<ol>
	<li>Maas, A. I. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Traumatic+brain+injury:+integrated+approaches+to+improve+prevention,+clinical+care,+and+research.">Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research.</a> The Lancet Neurology. 16 (12), 987-1048 (2017).</li><li>Taylor, C. A., Bell, J. M., Breiding, M. J., Xu, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Traumatic+Brain+Injury-Related+Emergency+Department+Visits,+Hospitalizations,+and+Deaths+-+United+States,+2007+and+2013.">Traumatic Brain Injury-Related Emergency Department Visits, Hospitalizations, and Deaths - United States, 2007 and 2013.</a> Morbidity and Mortality Weekly Report Surveillance Summaries. 66 (9), 1-16 (2007).</li><li>Pearn, M. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pathophysiology+Associated+with+Traumatic+Brain+Injury:+Current+Treatments+and+Potential+Novel+Therapeutics.">Pathophysiology Associated with Traumatic Brain Injury: Current Treatments and Potential Novel Therapeutics.</a> Cellular and Molecular Neurobiology. 37 (4), 571-585 (2017).</li><li>Nyanzu, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Improving+on+Laboratory+Traumatic+Brain+Injury+Models+to+Achieve+Better+Results.">Improving on Laboratory Traumatic Brain Injury Models to Achieve Better Results.</a> International Journal of Medical Sciences. 14 (5), 494-505 (2017).</li><li>Zhao, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Iron-induced+neuronal+damage+in+a+rat+model+of+post-traumatic+stress+disorder.">Iron-induced neuronal damage in a rat model of post-traumatic stress disorder.</a> Neuroscience. 330, 90-99 (2016).</li><li>Cepeda, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Contrecoup+Traumatic+Intracerebral+Hemorrhage:+A+Geometric+Study+of+the+Impact+Site+and+Association+with+Hemorrhagic+Progression.">Contrecoup Traumatic Intracerebral Hemorrhage: A Geometric Study of the Impact Site and Association with Hemorrhagic Progression.</a> Journal of Neurotrauma. 33 (11), 1034-1046 (2016).</li><li>Robicsek, S. A., Bhattacharya, A., Rabai, F., Shukla, K., Dore, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Blood-Related+Toxicity+after+Traumatic+Brain+Injury:+Potential+Targets+for+Neuroprotection.">Blood-Related Toxicity after Traumatic Brain Injury: Potential Targets for Neuroprotection.</a> Molecular Neurobiology. 57 (1), 159-178 (2020).</li><li>Morganti-Kossmann, M. C., Semple, B. D., Hellewell, S. C., Bye, N., Ziebell, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+complexity+of+neuroinflammation+consequent+to+traumatic+brain+injury:+from+research+evidence+to+potential+treatments.">The complexity of neuroinflammation consequent to traumatic brain injury: from research evidence to potential treatments.</a> Acta Neuropathologica. 137 (5), 731-755 (2019).</li><li>Ramlackhansingh, A. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inflammation+after+trauma:+microglial+activation+and+traumatic+brain+injury.">Inflammation after trauma: microglial activation and traumatic brain injury.</a> Annals of Neurology. 70 (3), 374-383 (2011).</li><li>Wang, G. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microglia/macrophage+polarization+dynamics+in+white+matter+after+traumatic+brain+injury.">Microglia/macrophage polarization dynamics in white matter after traumatic brain injury.</a> Journal of Cerebral Blood Flow &amp; Metabolism. 33 (12), 1864-1874 (2013).</li><li>Karve, I. P., Taylor, J. M., Crack, P. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+contribution+of+astrocytes+and+microglia+to+traumatic+brain+injury.">The contribution of astrocytes and microglia to traumatic brain injury.</a> British Journal of Pharmacology. 173 (4), 692-702 (2016).</li><li>Huber-Lang, M., Lambris, J. D., Ward, P. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Innate+immune+responses+to+trauma.">Innate immune responses to trauma.</a> Nature Immunology. 19 (4), 327-341 (2018).</li><li>Russo, M. V., McGavern, D. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inflammatory+neuroprotection+following+traumatic+brain+injury.">Inflammatory neuroprotection following traumatic brain injury.</a> Science. 353 (6301), 783-785 (2016).</li><li>Xiong, Y., Mahmood, A., Chopp, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+of+traumatic+brain+injury.">Animal models of traumatic brain injury.</a> Nature Reviews Neuroscience. 14 (2), 128-142 (2013).</li><li>Johnson, V. E., Meaney, D. F., Cullen, D. K., Smith, D. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+of+traumatic+brain+injury.">Animal models of traumatic brain injury.</a> Handbook of Clinical Neurology. 127, 115-128 (2015).</li><li>Albert-Weissenberger, C., Siren, A. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Experimental+traumatic+brain+injury.">Experimental traumatic brain injury.</a> Experimental &amp; Translational Stroke Medicine. 2 (1), 16 (2010).</li><li>Ma, X., Aravind, A., Pfister, B. J., Chandra, N., Haorah, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+Models+of+Traumatic+Brain+Injury+and+Assessment+of+Injury+Severity.">Animal Models of Traumatic Brain Injury and Assessment of Injury Severity.</a> Molecular Neurobiology. 56 (8), 5332-5345 (2019).</li><li>Osier, N. D., Korpon, J. R., Dixon, C. E., Kobeissy, F. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Brain+Neurotrauma:+Molecular,+Neuropsychological,+and+Rehabilitation+Aspects.">Brain Neurotrauma: Molecular, Neuropsychological, and Rehabilitation Aspects.</a> Frontiers in Neuroengineering. , (2015).</li><li>Osier, N. D., Dixon, C. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Controlled+Cortical+Impact+Model:+Applications,+Considerations+for+Researchers,+and+Future+Directions.">The Controlled Cortical Impact Model: Applications, Considerations for Researchers, and Future Directions.</a> Frontiers in Neurology. 7, 134 (2016).</li><li>Kramer, S. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Contribution+to+the+Theory+of+Cerebral+Concussion.">A Contribution to the Theory of Cerebral Concussion.</a> Annals of Surgery. 23 (2), 163-173 (1896).