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Effects of different platelet-rich plasma administration methods on peripheral nerve regeneration: A histomorphometric study

Year 2024, Volume: 41 Issue: 3, 557 - 562, 30.09.2024

Abstract

Peripheral nerve damage is a common medical problem that frequently leads to significant functional limitations and long-term disabilities. Platelet-rich plasma (PRP), a growth factor-rich substance, promotes axonal regeneration in peripheral nerve injuries. This study aimed to investigate the effect of PRP on axonal regeneration in Wistar rats (Rattus norvegicus) after peripheral nerve injury via histomorphometric analysis. This study used a post-test-only control-group design. Twenty-five white rats were randomly assigned to the control or treatment groups (n=5). The control group consisted of the sham-operated and saline groups. The treatment groups consisted of local, intraperitoneal, or combined PRP. A single dose of PRP was administered after axonotmesis of the sciatic nerve. After 21 days, a surgical procedure was performed to extract sciatic nerve tissue, which was then stained with Luxol fast blue for histomorphometric analysis. The mean diameter of the fibers, diameter of the axons, number of axons, and myelin sheath thickness were analyzed using MANOVA (p<0.05). Compared with the saline group, the PRP treatment group presented a greater number of regenerating myelinated axons with larger fiber and axon diameters, and thicker myelin (p<0.05). The myelinated axons in the sham-operated group showed a typical morphology, whereas those in the saline group showed a decrease in myelinated axons, smaller fiber and axon diameters, and thinner, irregular myelin sheaths. Injection of a combination of PRP, both intraperitoneally and locally, promoted the regeneration of damaged nerves in rats.

Ethical Statement

All experimental procedures were approved by the Research Ethics Committee of the Faculty of Veterinary Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia (Ref. no: 168/KEPH/IX/2022, September 14 2022).

Thanks

The authors thank all staff researchers for their support.

