 week later. After perfusion fixation, 10-mm segments of femoral arteries were removed and prepared for examination by light microscopy and scanning and transmission electron microscopy, and for morphometric analysis. A statistically significant difference (p<0.001) was detected in scanning, electron and light microscopic findings and morphometric analysis between the SAH and SAH+meloxicam groups. There were no significant differences between the control and SAH+meloxicam groups. Meloxicam treatment before vasospasm reduces ultrastructural and morphometric vasospastic changes in the femoral arteries of the rats. These findings strongly support the hypothesis that inflammation may play a role in one of the pathophysiologyical pathways of post-haemorrhagic cerebral vasospasm. After clinical trials, this agent could be used in treatment protocols for vasospasm following SAH.

2. Fig. 1: Microphotographs of the femoral arteries under a light microscope. (A) Control group: the endothelium is uniform and regular, the internal elastic lamina is non- convoluted and the smooth muscle cells are oriented concentrically (H&E, 400  ). (B) SAH group: there are degenerative changes in the endothelium and corrugation of the elastic lamina with increased wall thickness (H&E, 400  ). (C) SAH+meloxicam group: the endothelium is nearly as uniform and regular as for the control group. There is no convolution of the internal elastic lamina or increase in wall thickness (H&E, 400  ).

3. Fig. 2: Microphotographs of the femoral arteries under a transmission electron microscope. (A) Control group: the endothelium (E) is thin and regular, there is no convolution of the internal elastic lamina (IEL) or smooth muscle (M). (B) SAH group: the endothelium (E) is vacuolated and thick with a convoluted internal elastic lamina (IEL), and there is vacuole degeneration of smooth muscle (M). (C) SAH+meloxicam group: the endothelium (E), internal elastic lamina (IEL) and smooth muscle (M) are all nearly normal in appearance, with only small vacuole changes.

4. Fig. 3: Microphotographs of the femoral arteries under a scanning electron microscope. (A) Control group: the endothelium uniformly and regularly covers the surface of the lumen along the longitudinal axis. (B) SAH group: marked endothelial convolutions and an increase in wall thickness. (C) SAH+meloxicam group: endothelial convolutions are minimal.