ORIGINAL_SCIENTIFIC_ARTICLE Currently, despite decades of trial and error, peripheral nerve injury is an impenetrable clinical dilemma. Any proven effective pharmacologic agent leads to a decisive leap forward to the clinical management of neuropathies. This study investigated the effects of tacrolimus and erythropoietin on sciatic nerve regeneration. Twenty-three mice were randomly assigned to tacrolimus, erythropoietin, tacrolimus + erythropoietin, control, and sham groups following sciatic nerve crush via hemostatic forceps. Medications were administered for 28 consecutive days. The sham group received neither crush injury nor medication. Histopathologic, immunohistochemical, and walking track analyses were performed. In the erythropoietin group, axonal swelling was significantly reduced and the average axonal number significantly recovered up to 75% of normal nerve compared to other groups. Marked immunoreactivity to GFAP and S-100 protein was present in the tacrolimus group. Nevertheless, at least moderate GFAP and S-100 expressions were observed in all of the groups. Functional recovery was superior in the tacrolimus group after 14 days, although a complete return to near-normal function was achieved in all groups after 28 days, regardless of the medication used. Our data supported the neurotrophic effects of tacrolimus and erythropoietin; however, not enough data was gathered to confirm their synergistic effects. Whether these results are extensible to clinical scenarios requires further detailed investigations. https://macvetrev.mk/LoadArticlePdf/361 2023-6-30 147 163 https://doi.org/10.2478/macvetrev-2023-0020 crush injury erythropoietin regeneration sciatic nerve tacrolimus Kimia Mansouri false 1 Department of Clinical Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran AUTHOR Hamidreza Fattahian hamidrezafattahian@yahoo.com false 2 Department of Clinical Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran LEAD_AUTHOR Alireza Jahandideh false 3 Department of Clinical Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran AUTHOR Hesameddin Akbarein false 4 Department of Food Hygiene and Quality Control, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran AUTHOR Jones, S., Eisenberg, H.M., Jia, X. (2016). Advances and future applications of augmented peripheral nerve regeneration. 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