Deneysel Modellerde Stereotaksik Cerrahi Uygulaması

Yazarlar

Özet

Bu bölüm, deneysel sinirbilim araştırmalarında temel bir yöntem olan stereotaksik cerrahiye ilişkin kapsamlı bir değerlendirme sunmaktadır. Üç boyutlu bir koordinat sistemi kullanılarak belirli beyin yapılarının yüksek hassasiyetle hedeflenmesini sağlayan bu teknik, ilk olarak 20. yüzyılın başlarında Horsley ve Clarke tarafından geliştirilmiştir. Stereotaksi, günümüzde nöroanatomik haritalama, lezyon çalışmaları ve intraserebral ilaç uygulamaları gibi çok çeşitli araştırma alanlarında vazgeçilmez bir yöntemdir. Bölümde stereotaksik cihazın tarihsel gelişimi, kuramsal temelleri ve mekanik bileşenleri ele alınmakta; bregma ve lambda referans noktalarının doğru hizalanmasıyla “düz kafatası pozisyonunun” korunmasının deneysel doğruluk açısından kritik önemi vurgulanmaktadır. Vernier skalasının okunması, koordinatların ayarlanması ve hassas mikro konumlandırma süreçleri ayrıntılı biçimde açıklanmıştır. Uygulama örneği olarak, Substantia nigra’nın retiküler alt bölümüne (SNR) stereotaksik olarak ulaşma süreci, Paxinos ve Watson sıçan beyin atlası esas alınarak adım adım tanımlanmıştır. Yöntemsel açıklamalar güncel literatür desteğiyle birlikte değerlendirilmiş; deneysel hassasiyet, tekrarlanabilirlik ve ulusal/kurumsal etik standartlara uyum konularına özel vurgu yapılmıştır. Bu bölüm, stereotaksik müdahaleleri yüksek doğrulukla gerçekleştirmek isteyen araştırmacılar için kuramsal ve uygulamalı bir rehber oluşturmayı amaçlamaktadır.

This chapter provides a comprehensive evaluation of stereotaxic surgery, a cornerstone technique in experimental neuroscience that enables the precise targeting of specific brain structures using a three-dimensional coordinate system. Originally developed by Horsley and Clarke in the early twentieth century, stereotaxy remains indispensable in contemporary research, including neuroanatomical mapping, lesion studies, and intracerebral drug administration. The chapter discusses the historical development, theoretical foundations, and mechanical components of the stereotaxic apparatus, with particular emphasis on the importance of maintaining the flat skull position through accurate alignment of bregma and lambda reference points. Detailed procedures are presented for reading the vernier scale, setting coordinates, and performing precise micro-positioning. As an illustrative example, the step-by-step targeting of the reticular subdivision of the Substantia nigra (SNR) is described using the Paxinos and Watson rat brain atlas. Methodological explanations are supported by current literature and address issues of experimental precision, reproducibility, and compliance with national and institutional ethical guidelines for animal research. By integrating theoretical and practical perspectives, this chapter serves as a methodological guide for researchers aiming to perform high-accuracy stereotaxic interventions in neuroscience studies.

Referanslar

Horsley V, Clarke Rh. The Structure And Functions Of The Cerebellum Examined By A New Method. Brain. 1908;31(1):45-124.

Grunert Sr P, Keiner D, Oertel J. Remarks upon the Term Stereotaxy: A Linguistic and Historical Note. Stereotactic and Functional Neurosurgery. 2015;93(1):42-9.

Clarke RH, Horsley V. THE CLASSIC: On a method of investigating the deep ganglia and tracts of the central nervous system (cerebellum). Br Med J 1906:1799-1800. Clin Orthop Relat Res. 2007;463:3-6.

Ferry B, Gervasoni D. Improving Stereotaxic Neurosurgery Techniques and Procedures Greatly Reduces the Number of Rats Used per Experimental Group-A Practice Report. Animals (Basel). 2021;11(9).

Blomstedt P, Olivecrona M, Sailer A, Hariz MI. Dittmar and the history of stereotaxy; or rats, rabbits, and references. Neurosurgery. 2007;60(1):198-201; discussion -2.

Rahman M, Murad GJ, Mocco J. Early history of the stereotactic apparatus in neurosurgery. Neurosurg Focus. 2009;27(3):E12.

Spiegel EA, Wycis HT, Marks M, Lee AJ. Stereotaxic Apparatus for Operations on the Human Brain. Science. 1947;106(2754):349-50.

