Cdk5 mediates rotational force-induced brain injury

Umfress, Alan; Chakraborti, Ayanabha; Priya Sudarsana Devi, Suma; Adams, Raegan; Epstein, Daniel; Massicano, Adriana; Sorace, Anna; Singh, Sarbjit; Iqbal Hossian, M.; Andrabi, Shaida A.; Crossman, David K.; Kumar, Nilesh; Shahid Mukhtar, M.; Luo, Huiyang; Simpson, Claire; Abell, Kathryn; Stokes, Matthew; Wiederhold, Thorsten; Rosen, Charles; Lu, Hongbing; Natarajan, Amarnath; Bibb, James A.

doi:10.1038/s41598-023-29322-4

Title: Cdk5 mediates rotational force-induced brain injury

Journal Article · 27 February 2023 · Scientific Reports

DOI: https://doi.org/10.1038/s41598-023-29322-4 · OSTI ID:1959378

Umfress, Alan; Chakraborti, Ayanabha; Priya Sudarsana Devi, Suma; Adams, Raegan; Epstein, Daniel; Massicano, Adriana; Sorace, Anna; Singh, Sarbjit; Iqbal Hossian, M.; Andrabi, Shaida A.; Crossman, David K.; Kumar, Nilesh; Shahid Mukhtar, M.; Luo, Huiyang; Simpson, Claire; Abell, Kathryn; Stokes, Matthew; Wiederhold, Thorsten; Rosen, Charles; Lu, Hongbing more »

Abstract Millions of traumatic brain injuries (TBIs) occur annually. TBIs commonly result from falls, traffic accidents, and sports-related injuries, all of which involve rotational acceleration/deceleration of the brain. During these injuries, the brain endures a multitude of primary insults including compression of brain tissue, damaged vasculature, and diffuse axonal injury. All of these deleterious effects can contribute to secondary brain ischemia, cellular death, and neuroinflammation that progress for weeks, months, and lifetime after injury. While the linear effects of head trauma have been extensively modeled, less is known about how rotational injuries mediate neuronal damage following injury. Here, we developed a new model of repetitive rotational head trauma in rodents and demonstrated acute and prolonged pathological, behavioral, and electrophysiological effects of rotational TBI (rTBI). We identify aberrant Cyclin-dependent kinase 5 (Cdk5) activity as a principal mediator of rTBI. We utilized Cdk5-enriched phosphoproteomics to uncover potential downstream mediators of rTBI and show pharmacological inhibition of Cdk5 reduces the cognitive and pathological consequences of injury. These studies contribute meaningfully to our understanding of the mechanisms of rTBI and how they may be effectively treated.

View Journal Article

Cite

Export

Save

Research Organization:: Univ. of Colorado, Boulder, CO (United States)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE; USDOE National Nuclear Security Administration (NNSA)

Grant/Contract Number:: NA0003962

OSTI ID:: 1959378

Journal Information:: Scientific Reports, Journal Name: Scientific Reports Journal Issue: 1 Vol. 13; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United Kingdom

Language:: English

References (113)

