en Clinical Neuroscience Clinical Neuroscience Original Original <div style="text-align: justify;"><span style="font-size:14px;"><span style="font-family:Tahoma;"><span style="line-height:2;"><span style="color:black"><b>Objectives and aims: </b>Ischemic stroke, as one of the most common neurological conditions, has debilitating consequences both in mortality and morbidity for which there is only revascularization as a highly effective treatment; considering the mentioned fact, a great and varied effort has been shaped during the last decades to add neuroprotective agents for a better outcome; however, there are both knowledge and practical gaps. In this study, we aimed to evaluate the impact of Fingolimod as a neuroprotective agent by reducing necroptosis through immunomodulation on clinical outcomes in stroke patients, as an adjunct to standard care.&nbsp;&nbsp;</span><br> <span style="color:black"><b>Methods and Materials:</b> This clinical trial was conducted in 2021 and 2024 at Tehran Shariati Hospital. The study protocol received approval from the Institutional Review Board (IRB) of Tehran University of Medical Sciences under the ethical approval code <b>IR.TUMS.MEDICINE.REC.1398.5.99 </b>and<b> </b>registered in the Iranian registry of clinical trials <b>(IRCT20220423054619N1)</b>. The study sample included patients with ischemic stroke who presented to the ER within 4.5 hours after the onset of focal neurologic deficit and NIHSS of 6 or higher, which, in brain CT scan, there is no better explanation. We excluded strictly any patient with any block or old or new MI, due to Fingolimod complications. Patients were randomly assigned in a block of four to two classic and Fingolimod groups. In the first group, patients only received Alteplase (0.9 mg/kg). Based on the consensus of the literature, in the second group, Fingolimod was administered alongside Alteplase for three consecutive days (0.5 mg orally) which was adapted from the most common protocol used in previous studies, with particular reference to the study of zhu et al. mRS and NIHSS questionnaires were used before injection, 30 days, and 90 days after treatment. mRS and NIHSS scores were considered as primary outcomes of the study. Leukocyte major subtypes (CD4 and CD8) were also gathered in each group on day 1 and day 3. Data were analyzed with SPSS version 22.&nbsp; The incidence of strokes amenable to intervention and Fingolimod complications was analyzed between the two groups, with no significant difference. So, it is safe if a proper criterion is used.</span><br> <span style="color:black"><b>Results</b>: A total of 27 patients in the classic and 25 patients in the Fingolimod groups were evaluated. Baseline demographic. The mRS was initially comparable, but by days 30 and 90, a statistically significant difference emerged between the groups (p = 0.041 on day 30 and p = 0.030 on day 90). NIHSS was significantly improved in the Fingolimod group at day 90 post-stroke. (p= 0.026). A trend toward reduction was detected for leukocyte subtypes in the Fingolimod group on day 3, with a non-significant 26% reduction in CD4+ cells (p = 0.072) and a statistically significant 31% reduction in CD8+ cells (p = 0.008).</span><br> <span style="color:black"><b>Conclusion</b>: Fingolimod plus Alteplase may be associated with improved neurologic function in ischemic stroke patients compared to Alteplase alone. The combination was well-tolerated, with a safety profile comparable to Alteplase monotherapy. Further research is needed <strong><span style="font-weight:normal">before clinical implementation can be recommended</span></strong><b>.</b></span></span></span></span></div> Fingolimod, Stroke, Alteplase, Neuroprotective agents 0 0 http://bcn.iums.ac.ir/browse.php?a_code=A-10-8493-1&slc_lang=en&sid=1 Hamed Shahriyari Hamedshahriyari69@gmail.com 13700319475328460057394 13700319475328460057394 Yes Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran Siamak Abdi Siamak.abdi@yahoo.com 13700319475328460057395 13700319475328460057395 No Center for Orthopedic Trans-disciplinary Applied Research, Tehran University of Medical Sciences, Tehran, Iran Niayesh Mohebbi Niyayesh_mohebbi@yahoo.com 13700319475328460057396 13700319475328460057396 No Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Farzad Fatehi fatehifa@gmail.com 13700319475328460057397 13700319475328460057397 No Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran Elham Dirandeh dirandehelham@gmail.com 13700319475328460057398 13700319475328460057398 No Clinical Research Development Unit, Kowsar Educational, Research and Therapeutic Hospital, Semnan University of Medical Sciences, Semnan, Iran Sanaz Soleimani ssolymany1377@yahoo.com 13700319475328460057399 13700319475328460057399 No Lung Transplantation Research Center (LTRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran Askar Ghorbani as.ghorbani67@gmail.com 13700319475328460057400 13700319475328460057400 No Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran