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Noman Ullah Wazir
Zilli Huma
Irum Javaid
Farooq Khan
Amir Zaman Khan
Rabia Syed


Pirfenidone, Aneurysm Clip Model, Spinal Cord Compression Injury, neuronal degeneration, MAP2.


Aim: To explore the neuroprotective effect of pirfenidone in rat’s aneurysm clip compression spinal cord injury.

Methodology: A total of 30 healthy Sprague Dawley rats were randomly divided into spinal cord injury groups A, B and C. Group A received a placebo (n = 10), group B received 200 mg/kg/day of pirfenidone (n = 10) and group C received 500 mg/kg/day of pirfenidone. Based on the experimental duration of 14 and 28 days, each group was subdivided into groups 1 & 2 (n = 5 in each subgroup). An aneurysm clip with 70 g closing force was applied to the T7 level of the spinal cord for 1 minute to induce compression spinal cord injury. Immunohistochemistry by MAP2 anti-body for estimating viable neurons was performed.

Results: There were no normal viable neuronal cell bodies in the spinal cord injured areas in any groups. Nevertheless, neuronal cell body residues were detected in the injury sites and a statistically significant difference was witnessed within groups and between groups. The higher dose of 500 mg/kg/day of pirfenidone for 14 days slows down the process of neuronal degeneration in injury lesions compared to 200 mg/kg/day for a prolonged duration of 28 days.

Conclusion: Pirfenidone has no protective effect on neurons after spinal cord injury but due to its anti-oxidant and anti-inflammatory properties, it alters and delays the neurodegenerative process. This leads us to the future experimentation of pirfenidone in neurodegenerative diseases.

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1) Abu-Baker, N. N., Al-Zyoud, N. m. H., & Alshraifeen, A. (2021). Quality of life and self-care ability among individuals with spinal cord injury. Clinical Nursing Research, 30(6), 883-891.
2) Bozkurt, I., Ozturk, Y., Guney, G., Arslan, B., Gulbahar, O., Guvenc, Y., Senturk, S., & Yaman, M. E. (2022). Effects of pirfenidone on experimental head injury in rats. International Journal of Clinical and Experimental Pathology, 15(1), 20.
3) Braim, A. E. P., MacDonald, M. H., Bruss, M. L., Grattendick, K. J., Giri, S. N., & Margolin, S. B. (2009). Effects of intravenous administration of pirfenidone on horses with experimentally induced endotoxemia. American journal of veterinary research, 70(8), 1031-1042.
4) Cain, W., Stuart, R., Lefkowitz, D., Starnes, J., Margolin, S., & Lefkowitz, S. (1998). Inhibition of tumor necrosis factor and subsequent endotoxin shock by pirfenidone. International journal of immunopharmacology, 20(12), 685-695.
5) Castro-Torres, R. D., Chaparro-Huerta, V., Flores-Soto, M. E., Bañuelos-Pineda, J., Camins, A., Orozco-Suárez, S. A., Armendáriz-Borunda, J., & Beas-Zárate, C. (2014). A single dose of pirfenidone attenuates neuronal loss and reduces lipid peroxidation after kainic acid-induced excitotoxicity in the pubescent rat hippocampus. Journal of Molecular Neuroscience, 52(2), 193-201.
6) Chen, K., Deng, S., Lu, H., Zheng, Y., Yang, G., Kim, D., Cao, Q., & Wu, J. Q. (2013). RNA-seq characterization of spinal cord injury transcriptome in acute/subacute phases: a resource for understanding the pathology at the systems level. PloS one, 8(8), e72567.
7) Conforti, L., Gilley, J., & Coleman, M. P. (2014). Wallerian degeneration: an emerging axon death pathway linking injury and disease. Nature Reviews Neuroscience, 15(6), 394-409.
8) Forgione, N., & Fehlings, M. G. (2013). Novel insights into pathophysiology and emerging therapeutic opportunities. In. Future Medicine.
9) Guidlines, A. (2020). AVMA Guidelines for the Euthanasia of Animals. Retrieved 26 November 2022 from
10) Hale, M. L., Margolin, S. B., Krakauer, T., Roy, C. J., & Stiles, B. G. (2002). Pirfenidone blocks the in vitro and in vivo effects of staphylococcal enterotoxin B. Infection and immunity, 70(6), 2989-2994.
11) Hofman, F. (2002). Immunohistochemistry. Current protocols in immunology, 49(1), 21.24. 21-21.24. 23.
12) Kim, S.-W., Roh, J., & Park, C.-S. (2016). Immunohistochemistry for pathologists: protocols, pitfalls, and tips. Journal of pathology and translational medicine, 50(6), 411-418.
13) Kong, X., & Gao, J. (2017). Macrophage polarization: a key event in the secondary phase of acute spinal cord injury. Journal of cellular and molecular medicine, 21(5), 941-954.
14) Macías-Barragán, J., Sandoval-Rodríguez, A., Navarro-Partida, J., & Armendáriz-Borunda, J. (2010). The multifaceted role of pirfenidone and its novel targets. Fibrogenesis & tissue repair, 3(1), 1-11.
15) Margaritopoulos, G. A., Vasarmidi, E., & Antoniou, K. M. (2016). Pirfenidone in the treatment of idiopathic pulmonary fibrosis: an evidence-based review of its place in therapy. Core Evidence, 11, 11.
16) Rowland, J. W., Hawryluk, G. W., Kwon, B., & Fehlings, M. G. (2008). Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon. Neurosurgical focus, 25(5), E2.
17) S. Kim Suvarna, C. L., John D. Bancroft. (2019). Bancroft’s THEORY and PRACTICE of HISTOLOGICAL TECHNIQUES (eighth edition ed., Vol. ). Elsevier Limited.
18) Schaefer, C., Ruhrmund, D., Pan, L., Seiwert, S., & Kossen, K. (2011). Antifibrotic activities of pirfenidone in animal models. European Respiratory Review, 20(120), 85-97.
19) Seifirad, S. (2020). Pirfenidone: A novel hypothetical treatment for COVID-19. Medical hypotheses, 144, 110005.
20) Shi, Q., Liu, X., Bai, Y., Cui, C., Li, J., Li, Y., Hu, S., & Wei, Y. (2011). In vitro effects of pirfenidone on cardiac fibroblasts: proliferation, myofibroblast differentiation, migration and cytokine secretion. PloS one, 6(11), e28134.
21) Soderblom, C., Luo, X., Blumenthal, E., Bray, E., Lyapichev, K., Ramos, J., Krishnan, V., Lai-Hsu, C., Park, K. K., & Tsoulfas, P. (2013). Perivascular fibroblasts form the fibrotic scar after contusive spinal cord injury. Journal of Neuroscience, 33(34), 13882-13887.
22) Support, B. R. (2021). Euthanasia of Rodents. BU IACUC. Retrieved 26 November 2022 from
23) Vogelaar, C. F., König, B., Krafft, S., Estrada, V., Brazda, N., Ziegler, B., Faissner, A., & Müller, H. W. (2015). Pharmacological suppression of CNS scarring by deferoxamine reduces lesion volume and increases regeneration in an in vitro model for astroglial-fibrotic scarring and in rat spinal cord injury in vivo. PloS one, 10(7), e0134371.