Takashi D Y Kozai1, James R Eles2, Alberto L Vazquez3, X Tracy Cui4. 1. Bioengineering, University of Pittsburgh, USA; Center for the Neural Basis of Cognition, University of Pittsburgh, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, USA; NeuroTech Center of the University of Pittsburgh Brain Institute, USA. Electronic address: tdk18@pitt.edu. 2. Bioengineering, University of Pittsburgh, USA; Center for the Neural Basis of Cognition, University of Pittsburgh, USA. 3. Bioengineering, University of Pittsburgh, USA; Center for the Neural Basis of Cognition, University of Pittsburgh, USA; Radiology, University of Pittsburgh, USA. 4. Bioengineering, University of Pittsburgh, USA; Center for the Neural Basis of Cognition, University of Pittsburgh, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, USA. Electronic address: xic11@pitt.edu.
Abstract
BACKGROUND: Two-photon microscopy has enabled the visualization of dynamic tissue changes to injury and disease in vivo. While this technique has provided powerful new information, in vivo two-photon chronic imaging around tethered cortical implants, such as microelectrodes or neural probes, present unique challenges. NEW METHOD: A number of strategies are described to prepare a cranial window to longitudinally observe the impact of neural probes on brain tissue and vasculature for up to 3 months. RESULTS: It was found that silastic sealants limit cell infiltration into the craniotomy, thereby limiting light scattering and preserving window clarity over time. In contrast, low concentration hydrogel sealants failed to prevent cell infiltration and their use at high concentration displaced brain tissue and disrupted probe performance. COMPARISON WITH EXISTING METHOD(S): The use of silastic sealants allows for a suitable imaging window for long term chronic experiments and revealed new insights regarding the dynamic leukocyte response around implants and the nature of chronic BBB leakage in the sub-dural space. CONCLUSION: The presented method provides a valuable tool for evaluating the chronic inflammatory response and the performance of emerging implantable neural technologies.
BACKGROUND: Two-photon microscopy has enabled the visualization of dynamic tissue changes to injury and disease in vivo. While this technique has provided powerful new information, in vivo two-photon chronic imaging around tethered cortical implants, such as microelectrodes or neural probes, present unique challenges. NEW METHOD: A number of strategies are described to prepare a cranial window to longitudinally observe the impact of neural probes on brain tissue and vasculature for up to 3 months. RESULTS: It was found that silastic sealants limit cell infiltration into the craniotomy, thereby limiting light scattering and preserving window clarity over time. In contrast, low concentration hydrogel sealants failed to prevent cell infiltration and their use at high concentration displaced brain tissue and disrupted probe performance. COMPARISON WITH EXISTING METHOD(S): The use of silastic sealants allows for a suitable imaging window for long term chronic experiments and revealed new insights regarding the dynamic leukocyte response around implants and the nature of chronic BBB leakage in the sub-dural space. CONCLUSION: The presented method provides a valuable tool for evaluating the chronic inflammatory response and the performance of emerging implantable neural technologies.
Authors: T D Y Kozai; T C Marzullo; F Hooi; N B Langhals; A K Majewska; E B Brown; D R Kipke Journal: J Neural Eng Date: 2010-07-19 Impact factor: 5.379
Authors: Wolfgang Mittmann; Damian J Wallace; Uwe Czubayko; Jan T Herb; Andreas T Schaefer; Loren L Looger; Winfried Denk; Jason N D Kerr Journal: Nat Neurosci Date: 2011-07-10 Impact factor: 24.884
Authors: Vaclav Masopust; Martin Häckel; David Netuka; Ondrej Bradác; Richard Rokyta; Michal Vrabec Journal: Clin J Pain Date: 2009-09 Impact factor: 3.442
Authors: Amelia A Schendel; Michael W Nonte; Corinne Vokoun; Thomas J Richner; Sarah K Brodnick; Farid Atry; Seth Frye; Paige Bostrom; Ramin Pashaie; Sanitta Thongpang; Kevin W Eliceiri; Justin C Williams Journal: J Neural Eng Date: 2014-06-18 Impact factor: 5.379
Authors: Leigh R Hochberg; Daniel Bacher; Beata Jarosiewicz; Nicolas Y Masse; John D Simeral; Joern Vogel; Sami Haddadin; Jie Liu; Sydney S Cash; Patrick van der Smagt; John P Donoghue Journal: Nature Date: 2012-05-16 Impact factor: 49.962
Authors: Zhanhong Jeff Du; Christi L Kolarcik; Takashi D Y Kozai; Silvia D Luebben; Shawn A Sapp; Xin Sally Zheng; James A Nabity; X Tracy Cui Journal: Acta Biomater Date: 2017-02-06 Impact factor: 8.947
Authors: Takashi D Y Kozai; Andrea S Jaquins-Gerstl; Alberto L Vazquez; Adrian C Michael; X Tracy Cui Journal: Biomaterials Date: 2016-02-10 Impact factor: 12.479
Authors: Lan Luan; Colin T Sullender; Xue Li; Zhengtuo Zhao; Hanlin Zhu; Xiaoling Wei; Chong Xie; Andrew K Dunn Journal: J Neurosci Methods Date: 2017-12-05 Impact factor: 2.390
Authors: Steven M Wellman; Kelly Guzman; Kevin C Stieger; Lauren E Brink; Sadhana Sridhar; Mitchell T Dubaniewicz; Lehong Li; Franca Cambi; Takashi D Y Kozai Journal: Biomaterials Date: 2020-02-06 Impact factor: 12.479