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Kafa travması sonrası elde edilen beyin omurilik sıvısının sıçan kırık modelinde osteojenik potansiyeli

Yıl 2025, Cilt: 50 Sayı: 4, 1013 - 1024, 22.12.2025
https://doi.org/10.17826/cumj.1670756

Öz

Amaç: Travmatik beyin hasarı sonrası hızlanmış kırık iyileşmesi literatürde bildirilmiş olmasına rağmen, bu sürecin altında yatan mekanizmalar henüz netlik kazanmamıştır. Bu çalışmada, travmatik beyin hasarı sonrası sistemik dolaşıma katılan beyin omurilik sıvısının kırık iyileşmesini hızlandırabileceği hipotezini öne sürdük. Bu hipotezi test etmek amacıyla, travmatik beyin hasarı sonrası elde edilen beyin omurilik sıvısının sıçan modelinde kırık iyileşmesi üzerindeki etkilerini değerlendirmeyi amaçladık.
Gereç ve Yöntem: Çalışmaya toplam 39 erkek Wistar albino sıçan dahil edilerek üç gruba ayrıldı: kontrol grubu (n=15), deney grubu (n=14) ve kafa travması grubu (n=10). Kafa travması grubundaki sıçanlara deneysel kafa travması uygulandı ve bu sıçanlardan beyin omurilik sıvısı elde edildi. Kontrol ve deney gruplarında femur kırıkları oluşturularak intramedüller tespit uygulandı. Deney grubundaki sıçanların kırık bölgesine, kafa travması grubundan elde edilen beyin omurilik sıvısı enjekte edildi. Çalışmanın 30. gününde femurlar dezartiküle edildi ve kallus dokusu uzunluk ve genişlik açısından radyolojik olarak, histolojik olarak ise Huo derecelendirme sistemi kullanılarak değerlendirildi.
Bulgular: Deney grubunda kallus doku uzunluğu ortalama 11,96 ± 3,29 mm iken, kontrol grubunda 6,96 ± 3,30 mm olarak ölçülmüştür. Deney grubunun kallus doku uzunluğu kontrol grubuna kıyasla istatistiksel olarak anlamlı derecede daha yüksek bulunmuştur. Kallus doku kalınlığı ise deney grubunda 1,51 ± 0,60 mm, kontrol grubunda 1,17 ± 0,58 mm olarak saptanmış olup, iki grup arasında istatistiksel olarak anlamlı bir fark izlenmemiştir. Deney grubunun kallus maturasyon skoru (6,71 ± 0,73), kontrol grubuna (5,67 ± 1,05) kıyasla istatistiksel olarak anlamlı derecede daha yüksek bulunmuştur.
Sonuç: Travmatik beyin hasarı sonrası hızlanmış kırık iyileşmesinin mekanizması tam olarak aydınlatılamamıştır. Bu çalışmada, travmatik beyin hasarı sonrası elde edilen beyin omurilik sıvısının sıçan modelinde histolojik olarak anlamlı derecede kırık iyileşmesini hızlandırdığı ve kallus uzunluğunu artırdığı gösterilmiştir.