</li><li>King, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Brain+temperature+profiles+during+epidural+cooling+with+the+ChillerPad+in+a+monkey+model+of+traumatic+brain+injury.">Brain temperature profiles during epidural cooling with the ChillerPad in a monkey model of traumatic brain injury.</a> Journal of Neurotrauma. 27 (10), 1895-1903 (2010).</li><li>Costine, B. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuron-specific+enolase,+but+not+S100B+or+myelin+basic+protein,+increases+in+peripheral+blood+corresponding+to+lesion+volume+after+cortical+impact+in+piglets.">Neuron-specific enolase, but not S100B or myelin basic protein, increases in peripheral blood corresponding to lesion volume after cortical impact in piglets.</a> Journal of Neurotrauma. 29 (17), 2689-2695 (2012).</li><li>Anderson, R. W., Brown, C. J., Blumbergs, P. C., McLean, A. J., Jones, N. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impact+mechanics+and+axonal+injury+in+a+sheep+model.">Impact mechanics and axonal injury in a sheep model.</a> Journal of Neurotrauma. 20 (10), 961-974 (2003).</li><li>Chen, S., Pickard, J. D., Harris, N. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Time+course+of+cellular+pathology+after+controlled+cortical+impact+injury.">Time course of cellular pathology after controlled cortical impact injury.</a> Experimental Neurology. 182 (1), 87-102 (2003).</li><li>Lee, H. F., Lin, J. S., Chang, C. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Acute+Kahweol+Treatment+Attenuates+Traumatic+Brain+Injury+Neuroinflammation+and+Functional+Deficits.">Acute Kahweol Treatment Attenuates Traumatic Brain Injury Neuroinflammation and Functional Deficits.</a> Nutrients. 11 (10), 2301 (2019).</li><li>Dixon, C. E., Clifton, G. L., Lighthall, J. W., Yaghmai, A. A., Hayes, R. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+controlled+cortical+impact+model+of+traumatic+brain+injury+in+the+rat.">A controlled cortical impact model of traumatic brain injury in the rat.</a> Journal of Neuroscience Methods. 39 (3), 253-262 (1991).</li><li>Hung, T. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Deletion+or+inhibition+of+soluble+epoxide+hydrolase+protects+against+brain+damage+and+reduces+microglia-mediated+neuroinflammation+in+traumatic+brain+injury.">Deletion or inhibition of soluble epoxide hydrolase protects against brain damage and reduces microglia-mediated neuroinflammation in traumatic brain injury.</a> Oncotarget. 8 (61), 103236-103260 (2017).</li><li>Wu, C. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Post-injury+treatment+with+7,8-dihydroxyflavone,+a+TrkB+receptor+agonist,+protects+against+experimental+traumatic+brain+injury+via+PI3K/Akt+signaling.">Post-injury treatment with 7,8-dihydroxyflavone, a TrkB receptor agonist, protects against experimental traumatic brain injury via PI3K/Akt signaling.</a> PLoS One. 9 (11), 113397 (2014).</li><li>Chen, S. F., Su, W. S., Wu, C. H., Lan, T. H., Yang, F. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transcranial+Ultrasound+Stimulation+Improves+Long-Term+Functional+Outcomes+and+Protects+Against+Brain+Damage+in+Traumatic+Brain+Injury.">Transcranial Ultrasound Stimulation Improves Long-Term Functional Outcomes and Protects Against Brain Damage in Traumatic Brain Injury.</a> Molecular Neurobiology. 55 (8), 7079-7089 (2018).</li><li>Su, W. S., Wu, C. H., Chen, S. F., Yang, F. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Low-intensity+pulsed+ultrasound+improves+behavioral+and+histological+outcomes+after+experimental+traumatic+brain+injury.">Low-intensity pulsed ultrasound improves behavioral and histological outcomes after experimental traumatic brain injury.</a> Scientific Reports. 7 (1), 15524 (2017).</li><li>Chen, S. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Salidroside+improves+behavioral+and+histological+outcomes+and+reduces+apoptosis+via+PI3K/Akt+signaling+after+experimental+traumatic+brain+injury.">Salidroside improves behavioral and histological outcomes and reduces apoptosis via PI3K/Akt signaling after experimental traumatic brain injury.</a> PLoS One. 7 (9), 45763 (2012).</li><li>Chen, C. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Berberine+protects+against+neuronal+damage+via+suppression+of+glia-mediated+inflammation+in+traumatic+brain+injury.">Berberine protects against neuronal damage via suppression of glia-mediated inflammation in traumatic brain injury.</a> PLoS One. 9 (12), 115694 (2014).</li><li>Furmanski, O., Nieves, M. D., Doughty, M. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Controlled+Cortical+Impact+Model+of+Mouse+Brain+Injury+with+Therapeutic+Transplantation+of+Human+Induced+Pluripotent+Stem+Cell-Derived+Neural+Cells.">Controlled Cortical Impact Model of Mouse Brain Injury with Therapeutic Transplantation of Human Induced Pluripotent Stem Cell-Derived Neural Cells.</a> Journal of Visualized experiments. (149), e59561 (2019).</li><li>Romine, J., Gao, X., Chen, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Controlled+cortical+impact+model+for+traumatic+brain+injury.">Controlled cortical impact model for traumatic brain injury.</a> Journal of Visualized experiments. (90), e51781 (2014).</li><li>Saatman, K. E., Feeko, K. J., Pape, R. L., Raghupathi, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differential+behavioral+and+histopathological+responses+to+graded+cortical+impact+injury+in+mice.">Differential behavioral and histopathological responses to graded cortical impact injury in mice.</a> Journal of Neurotrauma. 23 (8), 1241-1253 (2006).</li><li>Robertson, C. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cerebral+glucose+metabolism+in+an+immature+rat+model+of+pediatric+traumatic+brain+injury.">Cerebral glucose metabolism in an immature rat model of pediatric traumatic brain injury.</a> Journal of Neurotrauma. 30 (24), 2066-2072 (2013).</li><li>Adelson, P. D., Fellows-Mayle, W., Kochanek, P. M., Dixon, C. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Morris+water+maze+function+and+histologic+characterization+of+two+age-at-injury+experimental+models+of+controlled+cortical+impact+in+the+immature+rat.">Morris water maze function and histologic characterization of two age-at-injury experimental models of controlled cortical impact in the immature rat.</a> Child's Nervous System. 29 (1), 43-53 (2013).</li></ol>