Kwoh YS, Hou J, Jonckheere EA, Hayati S. A robot with improved absolute positioning accuracy for CT guided stereotactic brain surgery. IEEE Trans Biomed Eng. 1988;35(2):153-60.

Trifiletti DM, Ruiz-Garcia H, Quinones-Hinojosa A, Ramakrishna R, Sheehan JP. The evolution of stereotactic radiosurgery in neurosurgical practice. J Neurooncol. 2021;151(3):451-9.

Nashold BS. The History of Stereotactic Neurosurgery. Stereotactic and Functional Neurosurgery. 1995;62(1-4):29-40.

Grunert P. From the idea to its realization: the evolution of minimally invasive techniques in neurosurgery. Minim Invasive Surg. 2013;2013:171369.

Nüssel M, Zhao Y, Knorr C, Regensburger M, Stadlbauer A, Buchfelder M, et al. Deep Brain Stimulation, Stereotactic Radiosurgery and High-Intensity Focused Ultrasound Targeting the Limbic Pain Matrix: A Comprehensive Review. Pain Ther. 2022;11(2):459-76.

Faillot M, Chaillet A, Palfi S, Senova S. Rodent models used in preclinical studies of deep brain stimulation to rescue memory deficits. Neuroscience & Biobehavioral Reviews. 2021;130:410-32.

Russell WMS, Burch RL. The Principles of Humane Experimental Technique: Methuen; 1959.

Kehr J, Karolinska. Modern Techniques in Neuroscience Research. 1999.

Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates. Compact seventh edition. ed. London, England: Academic Press; 2018.

McSweeney C, Mao Y. Applying Stereotactic Injection Technique to Study Genetic Effects on Animal Behaviors. JoVE. 2015(99):e52653.

Ferry B, Gervasoni D. Improving Stereotaxic Neurosurgery Techniques and Procedures Greatly Reduces the Number of Rats Used per Experimental Group—A Practice Report. Animals [Internet]. 2021; 11(9).

Zapata A, Chefer VI, Shippenberg TS. Microdialysis in rodents. Curr Protoc Neurosci. 2009;Chapter 7:Unit7.2.

Au - Fornari RV, Au - Wichmann R, Au - Atsak P, Au - Atucha E, Au - Barsegyan A, Au - Beldjoud H, et al. JoVE. 2012(59):e3528.

Pérez-Martín E, Coto-Vilcapoma A, Castilla-Silgado J, Rodríguez-Cañón M, Prado C, Álvarez G, et al. Refining Stereotaxic Neurosurgery Techniques and Welfare Assessment for Long-Term Intracerebroventricular Device Implantation in Rodents. Animals [Internet]. 2023; 13(16).

Ferry B, Gervasoni D, Vogt C. Stereotaxic neurosurgery in laboratory rodent : handbook on best practices. Paris: Springer; 2014.

Athos J, Storm D. High Precision Stereotaxic Surgery in Mice. Current protocols in neuroscience / editorial board, Jacqueline N Crawley [et al]. 2001;Appendix 4:Appendix 4A.

Ly PT, Lucas A, Pun SH, Dondzillo A, Liu C, Klug A, et al. Robotic Stereotaxic System based on 3D skull reconstruction to improve surgical accuracy and speed. bioRxiv. 2020:2020.01.04.894972.

Pak N, Siegle JH, Kinney JP, Denman DJ, Blanche TJ, Boyden ES. Closed-loop, ultraprecise, automated craniotomies. J Neurophysiol. 2015;113(10):3943-53.

Co. S. Lab standard stereotaxic instrument [Internet]. 2024 [updated cited October 27, 2025]. Available from: https://stoeltingco.com/Neuroscience/Lab-Standard-Stereotaxic-Instrument~9649.

Scouten CW. Stereotaxic Accuracy [Internet]. Leica Biosystems. ; 2024 [updated cited October 27, 2025]. Available from: https://www.leicabiosystems.com/us/knowledge-pathway/stereotaxic-accuracy/.

Britannica BiE. Vernier caliper [Internet]. Encyclopedia Britannica; 2024 [updated cited October 27, 2025]. Available from: https://www.britannica.com/technology/vernier-caliper.

O'Connor JJ, Robertson EF. Biography of Pierre Vernier [Internet]. MacTutor Index; 2024 [updated cited October 27, 2025].Available from: https://mathshistory.st-andrews.ac.uk/Biographies/Vernier.

JoVE. Rodent Stereotaxic Surgery [Video] [Internet]. [updated cited Available from: https://www.jove.com/v/5205/rodent-stereotaxic-surgery.