Proje Numarası

05042013

Kaynakça

  • Xiong Y, Zhong W, Mi B. The mechanism of bone healing after traumatic brain injury. Brain-X. 2023;1:e31.
  • Lawand J, Loeffelholz Z, Khurshid B, Barcak E. Heterotopic ossification after trauma. Orthop Clin North Am. 2023;54:37–46.
  • Schincariol CYN, Echauri EMI, Silvestre OF, Cliquet A. Heterotopic ossification after spinal cord injury: prevention and treatment—a systematic review. Acta Ortop Bras. 2023;31:e267451.
  • Roberts PH. Heterotopic ossification complicating paralysis of intracranial origin. J Bone Joint Surg Br. 1968;50:70–7.
  • Perkins R, Skirving AP. Callus formation and the rate of healing of femoral fractures in patients with head injuries. J Bone Joint Surg Br. 1987;69:521–4.
  • Bidner SM, Rubins IM, Desjardins JV, Zukor DJ, Goltzman D. Evidence for a humoral mechanism for enhanced osteogenesis after head injury. J Bone Joint Surg Am. 1990;72:1144–9.
  • Sabet N, Soltani Z, Khaksari M. Multipotential and systemic effects of traumatic brain injury. J Neuroimmunol. 2021;357:577619.
  • Renfree KJ, Banovac K, Hornicek FJ, Lebwohl NH, Villanueva PA, Nedd KJ. Evaluation of serum osteoblast mitogenic activity in spinal cord and head injury patients with acute heterotopic ossification. Spine (Phila Pa 1976). 1994;19:740–6.
  • Gautschi OP, Toffoli AM, Joesbury KA, Skirving AP, Filgueira L, Zellweger R. Osteoinductive effect of cerebrospinal fluid from brain-injured patients. J Neurotrauma. 2007;24:154–62.
  • Gardner MJ, van der Meulen MCH, Demetrakopoulos D, Wright TM, Myers ER, Bostrom MP. In vivo cyclic axial compression affects bone healing in the mouse tibia. J Orthop Res. 2006;24:1679–86.
  • Marmarou A, Foda MAAE, Van Den Brink W, Campbell J, Kita H, Demetriadou K. A new model of diffuse brain injury in rats: Part I: Pathophysiology and biomechanics. J Neurosurg. 1994;80:291–300.
  • Liu L, Duff K. A technique for serial collection of cerebrospinal fluid from the cisterna magna in mouse. J Vis Exp. 2008;21:960.
  • Schindler CR, Lustenberger T, Woschek M, Störmann P, Henrich D, Radermacher P et al. Severe traumatic brain injury modulates the kinetic profile of the inflammatory response of markers for neuronal damage. J Clin Med. 2020;9:1667.
  • Chang WS, Huang CC, Chen TH, Chao SH, Lin CH, Chang CP et al. Hyperbaric oxygen potentiates platelet-rich plasma composition and accelerates bone healing. J Orthop Translat. 2025;51:1–12.
  • Açan AE, Aydın ME, Bulmuş Ö, Özcan E, Karakılıç A, Turan G et al. Irisin and its role in fracture healing: a comparative study with hyaluronic acid and platelet-rich plasma in a rat model. Jt Dis Relat Surg. 2025;36:328.
  • Simman R, Hoffmann A, Bohinc RJ, Peterson WC, Russ AJ. Role of platelet-rich plasma in acceleration of bone fracture healing. Ann Plast Surg. 2008;61:337–44.
  • Lane JM, Sandhu HS. Current approaches to experimental bone grafting. Orthop Clin North Am. 1987;18:213–25.
  • Huo MH. The influence of ibuprofen on fracture repair: biomechanical, biochemical, histologic, and histomorphometric parameters in rats. J Orthop Res. 1991;9:383–90.
  • Jin Z, Chen Z, Liang T, Liu W, Shan Z, Tan D et al. Accelerated fracture healing accompanied with traumatic brain injury: a review of clinical studies, animal models and potential mechanisms. J Orthop Translat. 2025;50:71–84.
  • Boes M, Kain M, Kakar S, Nicholls F, Cullinane D, Gerstenfeld L et al. Osteogenic effects of traumatic brain injury on experimental fracture healing. J Bone Joint Surg Am. 2006;88:738–43.
  • Arık M, Ekinci Y, Gürbüz K, Batın S. The effects of focal brain damage on fracture healing: an experimental rat study. Jt Dis Relat Surg. 2019;30:267–74.
  • Cadosch D, Gautschi OP, Thyer M, Song S, Skirving AP, Filgueira L et al. Humoral factors enhance fracture healing and callus formation in patients with traumatic brain injury. J Bone Joint Surg Am. 2009;91:282–8.
  • Sarı A, Dinçel YM, Çetin MÜ, İnan S. Can fracture healing be accelerated by serum transfer in head trauma cases? an experimental head trauma model in rats. Jt Dis Relat Surg. 2021;32:306.
  • Huang GY, Ma X, Xia XL, Jiang JY, Jin WF, Gao JJ et al. Effect of rat brain tissue extracts on osteoblast proliferation and differentiation. Int Orthop. 2012;36:887–93.
  • Liu Q, Lei L, Yu T, Jiang T, Kang Y. Effect of brain-derived neurotrophic factor on the neurogenesis and osteogenesis in bone engineering. Tissue Eng Part A. 2018;24:1283–92.
  • Xia W, Xie J, Cai Z, Liu X, Wen J, Cui ZK et al. Damaged brain accelerates bone healing by releasing small extracellular vesicles that target osteoprogenitors. Nat Commun. 2021;12:6043.
  • Papachristou DJ, Georgopoulos S, Giannoudis PV, Panagiotopoulos E. Insights into the cellular and molecular mechanisms that govern the fracture healing process: a narrative review. J Clin Med. 2021;10:3554

The osteogenic potential of cerebrospinal fluid obtained after traumatic brain injury in a rat fracture model

Yıl 2025, Cilt: 50 Sayı: 4, 1013 - 1024, 22.12.2025
https://doi.org/10.17826/cumj.1670756

Öz

Purpose: Accelerated fracture healing following traumatic brain injury was reported in the literature, yet the underlying mechanisms remain unclear. This study hypothesizes that cerebrospinal fluid entering systemic circulation after traumatic brain injury contributes to the acceleration of fracture healing. To test this hypothesis, we aimed to evaluate the effects of cerebrospinal fluid collected post-traumatic brain injury on fracture healing in a rat model.
Materials and Methods: A total of 39 male Wistar albino rats were divided into three groups: control group (n=15), experimental group (n=14), and head trauma group (n=10). Head trauma was induced in the head trauma group, and cerebrospinal fluid was collected from the 10 rats following trauma. Femur fractures were induced and intramedullary fixation was performed in the control and experimental groups. Cerebrospinal fluid from the head trauma group was injected into the fracture site of the experimental group. On the 30th day, femurs were disarticulated, and callus tissue was evaluated radiologically for length and width and histologically using the Huo grading system.
Results: In the experimental group, the mean callus tissue length was 11.96 ± 3.29 mm, whereas in the control group it was 6.96 ± 3.30 mm. The callus tissue length in the experimental group was significantly higher compared to the control group. Callus tissue thickness was measured as 1.51 ± 0.60 mm in the experimental group and 1.17 ± 0.58 mm in the control group, with no statistically significant difference between the groups. The callus maturation score in the experimental group (6.71 ± 0.73) was significantly higher compared to the control group (5.67 ± 1.05).
Conclusion: The mechanism underlying accelerated fracture healing after traumatic brain injury remains elusive. In this study, cerebrospinal fluid collected post-traumatic brain injury demonstrated histologically significant acceleration of fracture healing and increased callus length.

Etik Beyan

Prior to the study, the necessary approvals were obtained from the Local Ethics Committee for Animal Experiments of Çukurova University, Republic of Turkey

Destekleyen Kurum

Çukurova University Faculty of Medicine

Proje Numarası

05042013

Teşekkür

We would like to express our gratitude to Prof. Dr. Gülfiliz Gönlüşen for her valuable assistance in the evaluation of bone preparations. We also thank Prof. Dr.Kenan Dağlıoğlu for his support during the animal experiments.

Kaynakça

  • Xiong Y, Zhong W, Mi B. The mechanism of bone healing after traumatic brain injury. Brain-X. 2023;1:e31.
  • Lawand J, Loeffelholz Z, Khurshid B, Barcak E. Heterotopic ossification after trauma. Orthop Clin North Am. 2023;54:37–46.
  • Schincariol CYN, Echauri EMI, Silvestre OF, Cliquet A. Heterotopic ossification after spinal cord injury: prevention and treatment—a systematic review. Acta Ortop Bras. 2023;31:e267451.
  • Roberts PH. Heterotopic ossification complicating paralysis of intracranial origin. J Bone Joint Surg Br. 1968;50:70–7.
  • Perkins R, Skirving AP. Callus formation and the rate of healing of femoral fractures in patients with head injuries. J Bone Joint Surg Br. 1987;69:521–4.
  • Bidner SM, Rubins IM, Desjardins JV, Zukor DJ, Goltzman D. Evidence for a humoral mechanism for enhanced osteogenesis after head injury. J Bone Joint Surg Am. 1990;72:1144–9.
  • Sabet N, Soltani Z, Khaksari M. Multipotential and systemic effects of traumatic brain injury. J Neuroimmunol. 2021;357:577619.
  • Renfree KJ, Banovac K, Hornicek FJ, Lebwohl NH, Villanueva PA, Nedd KJ. Evaluation of serum osteoblast mitogenic activity in spinal cord and head injury patients with acute heterotopic ossification. Spine (Phila Pa 1976). 1994;19:740–6.
  • Gautschi OP, Toffoli AM, Joesbury KA, Skirving AP, Filgueira L, Zellweger R. Osteoinductive effect of cerebrospinal fluid from brain-injured patients. J Neurotrauma. 2007;24:154–62.
  • Gardner MJ, van der Meulen MCH, Demetrakopoulos D, Wright TM, Myers ER, Bostrom MP. In vivo cyclic axial compression affects bone healing in the mouse tibia. J Orthop Res. 2006;24:1679–86.
  • Marmarou A, Foda MAAE, Van Den Brink W, Campbell J, Kita H, Demetriadou K. A new model of diffuse brain injury in rats: Part I: Pathophysiology and biomechanics. J Neurosurg. 1994;80:291–300.
  • Liu L, Duff K. A technique for serial collection of cerebrospinal fluid from the cisterna magna in mouse. J Vis Exp. 2008;21:960.
  • Schindler CR, Lustenberger T, Woschek M, Störmann P, Henrich D, Radermacher P et al. Severe traumatic brain injury modulates the kinetic profile of the inflammatory response of markers for neuronal damage. J Clin Med. 2020;9:1667.
  • Chang WS, Huang CC, Chen TH, Chao SH, Lin CH, Chang CP et al. Hyperbaric oxygen potentiates platelet-rich plasma composition and accelerates bone healing. J Orthop Translat. 2025;51:1–12.
  • Açan AE, Aydın ME, Bulmuş Ö, Özcan E, Karakılıç A, Turan G et al. Irisin and its role in fracture healing: a comparative study with hyaluronic acid and platelet-rich plasma in a rat model. Jt Dis Relat Surg. 2025;36:328.
  • Simman R, Hoffmann A, Bohinc RJ, Peterson WC, Russ AJ. Role of platelet-rich plasma in acceleration of bone fracture healing. Ann Plast Surg. 2008;61:337–44.
  • Lane JM, Sandhu HS. Current approaches to experimental bone grafting. Orthop Clin North Am. 1987;18:213–25.
  • Huo MH. The influence of ibuprofen on fracture repair: biomechanical, biochemical, histologic, and histomorphometric parameters in rats. J Orthop Res. 1991;9:383–90.
  • Jin Z, Chen Z, Liang T, Liu W, Shan Z, Tan D et al. Accelerated fracture healing accompanied with traumatic brain injury: a review of clinical studies, animal models and potential mechanisms. J Orthop Translat. 2025;50:71–84.
  • Boes M, Kain M, Kakar S, Nicholls F, Cullinane D, Gerstenfeld L et al. Osteogenic effects of traumatic brain injury on experimental fracture healing. J Bone Joint Surg Am. 2006;88:738–43.
  • Arık M, Ekinci Y, Gürbüz K, Batın S. The effects of focal brain damage on fracture healing: an experimental rat study. Jt Dis Relat Surg. 2019;30:267–74.
  • Cadosch D, Gautschi OP, Thyer M, Song S, Skirving AP, Filgueira L et al. Humoral factors enhance fracture healing and callus formation in patients with traumatic brain injury. J Bone Joint Surg Am. 2009;91:282–8.
  • Sarı A, Dinçel YM, Çetin MÜ, İnan S. Can fracture healing be accelerated by serum transfer in head trauma cases? an experimental head trauma model in rats. Jt Dis Relat Surg. 2021;32:306.
  • Huang GY, Ma X, Xia XL, Jiang JY, Jin WF, Gao JJ et al. Effect of rat brain tissue extracts on osteoblast proliferation and differentiation. Int Orthop. 2012;36:887–93.
  • Liu Q, Lei L, Yu T, Jiang T, Kang Y. Effect of brain-derived neurotrophic factor on the neurogenesis and osteogenesis in bone engineering. Tissue Eng Part A. 2018;24:1283–92.
  • Xia W, Xie J, Cai Z, Liu X, Wen J, Cui ZK et al. Damaged brain accelerates bone healing by releasing small extracellular vesicles that target osteoprogenitors. Nat Commun. 2021;12:6043.
  • Papachristou DJ, Georgopoulos S, Giannoudis PV, Panagiotopoulos E. Insights into the cellular and molecular mechanisms that govern the fracture healing process: a narrative review. J Clin Med. 2021;10:3554
Toplam 27 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Ortopedi
Bölüm Araştırma Makalesi
Yazarlar

Alaaddin Levent Özgözen 0000-0002-0479-3074

Nazlı Soygun Bu kişi benim 0000-0002-1318-6831

İsmet Tan Bu kişi benim 0009-0005-3884-1301

Proje Numarası 05042013
Gönderilme Tarihi 18 Mayıs 2025
Kabul Tarihi 8 Kasım 2025
Yayımlanma Tarihi 22 Aralık 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 50 Sayı: 4

Kaynak Göster

MLA Özgözen, Alaaddin Levent, vd. “The osteogenic potential of cerebrospinal fluid obtained after traumatic brain injury in a rat fracture model”. Cukurova Medical Journal, c. 50, sy 4, Aralık 2025, ss. 1013-24, doi:10.17826/cumj.1670756.