References

  • Zuo KJ, Gordon T, Chan KM, Borschel GH. Electrical stimulation to enhance peripheral nerve regeneration: Update in molecular investigations and clinical translation. Exp Neurol. 2020;332:113397.
  • Mukhtar NB, Umar YI, Mayana KI, Sumaila FG. Prevalence and pattern of peripheral nerve injuries in Kano Metropolis, Nigeria. AJPARS. 2017;9(1–2):22–6.
  • Kuffler DP, Foy C. Restoration of Neurological Function Following Peripheral Nerve Trauma. Vol. 21, International journal of molecular sciences. NLM (Medline); 2020.
  • Bekelis K, Missios S, Spinner RJ. Falls and peripheral nerve injuries: An age-dependent relationship. J Neurosurg. 2015 Nov 1;123(5):1223–9.
  • Li NY, Onor GI, Lemme NJ, Gil JA. Epidemiology of peripheral nerve injuries in sports, exercise, and recreation in the United States, 2009–2018. Phys Sportsmed. 2021;49(3):355–62.
  • Poetera CY, Abimanyu D. Peripheral nerve injury and its regeneration processes: a biomolecular point of view. BMJ. 2021;10(2):927–34.
  • Nagappan PG, Chen H, Wang DY. Neuroregeneration and plasticity: a review of the physiological mechanisms for achieving functional recovery postinjury. Mil Med Res. 2020;7:1–16.
  • Holmes SA, Barakat N, Bhasin M, Lopez NI, Lebel A, Zurakowski D, et al. Biological and behavioral markers of pain following nerve injury in humans. Neurobiology of Pain. 2020;7:100038.
  • Sánchez M, Garate A, Miren Bilbao A, Oraa J, Yangüela F, Sánchez P, et al. Platelet-Rich Plasma for Injured Peripheral Nerves: Biological Repair Process and Clinical Application Guidelines. In: Demystifying Polyneuropathy - Recent Advances and New Directions. IntechOpen; 2019.
  • Bastami F, Vares P, Khojasteh A. Healing effects of platelet-rich plasma on peripheral nerve injuries. Journal of Craniofacial Surgery. 2017;28(1):e49–57.
  • de Castro MV, Silva MVR da, Chiarotto GB, Volpe BB, Santana MH, Malheiros Luzo ÂC, et al. Reflex arc recovery after spinal cord dorsal root repair with platelet rich plasma (PRP). Brain Res Bull. 2019;152:212–24.
  • Yu W, Wang J, Yin J. Platelet-rich plasma: A promising product for treatment of peripheral nerve regeneration after nerve injury. Vol. 121, International Journal of Neuroscience. 2011. p. 176–80.
  • Wang S, Liu X, Wang Y. Evaluation of platelet-rich plasma therapy for peripheral nerve regeneration: a critical review of literature. Front Bioeng Biotechnol. 2022;10:808248.
  • Afsar SI, Yemisci OU, Cetin N. The role of platelet-rich plasma in peripheral nerve injuries. J Clin Anal Med. 2015;6:905–8.
  • Firat C, Aytekin AH, Durak MA, Geyik Y, Erbatur S, Dogan M, et al. Comparison of the effects of PRP and hyaluronic acid in promoting peripheral nerve regeneration. Ann Ital Chir. 2016;87(4):362–74.
  • Zhang W, Li C, Yang S, Xu C, Wang W, Nyengaard JR, et al. A stereological method for estimating the total length and size of myelinated fibers in rat cerebral cortex. J Neurosci Methods. 2008;172(1):21–6.
  • Arindra PK, Rahmat M, Rahardjo R. Regenerasi Nervus Mentalis akibat Cedera Penjepitan setelah Aplikasi Kombinasi Platelet Rich Plasma yang Diaktivasi Spons Kolagen dan Cytidine 5’-Diphosphocholine. J Ked Gi. 2016;7(2):138–44.
  • Ikumi A, Hara Y, Yoshioka T, Kanamori A, Yamazaki M. Effect of local administration of platelet-rich plasma (PRP) on peripheral nerve regeneration: An experimental study in the rabbit model. Microsurgery. 2018;38(3):300–9.
  • Zavala A, Martinez PC, Gutierrez GG, Vara MD, Pawlikowski W De. The Combined Use of Curcumin and Platelet-Rich Plasma Enhances Axonal Regeneration in Acute Nerve Injuries: An Experimental Study in a Rat Model. J Hand Microsurg. 2023;15(1):31–6.
  • Pandunugrahadi M, Irianto KA, Sindrawati O. The Optimal Timing of Platelet-Rich Plasma (PRP) Injection for Nerve Lesion Recovery: A Preliminary Study. Int J Biomater. 2022;2022:1–7.
  • Wu CC, Wu YN, Ho HO, Chen KC, Sheu MT, Chiang HS. The neuroprotective effect of platelet-rich plasma on erectile function in bilateral cavernous nerve injury rat model. J Sex Med. 2012;9(11):2838–48.