Instruments K. Micro Manipulators Models 1760, 1760-61 [Internet]. [updated cited Available from: https://kopfinstruments.com/product/micro-manipulators-models-1760-1760-61/.

Europe W. Reading a Vernier Scale [Internet]. 2024 [updated cited October 28, 2025]. Available from: https://www.wpi-europe.com/solutions/micromanipulators-knowledgebase/line-up-reading-a-vernier-scale.aspx.

International P. Small Animal Stereotaxic Instrument [Internet]. [updated cited Available from: https://protechinternational.com/products/small-animal-stereotaxic-instrument.

Hankenson FC, Kim JJ, Le TM, Lawrence FR, Del Valle JM. Using Waterless Alcohol-based Antiseptic for Skin Preparation and Active Thermal Support in Laboratory Rats. J Am Assoc Lab Anim Sci. 2021;60(3):365-73.

Bailey KT, Jantre SR, Lawrence FR, Hankenson FC, Del Valle JM. Evaluation of Active Warming and Surgical Draping for Perioperative Thermal Support in Laboratory Mice. J Am Assoc Lab Anim Sci. 2022;61(5):482-94.

He X, Jia L, Zhang X. The Effect of Different Preoperative Depilation Ways on the Healing of Wounded Skin in Mice. Animals (Basel). 2022;12(5).

Kroner KT, Budgeon C, Colopy SA. Update on Surgical Principles and Equipment. Vet Clin North Am Exot Anim Pract. 2016;19(1):13-32.

Barahona MJ, Rojas J, Uribe EA, García-Robles MA. Tympanic Membrane Rupture During Stereotaxic Surgery Disturbs the Normal Feeding Behavior in Rats. Frontiers in Behavioral Neuroscience. 2020;Volume 14 - 2020.

Shimizu K, Fukada Y. Stereotaxic Surgery for Suprachiasmatic Nucleus Lesions in Mice. Bio-protocol. 2017;7(12):e2346.

Chelsea L. Faber; Miles E. Matsen; Thomas H. Meek PJEKGJM, PhD A customizable procedure for angled stereotaxic implantation and microinjection in the rodent brain. 2019.

Puntel M, Kroeger K, Sanderson N, Thomas C, Castro M, Lowenstein P. Gene Transfer into Rat Brain Using Adenoviral Vectors. Current protocols in neuroscience / editorial board, Jacqueline N Crawley [et al]. 2010;Chapter 4:Unit 4.24.

Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates. 6th ed. London: Academic Press; 2008.

Paxinos G, Watson C, Pennisi M, Topple A. Bregma, lambda and the interaural midpoint in stereotaxic surgery with rats of different sex, strain and weight. Journal of Neuroscience Methods. 1985;13(2):139-43.

De Vloo P, Nuttin B. Stereotaxy in rat models: Current state of the art, proposals to improve targeting accuracy and reporting guideline. Behavioural Brain Research. 2019;364:457-63.

Cecyn MN, Abrahao KP. Where do you measure the Bregma for rodent stereotaxic surgery? IBRO Neuroscience Reports. 2023;15:143-8.

Blasiak T, Czubak W, Ignaciak A, Lewandowski MH. A new approach to detection of the bregma point on the rat skull. Journal of Neuroscience Methods. 2010;185(2):199-203.

Kline J, Reid KH. Variability of bregma in 300 gram Long-Evans and Sprague-Dawley rats. Physiology & Behavior. 1984;33(2):301-3.

Ferry B, Gervasoni D. Improving Stereotaxic Neurosurgery Techniques and Procedures Greatly Reduces the Number of Rats Used per Experimental Group—A Practice Report. Animals. 2021;11(9):2662.

Whishaw IQ, Cioe JDD, Previsich N, Kolb B. The variability of the interaural line vs the stability of bregma in rat stereotaxic surgery. Physiology & Behavior. 1977;19(6):719-22.

Slotnick BM, Brown DL. Variability in the stereotaxic position of cerebral points in the albino rat. Brain Research Bulletin. 1980;5(2):135-9.

Yang P, Wang Z, Zhang Z, Liu D, Manolios EN, Chen C, et al. The extended application of The Rat Brain in Stereotaxic Coordinates in rats of various body weight. Journal of Neuroscience Methods. 2018;307:60-9.

Bao D, Su Y. Stereotaxic Atlas of the Rat Brain [in Chinese]. Beijing: Science Press; 1991.

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