<table><tbody><tr><td>4mm Short Trephine Drill</td><td>Salvin Dental Specialties, Inc.</td><td>TREPH-SHORT-4</td><td></td></tr><tr><td>anti-Iba1 antibody</td><td>Wako chemicals</td><td>#019-19741</td><td></td></tr><tr><td>anti-Ly76 antibody</td><td>abcam</td><td>ab91113</td><td></td></tr><tr><td>carboxylate cement</td><td>3M</td><td>70201136010</td><td></td></tr><tr><td>cortical contusion injury impactor</td><td>Custom Design &amp;amp; Fabrication, Inc.</td><td>S/N 49-2004-C, eCCI Model 6.3</td><td>CCI device (S/N 49-2004-C, eCCI Model 6.3)</td></tr><tr><td>cresyl violet acetate</td><td>Sigma-Aldrich</td><td>C5042</td><td></td></tr><tr><td>DAB staining kit</td><td>Vector</td><td>SK-4105</td><td></td></tr><tr><td>goat anti-rabbit IgG secondary antibody, Alexa Fluor 488</td><td>Invitrogen</td><td>A11034</td><td></td></tr><tr><td>goat anti-rat IgG secondary antibody, Alexa Fluor 594</td><td>Invitrogen</td><td>A11007</td><td></td></tr><tr><td>Mayer&#039;s Hematoxylin</td><td>ScyTek</td><td>HMM500</td><td></td></tr><tr><td>tweezers</td><td>fine science tools</td><td>11252-20 NO. 5</td><td></td></tr><tr><td>isoflurane</td><td>Panion &amp;amp; BF Biotech Inc.</td><td></td><td></td></tr><tr><td>Bupivacaine 0.25%</td><td>Hospira</td><td></td><td></td></tr><tr><td>lithium carbonate</td><td>Sigma-Aldrich</td><td>62470</td><td></td></tr><tr><td>steriotexic frame</td><td>stoelting</td><td></td><td></td></tr><tr><td>scissors</td><td>fine science tools</td><td>14068-12</td><td></td></tr><tr><td>solvent blue 38</td><td>Sigma-Aldrich</td><td>S3382</td><td></td></tr></tbody></table>