  • Cámara-Lemarroy CR, Guzmán-de la Garza FJ, Barrera-Oranday EA, Cabello-García AJ, García-Tamez A, Fernández-Garza NE. Celecoxib accelerates functional recovery after sciatic nerve crush in the rat. J Brachial Plex Peripher Nerve Inj. 2008;3(01):e128–31.
  • Emril DR, Wibowo S, Meliala L, Susilowati R. Cytidine 5′-diphosphocholine administration prevents peripheral neuropathic pain after sciatic nerve crush injury in rats. J Pain Res. 2016;287–91.
  • Jaggi AS, Jain V, Singh N. Animal models of neuropathic pain. Vol. 25, Fundamental and Clinical Pharmacology. 2011. p. 1–28.
  • Emril D, Hajar S, Ismy J. Efikasi platelet rich plasma (PRP) terhadap optimalisasi pengobatan nyeri neuropatik dan perbaikan fungsi neurologi paska cedera saraf. Banda Aceh; 2021.
  • Muttaqien A. Peran Platelet Rich Plasma Terhadap Perbaikan Fungsi Motorik Pada Tikus Putih (Rattus Novergicus) Pasca Cedera Saraf Tepi. [Banda Aceh]: Faculty of Medicine, Syiah Kuala University; 2022.
  • Wu YN, Liao CH, Chen KC, Chiang HS. Dual effect of chitosan activated platelet rich plasma (cPRP) improved erectile function after cavernous nerve injury. J Formos Med Assoc. 2022;121(1):14–24.
  • Kokkalas N, Kokotis P, Diamantopoulou K, Galanos A, Lelovas P, Papachristou DJ, et al. Platelet-rich plasma and mesenchymal stem cells local infiltration promote functional recovery and histological repair of experimentally transected sciatic nerves in rats. Cureus. 2020;12(5).
  • García de Cortázar U, Padilla S, Lobato E, Delgado D, Sánchez M. Intraneural platelet-rich plasma injections for the treatment of radial nerve section: A case report. J Clin Med. 2018;7(2):13.
  • Karakaş DÖ, Dandin Ö, Müftüoğlu T, Tihan D, Bal AS, Yıldırım Ş. Effect of platelet-rich plasma on postoperative peritoneal inflammation and adhesions. Arch Med Sci. 2021;17(5):1408.
  • Fox IK, Brenner MJ, Johnson PJ, Hunter DA, MacKinnon SE. Axonal regeneration and motor neuron survival after microsurgical nerve reconstruction. Microsurgery. 2012;32(7):552–62.
  • Emril D, Hajar S, Ismy J, Muttaqien A, Maulina M. The Efficacy of Platelet Rich Plasma on Optimalization of Neurologic Function Improvement After Nerve Injury. In: The 14th Biennial Convention of The ASEAN Neurological Association. Bangkok: Neurological Society of Thailand; 2021.
  • Wasterlain AS, Braun HJ, Dragoo JL. The Systemic Effects of Platelet-Rich Plasma. In: Maffulli N, editor. Platelet Rich Plasma in Musculoskeletal Practice. London: Springer London; 2016. p. 199–222.
  • Wasterlain AS, Braun HJ, Harris AHS, Kim HJ, Dragoo JL. The systemic effects of platelet-rich plasma injection. Am J Sports Med. 2013;41(1):186–93.
  • Knop E, De Paula LE, Fuller R. Platelet-rich plasma for osteoarthritis treatment. Vol. 56, Revista Brasileira de Reumatologia. Elsevier Editora Ltda; 2016. p. 152–64.
  • Winias S, Radithia D, Parmadiati AE, Soebadi B, Ernawati DS, Hadi P, et al. Allogenous Freeze-Dried Platelet-Rich Plasma Promotes Peripheral Myelin Repair in Chronic Constriction Nerve Injury. Syst Rev Pharm. 2020;11(6).
  • Sánchez M, Garate A, Delgado D, Padilla S. Platelet-rich plasma, an adjuvant biological therapy to assist peripheral nerve repair. Neural Regen Res. 2017;12(1):47–52.
  • Moegni K, Ekaputri K, Biben J, Rosadi I, Rosliana I, Sobariah S, et al. Evaluation of plasma PDGF and VEGF levels after systemic administration of activated autologous platelet-rich plasma. Biomedicine (Taipei). 2021;41:409–12.
  • Ikumi A, Hara Y, Okano E, Kohyama S, Arai N, Taniguchi Y, et al. Intraoperative Local Administration of Platelet-Rich Plasma (PRP) during Neurolysis Surgery for the Treatment of Digital Nerve Crush Injury. Case Rep Orthop. 2018;6:1–6.
  • Sánchez M, Anitua E, Delgado D, Sanchez P, Prado R, Orive G, et al. Platelet-rich plasma, a source of autologous growth factors and biomimetic scaffold for peripheral nerve regeneration. Vol. 17, Expert Opinion on Biological Therapy. Taylor and Francis Ltd; 2017. p. 197–212.
  • Rayilla RSR, Naidu MUR, Babu PP. Surgically Induced Demyelination in Rat Sciatic Nerve. Brain Sci. 2023;13(5).
Year 2024, Volume: 41 Issue: 3, 557 - 562, 30.09.2024

Abstract

References

  • Zuo KJ, Gordon T, Chan KM, Borschel GH. Electrical stimulation to enhance peripheral nerve regeneration: Update in molecular investigations and clinical translation. Exp Neurol. 2020;332:113397.
  • Mukhtar NB, Umar YI, Mayana KI, Sumaila FG. Prevalence and pattern of peripheral nerve injuries in Kano Metropolis, Nigeria. AJPARS. 2017;9(1–2):22–6.
  • Kuffler DP, Foy C. Restoration of Neurological Function Following Peripheral Nerve Trauma. Vol. 21, International journal of molecular sciences. NLM (Medline); 2020.
  • Bekelis K, Missios S, Spinner RJ. Falls and peripheral nerve injuries: An age-dependent relationship. J Neurosurg. 2015 Nov 1;123(5):1223–9.
  • Li NY, Onor GI, Lemme NJ, Gil JA. Epidemiology of peripheral nerve injuries in sports, exercise, and recreation in the United States, 2009–2018. Phys Sportsmed. 2021;49(3):355–62.
  • Poetera CY, Abimanyu D. Peripheral nerve injury and its regeneration processes: a biomolecular point of view. BMJ. 2021;10(2):927–34.
  • Nagappan PG, Chen H, Wang DY. Neuroregeneration and plasticity: a review of the physiological mechanisms for achieving functional recovery postinjury. Mil Med Res. 2020;7:1–16.
  • Holmes SA, Barakat N, Bhasin M, Lopez NI, Lebel A, Zurakowski D, et al. Biological and behavioral markers of pain following nerve injury in humans. Neurobiology of Pain. 2020;7:100038.
  • Sánchez M, Garate A, Miren Bilbao A, Oraa J, Yangüela F, Sánchez P, et al. Platelet-Rich Plasma for Injured Peripheral Nerves: Biological Repair Process and Clinical Application Guidelines. In: Demystifying Polyneuropathy - Recent Advances and New Directions. IntechOpen; 2019.
  • Bastami F, Vares P, Khojasteh A. Healing effects of platelet-rich plasma on peripheral nerve injuries. Journal of Craniofacial Surgery. 2017;28(1):e49–57.
  • de Castro MV, Silva MVR da, Chiarotto GB, Volpe BB, Santana MH, Malheiros Luzo ÂC, et al. Reflex arc recovery after spinal cord dorsal root repair with platelet rich plasma (PRP). Brain Res Bull. 2019;152:212–24.
  • Yu W, Wang J, Yin J. Platelet-rich plasma: A promising product for treatment of peripheral nerve regeneration after nerve injury. Vol. 121, International Journal of Neuroscience. 2011. p. 176–80.
  • Wang S, Liu X, Wang Y. Evaluation of platelet-rich plasma therapy for peripheral nerve regeneration: a critical review of literature. Front Bioeng Biotechnol. 2022;10:808248.
  • Afsar SI, Yemisci OU, Cetin N. The role of platelet-rich plasma in peripheral nerve injuries. J Clin Anal Med. 2015;6:905–8.
  • Firat C, Aytekin AH, Durak MA, Geyik Y, Erbatur S, Dogan M, et al. Comparison of the effects of PRP and hyaluronic acid in promoting peripheral nerve regeneration. Ann Ital Chir. 2016;87(4):362–74.
  • Zhang W, Li C, Yang S, Xu C, Wang W, Nyengaard JR, et al. A stereological method for estimating the total length and size of myelinated fibers in rat cerebral cortex. J Neurosci Methods. 2008;172(1):21–6.
  • Arindra PK, Rahmat M, Rahardjo R. Regenerasi Nervus Mentalis akibat Cedera Penjepitan setelah Aplikasi Kombinasi Platelet Rich Plasma yang Diaktivasi Spons Kolagen dan Cytidine 5’-Diphosphocholine. J Ked Gi. 2016;7(2):138–44.
  • Ikumi A, Hara Y, Yoshioka T, Kanamori A, Yamazaki M. Effect of local administration of platelet-rich plasma (PRP) on peripheral nerve regeneration: An experimental study in the rabbit model. Microsurgery. 2018;38(3):300–9.
  • Zavala A, Martinez PC, Gutierrez GG, Vara MD, Pawlikowski W De. The Combined Use of Curcumin and Platelet-Rich Plasma Enhances Axonal Regeneration in Acute Nerve Injuries: An Experimental Study in a Rat Model. J Hand Microsurg. 2023;15(1):31–6.
  • Pandunugrahadi M, Irianto KA, Sindrawati O. The Optimal Timing of Platelet-Rich Plasma (PRP) Injection for Nerve Lesion Recovery: A Preliminary Study. Int J Biomater. 2022;2022:1–7.
  • Wu CC, Wu YN, Ho HO, Chen KC, Sheu MT, Chiang HS. The neuroprotective effect of platelet-rich plasma on erectile function in bilateral cavernous nerve injury rat model. J Sex Med. 2012;9(11):2838–48.