Mannitol for acute traumatic brain injury Wakai, Abel; McCabe, Aileen; Roberts, Ian Cochrane Database of Systematic Reviews https://doi.org/10.1002/14651858.CD001049.pub5	journal	August 2013
Diffuse axonal injury and traumatic coma in the primate Gennarelli, Thomas A.; Thibault, Lawrence E.; Adams, J. Hume Annals of Neurology, Vol. 12, Issue 6 https://doi.org/10.1002/ana.410120611	journal	December 1982
Neurobehavioral sequelae of traumatic brain injury Riggio, Silvana; Wong, Meredith Mount Sinai Journal of Medicine: A Journal of Translational and Personalized Medicine, Vol. 76, Issue 2 https://doi.org/10.1002/msj.20097	journal	April 2009
Pathophysiology of traumatic brain injury Greve, Mark W.; Zink, Brian J. Mount Sinai Journal of Medicine: A Journal of Translational and Personalized Medicine, Vol. 76, Issue 2 https://doi.org/10.1002/msj.20104	journal	April 2009
Comet: An open-source MS/MS sequence database search tool Eng, Jimmy K.; Jahan, Tahmina A.; Hoopmann, Michael R. PROTEOMICS, Vol. 13, Issue 1 https://doi.org/10.1002/pmic.201200439	journal	December 2012
Spectrin and calpain: a ‘target’ and a ‘sniper’ in the pathology of neuronal cells Czogalla, A.; Sikorski, A. F. Cellular and Molecular Life Sciences, Vol. 62, Issue 17 https://doi.org/10.1007/s00018-005-5097-0	journal	June 2005
Rotational Head Kinematics in Football Impacts: An Injury Risk Function for Concussion Rowson, Steven; Duma, Stefan M.; Beckwith, Jonathan G. Annals of Biomedical Engineering, Vol. 40, Issue 1 https://doi.org/10.1007/s10439-011-0392-4	journal	October 2011
Traumatic brain injury: neuropathological, neurocognitive and neurobehavioral sequelae Pavlovic, Dragan; Pekic, Sandra; Stojanovic, Marko Pituitary, Vol. 22, Issue 3 https://doi.org/10.1007/s11102-019-00957-9	journal	March 2019
Cognitive impairment following traumatic brain injury Arciniegas, David B.; Held, Kerri; Wagner, Peter Current Treatment Options in Neurology, Vol. 4, Issue 1 https://doi.org/10.1007/s11940-002-0004-6	journal	February 2002
Cdk5 Contributes to Huntington’s Disease Learning and Memory Deficits via Modulation of Brain Region-Specific Substrates Alvarez-Periel, Elena; Puigdellívol, Mar; Brito, Verónica Molecular Neurobiology, Vol. 55, Issue 8 https://doi.org/10.1007/s12035-017-0828-4	journal	December 2017
Decoding Hippocampal Signaling Deficits After Traumatic Brain Injury Atkins, Coleen M. Translational Stroke Research, Vol. 2, Issue 4 https://doi.org/10.1007/s12975-011-0123-z	journal	November 2011
CRASH-3: a win for patients with traumatic brain injury Cap, Andrew P. The Lancet, Vol. 394, Issue 10210 https://doi.org/10.1016/S0140-6736(19)32312-8	journal	November 2019
Aberrant Cdk5 Activation by p25 Triggers Pathological Events Leading to Neurodegeneration and Neurofibrillary Tangles Cruz, Jonathan C.; Tseng, Huang-Chun; Goldman, Joseph A. Neuron, Vol. 40, Issue 3 https://doi.org/10.1016/S0896-6273(03)00627-5	journal	October 2003
Tau pathology in Alzheimer disease and other tauopathies Iqbal, Khalid; del C. Alonso, Alejandra; Chen, She Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Vol. 1739, Issue 2-3 https://doi.org/10.1016/j.bbadis.2004.09.008	journal	January 2005
Cdk5, a therapeutic target for Alzheimer's disease? Tsai, Li-Huei; Lee, Ming-Sum; Cruz, Jonathan Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1697, Issue 1-2 https://doi.org/10.1016/j.bbapap.2003.11.019	journal	March 2004
Traumatic brain injury induces neuroinflammation and neuronal degeneration that is associated with escalated alcohol self-administration in rats Mayeux, Jacques P.; Teng, Sophie X.; Katz, Paige S. Behavioural Brain Research, Vol. 279 https://doi.org/10.1016/j.bbr.2014.10.053	journal	February 2015
Evaluation of early chronic functional outcomes and their relationship to pre-frontal cortex and hippocampal pathology following moderate-severe traumatic brain injury Arulsamy, Alina; Teng, Jason; Colton, Holly Behavioural Brain Research, Vol. 348 https://doi.org/10.1016/j.bbr.2018.04.009	journal	August 2018
Calpain inhibitor MDL 28170 protects hypoxic–ischemic brain injury in neonatal rats by inhibition of both apoptosis and necrosis Kawamura, Masanari; Nakajima, Wako; Ishida, Akira Brain Research, Vol. 1037, Issue 1-2 https://doi.org/10.1016/j.brainres.2004.12.050	journal	March 2005
The role of Cdk5 in cognition and neuropsychiatric and neurological pathology Barnett, David G. S.; Bibb, James A. Brain Research Bulletin, Vol. 85, Issue 1-2 https://doi.org/10.1016/j.brainresbull.2010.11.016	journal	April 2011
A Tissue-Specific Atlas of Mouse Protein Phosphorylation and Expression Huttlin, Edward L.; Jedrychowski, Mark P.; Elias, Joshua E. Cell, Vol. 143, Issue 7 https://doi.org/10.1016/j.cell.2010.12.001	journal	December 2010
Repopulating Microglia Promote Brain Repair in an IL-6-Dependent Manner Willis, Emily F.; MacDonald, Kelli P. A.; Nguyen, Quan H. Cell, Vol. 180, Issue 5 https://doi.org/10.1016/j.cell.2020.02.013	journal	March 2020