a preclinical controlled cortical impact model for traumatic hemorrhage contusion and neuroinflammation

Watch this Scientific Journal Video about A Preclinical Controlled Cortical Impact Model for Traumatic Hemorrhage Contusion and Neuroinflammation at JoVE.com

<meta charset="utf8"></head><body>외상성 출혈 타박상 및 신경염증에 대한 전임상 제어 피질 영향 모델

외상성 출혈 타박상 및 신경염증에 대한 전임상 제어 피질 영향 모델

Cerebral contusion is a severe medical problem affecting millions of people worldwide each year. There is an urgent need to understand the ...

a-preclinical-controlled-cortical-impact-model-for-traumatic

Nanyang Technological University

Research

JoVE Journal

Medicine

A Preclinical Controlled Cortical Impact Model for Traumatic Hemorrhage Contusion and Neuroinflammation

1.8K 조회수.  Cheng Hsin General Hospital. 뇌타박상을 동반한 뇌골 출혈 및 신경 염증은 심각한 2차 뇌 손상을 유발할 수 있습니다. 이 프로토콜은 쥐 제어 피질 영향(CCI) 모델을 자세히 설명하여 연구원들이 출혈, 타박상 및 외상 후 면역 반응을 연구하고 잠재적인 치료법을 탐색할 수 있도록 합니다.

비디오: 외상성 출혈 타박상 및 신경염증에 대한 전임상 제어 피질 영향 모델

Controlled Cortical Impact Model of Mouse Brain Injury with Therapeutic Transplantation of Human Induced Pluripotent Stem Cell-Derived Neural Cells

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide. Disease pathology due to TBI progresses from the primary mechanical insult to secondary injury processes, including apoptosis and inflammation. Animal modeling has been valuable in the search to unravel injury mechanisms and evaluate potential neuroprotective therapies. This protocol describes the controlled cortical impact (CCI) model of focal, open-head TBI. Specifically, parameters for producing a mild unilateral cortical injury are described. Behavioral consequences of CCI are analyzed using the adhesive tape removal test of bilateral sensorimotor integration. Regarding experimental therapy for TBI pathology, this protocol also illustrates a process for transplanting cultured cells into the brain. Neural cell cultures derived from human induced pluripotent stem cells (hiPSCs) were chosen for their potential to show superior functional restoration in human TBI patients. Chronic survival of hiPSCs in the host mouse brain tissue is detected using a modified DAB immunohistochemical process.

