Veysel KIYAK, Mustafa Namık ÖZTANIR, Neşe Başak TÜRKMEN, Aslı TAŞDEMİR, Osman ÇİFTÇİ

Assessment of sertraline activity in a vasospasm model following experimental subarachnoid haemorrhage

Vasospasm following subarachnoid haemorrhage (SAH) is a process yet to be fully clarified in terms of its aetiology and results. According to one of the many theories about vasospasm developing after SAH, the process results from an increase of pro-inflammatory agents and decrease in antioxidant agents. Other hand experimental studies on rats found a significant decrease in the pro-inflammatory parameters TNF-α and IL-1β in the blood values obtained after the use of sertraline. In this study, the findings regarding the effectiveness of sertraline in the treatment of vasospasm developing an experimental SAH model are presented. In this study, adult males of Spraque-Dawley breed, not used in any previous study and weighing between 250–350 g, were used. Rats were divided into 4 groups with the control group (n=5) and other groups (n=6 in each). Group 1 was the control, and Group 3 was the sertraline group. In Groups 2 and 4, SAH was initiated by giving rats autologous arterial blood in the cisterna magna. The tissues were examined in terms of mononuclear cell infiltration, vascular congestion, and neuron degeneration. In the experimental SAH model based on these values, it was found that the use of sertraline significantly reduced mononuclear cell infiltration, vascular congestion, and neuron degeneration. Moreover, in animal studies, it was shown that SSRIs increased neurogenesis and release of neurotrophins from the hippocampus. In our study, it was concluded that sertraline was effective in dissolving vasospasm in the experimental SAH model. However, we further believe that more experimental studies to investigate other SSRI compounds of the same family can contribute to the knowledge and understanding of this process.

PDF

___

1. Yasargil MG, Fox JL. The microsurgical approach to intracranial aneurysms. Surg Neurol. 1975;3:7-14.

2. Kassell NF, Shaffrey ME, Shaffrey CL. Cerebral vasospasm following aneurysmal subarachnoid hemorrhage. In: Apuzzo MLJ, ed, Brain surgery: Complication avoidance and management. 1. New York: Churchill Livingstone, 1993;847-56.

3. Liu‐DeRyke X, Rhoney DH. Cerebral vasospasm after aneurysmal subarachnoid hemorrhage: An overview of pharmacologic management. Pharmacotherapy. 2006;26:182-203.

4. Göker B, Akçakaya MO, Hamamcıoğlu MK, et al. Serebral vazospazm: Klinik izlem ve tedavi [Cerebral vasospasm: Clinical monitoring and treatment]. Türk Nöroşir Derg. 2018;28:119-23.

5. Duan W, Peng Q, Masuda N, et al. Sertraline slows disease progression and increases neurogenesis in N171-82Q mouse model of Huntington's disease. Neurobiol Dis. 2008;30:312-22.

6. Kumar P, Kumar A. Possible neuroprotective effect of Withania somnifera root extract against 3-nitropropionic acid-induced behavioral, biochemical, and mitochondrial dysfunction in an animal model of Huntington's disease. J Med Food. 2009;12:591-600.

7. Hiemke C, Härtter S. Pharmacokinetics of selective serotonin reuptake inhibitors. Pharmacol Ther. 2000;85:11-28.

8. Huzarska M, Zieliński M, Herman ZS. Repeated treatment with antidepressants enhances dopamine D1 receptor gene expression in the rat brain. Eur J Pharmacol. 2006;532:208-13.

9. Gill JS, Jamwal S, Kumar P, et al. Sertraline and venlafaxine improves motor performance and neurobehavioral deficit in quinolinic acid induced Huntington’s like symptoms in rats: Possible neurotransmitters modulation. Pharmacol Rep. 2017;69:306-13.

10. 1Siepmann T, Penzlin AI, Kepplinger J, et al. Selective serotonin reuptake inhibitors to improve outcome in acute ischemic stroke: Possible mechanisms and clinical evidence. Brain Behav. 2015;5:e00373.

11. Young JB, Singh TD, Rabinstein AA, et al. SSRI/SNRI use is not associated with increased risk of delayed cerebral ischemia after aSAH. Neurocrit Care. 2016;24:197-201.

12. Shin TK, Kang MS, Lee HY, et al. Fluoxetine and sertraline attenuate postischemic brain injury in mice. Korean J Physiol Pharmacol. 2009;13:257- 63.

13. Richardson BP. Serotonin and nociception. Ann N Y Acad Sci. 1990;600:511-9.

14. Abd-Elsameea AA, Moustaf AA, Mohamed AM. Modulation of the oxidative stress by metformin in the cerebrum of rats exposed to global cerebral ischemia and ischemia/reperfusion. Eur Rev Med Pharmacol Sci. 2014;18:2387-92.

15. Kumar P, Kumar A. Possible role of sertraline against 3-nitropropionic acid induced behavioral, oxidative stress and mitochondrial dysfunctions in rat brain. Prog Neuropsychopharmacology Biol Psychiatry. 2009;33:100-8.