  • Cámara-Lemarroy CR, Guzmán-de la Garza FJ, Barrera-Oranday EA, Cabello-García AJ, García-Tamez A, Fernández-Garza NE. Celecoxib accelerates functional recovery after sciatic nerve crush in the rat. J Brachial Plex Peripher Nerve Inj. 2008;3(01):e128–31.
  • Emril DR, Wibowo S, Meliala L, Susilowati R. Cytidine 5′-diphosphocholine administration prevents peripheral neuropathic pain after sciatic nerve crush injury in rats. J Pain Res. 2016;287–91.
  • Jaggi AS, Jain V, Singh N. Animal models of neuropathic pain. Vol. 25, Fundamental and Clinical Pharmacology. 2011. p. 1–28.
  • Emril D, Hajar S, Ismy J. Efikasi platelet rich plasma (PRP) terhadap optimalisasi pengobatan nyeri neuropatik dan perbaikan fungsi neurologi paska cedera saraf. Banda Aceh; 2021.
  • Muttaqien A. Peran Platelet Rich Plasma Terhadap Perbaikan Fungsi Motorik Pada Tikus Putih (Rattus Novergicus) Pasca Cedera Saraf Tepi. [Banda Aceh]: Faculty of Medicine, Syiah Kuala University; 2022.
  • Wu YN, Liao CH, Chen KC, Chiang HS. Dual effect of chitosan activated platelet rich plasma (cPRP) improved erectile function after cavernous nerve injury. J Formos Med Assoc. 2022;121(1):14–24.
  • Kokkalas N, Kokotis P, Diamantopoulou K, Galanos A, Lelovas P, Papachristou DJ, et al. Platelet-rich plasma and mesenchymal stem cells local infiltration promote functional recovery and histological repair of experimentally transected sciatic nerves in rats. Cureus. 2020;12(5).
  • García de Cortázar U, Padilla S, Lobato E, Delgado D, Sánchez M. Intraneural platelet-rich plasma injections for the treatment of radial nerve section: A case report. J Clin Med. 2018;7(2):13.
  • Karakaş DÖ, Dandin Ö, Müftüoğlu T, Tihan D, Bal AS, Yıldırım Ş. Effect of platelet-rich plasma on postoperative peritoneal inflammation and adhesions. Arch Med Sci. 2021;17(5):1408.
  • Fox IK, Brenner MJ, Johnson PJ, Hunter DA, MacKinnon SE. Axonal regeneration and motor neuron survival after microsurgical nerve reconstruction. Microsurgery. 2012;32(7):552–62.
  • Emril D, Hajar S, Ismy J, Muttaqien A, Maulina M. The Efficacy of Platelet Rich Plasma on Optimalization of Neurologic Function Improvement After Nerve Injury. In: The 14th Biennial Convention of The ASEAN Neurological Association. Bangkok: Neurological Society of Thailand; 2021.
  • Wasterlain AS, Braun HJ, Dragoo JL. The Systemic Effects of Platelet-Rich Plasma. In: Maffulli N, editor. Platelet Rich Plasma in Musculoskeletal Practice. London: Springer London; 2016. p. 199–222.
  • Wasterlain AS, Braun HJ, Harris AHS, Kim HJ, Dragoo JL. The systemic effects of platelet-rich plasma injection. Am J Sports Med. 2013;41(1):186–93.
  • Knop E, De Paula LE, Fuller R. Platelet-rich plasma for osteoarthritis treatment. Vol. 56, Revista Brasileira de Reumatologia. Elsevier Editora Ltda; 2016. p. 152–64.
  • Winias S, Radithia D, Parmadiati AE, Soebadi B, Ernawati DS, Hadi P, et al. Allogenous Freeze-Dried Platelet-Rich Plasma Promotes Peripheral Myelin Repair in Chronic Constriction Nerve Injury. Syst Rev Pharm. 2020;11(6).
  • Sánchez M, Garate A, Delgado D, Padilla S. Platelet-rich plasma, an adjuvant biological therapy to assist peripheral nerve repair. Neural Regen Res. 2017;12(1):47–52.
  • Moegni K, Ekaputri K, Biben J, Rosadi I, Rosliana I, Sobariah S, et al. Evaluation of plasma PDGF and VEGF levels after systemic administration of activated autologous platelet-rich plasma. Biomedicine (Taipei). 2021;41:409–12.
  • Ikumi A, Hara Y, Okano E, Kohyama S, Arai N, Taniguchi Y, et al. Intraoperative Local Administration of Platelet-Rich Plasma (PRP) during Neurolysis Surgery for the Treatment of Digital Nerve Crush Injury. Case Rep Orthop. 2018;6:1–6.
  • Sánchez M, Anitua E, Delgado D, Sanchez P, Prado R, Orive G, et al. Platelet-rich plasma, a source of autologous growth factors and biomimetic scaffold for peripheral nerve regeneration. Vol. 17, Expert Opinion on Biological Therapy. Taylor and Francis Ltd; 2017. p. 197–212.
  • Rayilla RSR, Naidu MUR, Babu PP. Surgically Induced Demyelination in Rat Sciatic Nerve. Brain Sci. 2023;13(5).
There are 41 citations in total.