This protocol demonstrates methodologies for a mouse model of open-skull traumatic brain injury and transplantation of cultured human induced pluripotent stem cell-derived cells into the injury site. Behavioral and histologic tests of outcomes from these procedures are also described in brief.

인간 유도 만능 줄기 세포 유래 신경 세포의 치료 이식으로 마우스 뇌 손상의 제어 피질 영향 모델

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide. Disease pathology due to TBI progresses from the primary mechanical ...

연구

발생학

Controlled Cortical Impact Model for Traumatic Brain Injury

Every year over a million Americans suffer a traumatic brain injury (TBI). Combined with the incidence of TBIs worldwide, the physical, emotional, social, and economical effects are staggering. Therefore, further research into the effects of TBI and effective treatments is necessary. The controlled cortical impact (CCI) model induces traumatic brain injuries ranging from mild to severe. This method uses a rigid impactor to deliver mechanical energy to an intact dura exposed following a craniectomy. Impact is made under precise parameters at a set velocity to achieve a pre-determined deformation depth. Although other TBI models, such as weight drop and fluid percussion, exist, CCI is more accurate, easier to control, and most importantly, produces traumatic brain injuries similar to those seen in humans. However, no TBI model is currently able to reproduce pathological changes identical to those seen in human patients. The CCI model allows investigation into the short-term and long-term effects of TBI, such as neuronal death, memory deficits, and cerebral edema, as well as potential therapeutic treatments for TBI.

Traumatic brain injuries (TBIs) remain a serious health problem. Using the controlled cortical impact surgery model, research on the effects of TBI and possible treatment methods may be performed.

외상성 뇌 손상에 대한 제어 피질 충격 모델

Every year over a million Americans suffer a traumatic brain injury (TBI).  Combined with the incidence of TBIs worldwide, the physical, emotional, ...

의학

A Novel and Translational Rat Model of Concussion Combining Force and Rotation with In Vivo Cerebral Microdialysis

Persistent cognitive and motor symptoms are known consequences of concussions/mild traumatic brain injury (mTBIs) that can be partly attributable to altered neurotransmission. Indeed, cerebral microdialysis studies in rodents have demonstrated an excessive extracellular glutamate release in the hippocampus within the first 10 min following trauma. Microdialysis offers the clear advantage of in vivo neurotransmitter continuous sampling while not having to sacrifice the animal. In addition to the aforementioned technique, a closed head injury model that exerts rapid acceleration and deceleration of the head and torso is needed, as such a factor is not available in many other animal models. The Wayne State weight-drop model mimics this essential component of human craniocerebral trauma, allowing the induction of an impact on the head of an unrestrained rodent with a falling weight. Our novel and translational rat model combines cerebral microdialysis with the Wayne State weight-drop model to study, in lightly anesthetized and unrestrained adult rats, the acute changes in extracellular neurotransmitter levels following concussion. In this protocol, the microdialysis probe was inserted inside the hippocampus as region of interest, and was left inserted in the brain at impact. There is a high density of terminals and receptors in the hippocampus, making it a relevant region to document altered neurotransmission following concussion. When applied to adult Sprague-Dawley rats, our combined model induced increases in hippocampal extracellular glutamate concentrations within the first 10 min, consistent with the previously reported post-concussion symptomology. This combined weight-drop model provides a reliable tool for researchers to study early therapeutic responses to concussions in addition to repetitive brain injury, since this protocol induces a closed-head mild trauma.

Neurotransmitter alteration is a mechanism of neural dysfunction that occurs after concussion and contributes to the sometimes-catastrophic long-term consequences. This rat model combines microdialysis, allowing in vivo neurotransmitter quantification, with a weight-drop technique exerting rapid acceleration and deceleration of the head and torso, an important factor of human craniocerebral trauma.

생체 뇌 미세 투석과 힘과 회전을 결합 하는 뇌진탕의 소설 및 번역 쥐 모델

Persistent cognitive and motor symptoms are known consequences of concussions/mild traumatic brain injury (mTBIs) that can be partly attributable to ...

신경과학

Murine Model of Controlled Cortical Impact for the Induction of Traumatic Brain Injury

The Centers for Disease Control and Injury Prevention estimate that almost 2 million people sustain a traumatic brain injury (TBI) every year in the United States. In fact, TBI is a contributing factor to over a third of all injury-related mortality. Nonetheless, the cellular and molecular mechanisms underlying the pathophysiology of TBI are poorly understood. Thus, preclinical models of TBI capable of replicating the injury mechanisms pertinent to TBI in human patients are a critical research need. The controlled cortical impact (CCI) model of TBI utilizes a mechanical device to directly impact the exposed cortex. While no model can full recapitulate the disparate injury patterns and heterogeneous nature of TBI in human patients, CCI is capable of inducing a wide range of clinically applicable TBI. Furthermore, CCI is easily standardized allowing investigators to compare results across experiments as well as across investigative groups. The following protocol is a detailed description of applying a severe CCI with a commercially available impacting device in a murine model of TBI.

Here we describe a protocol for the induction of murine traumatic brain injury via an open-head controlled cortical impact.

외상성 뇌 손상의 유도에 대한 제어 피질 영향의 뮤린 모델

The Centers for Disease Control and Injury Prevention estimate that almost 2 million people sustain a traumatic brain injury (TBI) every year in the ...

Low-intensity Blast Wave Model for Preclinical Assessment of Closed-head Mild Traumatic Brain Injury in Rodents

Traumatic brain injury (TBI) is a large-scale public health problem. Mild TBI is the most prevalent form of neurotrauma and accounts for a large number of medical visits in the United States. There are currently no FDA-approved treatments available for TBI. The increased incidence of military-related, blast-induced TBI further accentuates the urgent need for effective TBI treatments. Therefore, new preclinical TBI animal models that recapitulate aspects of human blast-related TBI will greatly advance the research efforts into the neurobiological and pathophysiological processes underlying mild to moderate TBI as well as the development of novel therapeutic strategies for TBI.
Here we present a reliable, reproducible model for the investigation of the molecular, cellular, and behavioral effects of mild to moderate blast-induced TBI. We describe a step-by-step protocol for closed-head, blast-induced mild TBI in rodents using a bench-top setup consisting of a gas-driven shock tube equipped with piezoelectric pressure sensors to ensure consistent test conditions. The benefits of the setup that we have established are its relative low-cost, ease of installation, ease of use and high-throughput capacity. Further advantages of this non-invasive TBI model include the scalability of the blast peak overpressure and the generation of controlled reproducible outcomes. The reproducibility and relevance of this TBI model has been evaluated in a number of downstream applications, including neurobiological, neuropathological, neurophysiological and behavioral analyses, supporting the use of this model for the characterization of processes underlying the etiology of mild to moderate TBI.

We present here a protocol of a blast wave model for rodents to investigate neurobiological and pathophysiological effects of mild to moderate traumatic brain injury. We established a gas-driven, bench-top setup equipped with pressure sensors allowing for reliable and reproducible generation of blast-induced mild to moderate traumatic brain injury.

설치류의 폐쇄 머리 경미한 외상성 뇌 손상의 전임상 평가를위한 저강도 폭발파 모델

Traumatic brain injury (TBI) is a large-scale public health problem. Mild TBI is the most prevalent form of neurotrauma and accounts for a large number of ...

Systems Analysis of the Neuroinflammatory and Hemodynamic Response to Traumatic Brain Injury

Mild traumatic brain injuries (mTBIs) are a significant public health problem. Repeated exposure to mTBI can lead to cumulative, long-lasting functional deficits. Numerous studies by our group and others have shown that mTBI stimulates cytokine expression and activates microglia, decreases cerebral blood flow and metabolism, and impairs cerebrovascular reactivity. Moreover, several works have reported an association between derangements in these neuroinflammatory and hemodynamic markers and cognitive impairments. Herein we detail methods to characterize the neuroinflammatory and hemodynamic tissue response to mTBI in mice. Specifically, we describe how to perform a weight-drop model of mTBI, how to longitudinally measure cerebral blood flow using a non-invasive optical technique called diffuse correlation spectroscopy, and how to perform a Luminex multiplexed immunoassay on brain tissue samples to quantify cytokines and immunomodulatory phospho-proteins (e.g., within the MAPK and NF&#954;B pathways) that respond to and regulate activity of microglia and other neural immune cells. Finally, we detail how to integrate these data using a multivariate systems analysis approach to understand the relationships between all of these variables. Understanding the relationships between these physiologic and molecular variables will ultimately enable us to identify mechanisms responsible for mTBI.