Details

Primary Language English
Subjects Peripheral Nervous System
Journal Section Research Article
Authors

Meutia Maulina 0009-0000-3546-8920

Dessy Rakhmawati Emril 0000-0003-3859-9592

Endang Mutiawati 0000-0002-5116-2881

Etriwati Etriwati 0000-0001-5489-5282

Sri Hastuti 0009-0000-4111-0036

Safrizal Rahman 0000-0003-1265-8160

Zulkarnain Zulkarnain 0000-0002-5395-1892

Publication Date September 30, 2024
Submission Date June 11, 2024
Acceptance Date August 5, 2024
Published in Issue Year 2024 Volume: 41 Issue: 3

Cite

APA Maulina, M., Emril, D. R., Mutiawati, E., Etriwati, E., et al. (2024). Effects of different platelet-rich plasma administration methods on peripheral nerve regeneration: A histomorphometric study. Journal of Experimental and Clinical Medicine, 41(3), 557-562.
AMA Maulina M, Emril DR, Mutiawati E, Etriwati E, Hastuti S, Rahman S, Zulkarnain Z. Effects of different platelet-rich plasma administration methods on peripheral nerve regeneration: A histomorphometric study. J. Exp. Clin. Med. September 2024;41(3):557-562.
Chicago Maulina, Meutia, Dessy Rakhmawati Emril, Endang Mutiawati, Etriwati Etriwati, Sri Hastuti, Safrizal Rahman, and Zulkarnain Zulkarnain. “Effects of Different Platelet-Rich Plasma Administration Methods on Peripheral Nerve Regeneration: A Histomorphometric Study”. Journal of Experimental and Clinical Medicine 41, no. 3 (September 2024): 557-62.
EndNote Maulina M, Emril DR, Mutiawati E, Etriwati E, Hastuti S, Rahman S, Zulkarnain Z (September 1, 2024) Effects of different platelet-rich plasma administration methods on peripheral nerve regeneration: A histomorphometric study. Journal of Experimental and Clinical Medicine 41 3 557–562.
IEEE M. Maulina, “Effects of different platelet-rich plasma administration methods on peripheral nerve regeneration: A histomorphometric study”, J. Exp. Clin. Med., vol. 41, no. 3, pp. 557–562, 2024.
ISNAD Maulina, Meutia et al. “Effects of Different Platelet-Rich Plasma Administration Methods on Peripheral Nerve Regeneration: A Histomorphometric Study”. Journal of Experimental and Clinical Medicine 41/3 (September 2024), 557-562.
JAMA Maulina M, Emril DR, Mutiawati E, Etriwati E, Hastuti S, Rahman S, Zulkarnain Z. Effects of different platelet-rich plasma administration methods on peripheral nerve regeneration: A histomorphometric study. J. Exp. Clin. Med. 2024;41:557–562.
MLA Maulina, Meutia et al. “Effects of Different Platelet-Rich Plasma Administration Methods on Peripheral Nerve Regeneration: A Histomorphometric Study”. Journal of Experimental and Clinical Medicine, vol. 41, no. 3, 2024, pp. 557-62.
Vancouver Maulina M, Emril DR, Mutiawati E, Etriwati E, Hastuti S, Rahman S, Zulkarnain Z. Effects of different platelet-rich plasma administration methods on peripheral nerve regeneration: A histomorphometric study. J. Exp. Clin. Med. 2024;41(3):557-62.