This protocol presents methods to characterize the neuroinflammatory and hemodynamic response to mild traumatic brain injury and to integrate these data as part of a multivariate systems analysis using partial least squares regression.

외상성 뇌 손상에 대한 신경 염증 및 혈역학 반응의 시스템 분석

Mild traumatic brain injuries (mTBIs) are a significant public health problem. Repeated exposure to mTBI can lead to cumulative, long-lasting functional ...

Electromagnetic Controlled Closed-Head Model of Mild Traumatic Brain Injury in Mice

Highly reproducible animal models of traumatic brain injury (TBI), with well-defined pathologies, are needed for testing therapeutic interventions and understanding the mechanisms of how a TBI alters brain function. The availability of multiple animal models of TBI is necessary to model the different aspects and severities of TBI seen in people. This manuscript describes the use of a midline closed head injury (CHI) to develop a mouse model of mild TBI. The model is considered mild because it does not produce structural brain lesions based on neuroimaging or gross neuronal loss. However, a single impact creates enough pathology that cognitive impairment is measurable at least 1 month after injury. A step-by-step protocol to induce a CHI in mice using a stereotaxically guided electromagnetic impactor is defined in the paper. The benefits of the mild midline CHI model include the reproducibility of the injury-induced changes with low mortality. The model has been temporally characterized up to 1 year after the injury for neuroimaging, neurochemical, neuropathological, and behavioral changes. The model is complementary to open skull models of controlled cortical impact using the same impactor device. Thus, labs can model both mild diffuse TBI and focal moderate-to-severe TBI with the same impactor.

The protocol describes mild traumatic brain injury in a mouse model. In particular, a step-by-step protocol to induce a mild midline closed head injury and the characterization of the animal model is fully explained.

생쥐의 경미한 외상성 뇌 손상에 대한 전자기 제어 폐쇄 머리 모델

Highly reproducible animal models of traumatic brain injury (TBI), with well-defined pathologies, are needed for testing therapeutic interventions and ...

Assessing Changes in Synaptic Plasticity Using an Awake Closed-Head Injury Model of Mild Traumatic Brain Injury

Mild traumatic brain injuries (mTBIs) are a prevalent health issue in North America. There is increasing pressure to utilize ecologically valid models of closed-head mTBI in the preclinical setting to increase translatability to the clinical population. The awake closed-headed injury (ACHI) model uses a modified controlled cortical impactor to deliver closed-headed injury, inducing clinically relevant behavioral deficits without the need for a craniotomy or the use of an anesthetic.
This technique does not normally induce fatalities, skull fractures, or brain bleeds, and is more consistent with being a mild injury. Indeed, the mild nature of the ACHI procedure makes it ideal for studies investigating repetitive mTBI (r-mTBI). Growing evidence indicates that r-mTBI can result in a cumulative injury that produces behavioral symptoms, neuropathological changes, and neurodegeneration. r-mTBI is common in youths playing sports, and these injuries occur during a period of robust synaptic reorganization and myelination, making the younger population particularly vulnerable to the long-term influences of r-mTBI.
Further, r-mTBI occurs in cases of intimate partner violence, a condition for which there are few objective screening measures. In these experiments, synaptic function was assessed in the hippocampus in juvenile rats that had experienced r-mTBI using the ACHI model. Following the injuries, a tissue slicer was utilized to make hippocampal slices to evaluate bidirectional synaptic plasticity in the hippocampus at either 1 or 7 days following the r-mTBI. Overall, the ACHI model provides researchers with an ecologically valid model to study changes in synaptic plasticity following mTBI and r-mTBI.

Here, it is demonstrated how an awake closed-head injury model can be used for examining the effects of repeated mild traumatic brain injury (r-mTBI) on synaptic plasticity in the hippocampus. The model replicates important features of r-mTBI in patients and is used in conjunction with in vitro electrophysiology.

경미한 외상성 뇌 손상의 깨어 있는 폐쇄 두부 손상 모델을 사용하여 시냅스 가소성의 변화 평가

Mild traumatic brain injuries (mTBIs) are a prevalent health issue in North America. There is increasing pressure to utilize ecologically valid models of ...

폐쇄형 머리 손상 방법을 통한 마우스의 rmTBI 유도

Modified Mouse Model of Repetitive Mild Traumatic Brain Injury Incorporating Thinned-Skull Window and Fluid Percussion

Mild traumatic brain injury is a clinically highly heterogeneous neurological disorder. Highly reproducible traumatic brain injury (TBI) animal models with well-defined pathologies are urgently needed for studying the mechanisms of neuropathology after mild TBI and testing therapeutics. Replicating the entire sequelae of TBI in animal models has proven to be a challenge. Therefore, the availability of multiple animal models of TBI is necessary to account for the diverse aspects and severities seen in TBI patients. CHI is one of the most common methods for fabricating rodent models of rmTBI. However, this method is susceptible to many factors, including the impact method used, the thickness and shape of the skull bone, animal apnea, and the type of head support and immobilization utilized. The aim of this protocol is to demonstrate a combination of the thinned-skull window and fluid percussion injury (FPI) methods to produce a precise mouse model of CHI-associated rmTBI. The primary objective of this protocol is to minimize factors that could impact the accuracy and consistency of CHI and FPI modeling, including skull bone thickness, shape, and head support. By utilizing a thinned-skull window method, potential inflammation due to craniotomy and FPI is minimized, resulting in an improved mouse model that replicates the clinical features observed in patients with mild TBI. Results from behavior and histological analysis using hematoxylin and eosin (HE) staining suggest that rmTBI can lead to a cumulative injury that produces changes in both behavior and gross morphology of the brain. Overall, the modified CHI-associated rmTBI presents a useful tool for researchers to explore the underlying mechanisms that contribute to focal and diffuse pathophysiological changes in rmTBI.

저자 스포트라이트: 반복적인 경미한 외상성 뇌 손상의 메커니즘 및 재활을 조사하기 위한 설치류 모델 최적화

This protocol presents a modified mouse model of repetitive mild traumatic brain injury (rmTBI) induced via a closed-head injury (CHI) method. The approach features a thinned-skull window and fluid percussion to reduce the inflammation commonly caused by meninges exposure, along with improved reproducibility and accuracy in modeling rmTBI in rodents.

얇아진 두개골 창과 유체 타악기를 통합한 반복적인 경미한 외상성 뇌 손상의 수정된 마우스 모델

Mild traumatic brain injury is a clinically highly heterogeneous neurological disorder. Highly reproducible traumatic brain injury (TBI) animal models ...

외상성 출혈 타박상 및 신경염증에 대한 전임상 제어 피질 영향 모델

요약

더 많은 비디오 탐색

이 비디오의 챕터

인간 유도 만능 줄기 세포 유래 신경 세포의 치료 이식으로 마우스 뇌 손상의 제어 피질 영향 모델

외상성 뇌 손상에 대한 제어 피질 충격 모델

생체 뇌 미세 투석과 힘과 회전을 결합 하는 뇌진탕의 소설 및 번역 쥐 모델

외상성 뇌 손상의 유도에 대한 제어 피질 영향의 뮤린 모델

설치류의 폐쇄 머리 경미한 외상성 뇌 손상의 전임상 평가를위한 저강도 폭발파 모델

외상성 뇌 손상에 대한 신경 염증 및 혈역학 반응의 시스템 분석

생쥐의 경미한 외상성 뇌 손상에 대한 전자기 제어 폐쇄 머리 모델

경미한 외상성 뇌 손상의 깨어 있는 폐쇄 두부 손상 모델을 사용하여 시냅스 가소성의 변화 평가

얇아진 두개골 창과 유체 타악기를 통합한 반복적인 경미한 외상성 뇌 손상의 수정된 마우스 모델

얇아진 두개골 창과 유체 타악기를 통합한 반복적인 경미한 외상성 뇌 손상의 수정된 마우스 모델