Regulation of NMDA receptor trafficking and gating by activity-dependent CaMKIIα phosphorylation of the GluN2A subunit Yong, Xuan Ling Hilary; Zhang, Lingrui; Yang, Liming Cell Reports, Vol. 36, Issue 1 https://doi.org/10.1016/j.celrep.2021.109338	journal	July 2021
Traumatic Brain Injury, Chronic Traumatic Encephalopathy, and Alzheimer Disease al-Dahhak, Roula; Khoury, Rita; Qazi, Erum Clinics in Geriatric Medicine, Vol. 34, Issue 4 https://doi.org/10.1016/j.cger.2018.06.008	journal	November 2018
Cyclin-dependent kinase-5 targeting for ischaemic stroke Slevin, Mark; Krupinski, Jerzy Current Opinion in Pharmacology, Vol. 9, Issue 2 https://doi.org/10.1016/j.coph.2008.10.003	journal	April 2009
Axonal pathology in traumatic brain injury Johnson, Victoria E.; Stewart, William; Smith, Douglas H. Experimental Neurology, Vol. 246 https://doi.org/10.1016/j.expneurol.2012.01.013	journal	August 2013
Treatment of traumatic brain injury with anti-inflammatory drugs Bergold, Peter J. Experimental Neurology, Vol. 275 https://doi.org/10.1016/j.expneurol.2015.05.024	journal	January 2016
Emerging pathogenic pathways in the spinocerebellar ataxias Carlson, Kerri M.; Andresen, J. Michael; Orr, Harry T. Current Opinion in Genetics & Development, Vol. 19, Issue 3 https://doi.org/10.1016/j.gde.2009.02.009	journal	June 2009
Traumatic Brain Injury Capizzi, Allison; Woo, Jean; Verduzco-Gutierrez, Monica Medical Clinics of North America, Vol. 104, Issue 2 https://doi.org/10.1016/j.mcna.2019.11.001	journal	March 2020
Neuroinflammation and brain atrophy in former NFL players: An in vivo multimodal imaging pilot study Coughlin, Jennifer M.; Wang, Yuchuan; Munro, Cynthia A. Neurobiology of Disease, Vol. 74 https://doi.org/10.1016/j.nbd.2014.10.019	journal	February 2015
EphB3 signaling propagates synaptic dysfunction in the traumatic injured brain Perez, Enmanuel J.; Cepero, Maria L.; Perez, Sebastian U. Neurobiology of Disease, Vol. 94 https://doi.org/10.1016/j.nbd.2016.06.007	journal	October 2016
The Neuropathology and Neurobiology of Traumatic Brain Injury Blennow, Kaj; Hardy, John; Zetterberg, Henrik Neuron, Vol. 76, Issue 5 https://doi.org/10.1016/j.neuron.2012.11.021	journal	December 2012
Calpain as a therapeutic target in traumatic brain injury Saatman, Kathryn E.; Creed, Jennifer; Raghupathi, Ramesh Neurotherapeutics, Vol. 7, Issue 1 https://doi.org/10.1016/j.nurt.2009.11.002	journal	January 2010
Cognitive Sequelae of Traumatic Brain Injury Rabinowitz, Amanda R.; Levin, Harvey S. Psychiatric Clinics of North America, Vol. 37, Issue 1 https://doi.org/10.1016/j.psc.2013.11.004	journal	March 2014
The Emerging Role of Cdk5 in Cancer Pozo, Karine; Bibb, James A. Trends in Cancer, Vol. 2, Issue 10 https://doi.org/10.1016/j.trecan.2016.09.001	journal	October 2016
Deregulation of Cdk5 in a Mouse Model of ALS Nguyen, Minh Dang; Larivière, Roxanne C.; Julien, Jean-Pierre Neuron, Vol. 30, Issue 1 https://doi.org/10.1016/s0896-6273(01)00268-9	journal	April 2001
ASPP Proteins Specifically Stimulate the Apoptotic Function of p53 Samuels-Lev, Yardena; O'Connor, Daniel J.; Bergamaschi, Daniele Molecular Cell, Vol. 8, Issue 4 https://doi.org/10.1016/s1097-2765(01)00367-7	journal	October 2001
Multiplexed Phosphoproteomic Profiling Using Titanium Dioxide and Immunoaffinity Enrichments Reveals Complementary Phosphorylation Events Possemato, Anthony P.; Paulo, Joao A.; Mulhern, Daniel Journal of Proteome Research, Vol. 16, Issue 4 https://doi.org/10.1021/acs.jproteome.6b00905	journal	February 2017
Neuropathological Effects of Chemotherapeutic Drugs Umfress, Alan; Speed, Haley E.; Tan, Chunfeng ACS Chemical Neuroscience, Vol. 12, Issue 16 https://doi.org/10.1021/acschemneuro.1c00338	journal	August 2021
Neurotoxicity induces cleavage of p35 to p25 by calpain Lee, Ming-sum; Kwon, Young T.; Li, Mingwei Nature, Vol. 405, Issue 6784 https://doi.org/10.1038/35012636	journal	May 2000
Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration Patrick, Gentry N.; Zukerberg, Lawrence; Nikolic, Margareta Nature, Vol. 402, Issue 6762 https://doi.org/10.1038/45159	journal	December 1999
The Role of Bradykinin B₁ and B₂ Receptors for Secondary Brain Damage after Traumatic Brain Injury in Mice Trabold, Raimund; Erös, Christian; Zweckberger, Klaus Journal of Cerebral Blood Flow & Metabolism, Vol. 30, Issue 1 https://doi.org/10.1038/jcbfm.2009.196	journal	September 2009
A probability-based approach for high-throughput protein phosphorylation analysis and site localization Beausoleil, Sean A.; Villén, Judit; Gerber, Scott A. Nature Biotechnology, Vol. 24, Issue 10 https://doi.org/10.1038/nbt1240	journal	September 2006
The role of ventral striatal cAMP signaling in stress-induced behaviors Plattner, Florian; Hayashi, Kanehiro; Hernández, Adan Nature Neuroscience, Vol. 18, Issue 8 https://doi.org/10.1038/nn.4066	journal	July 2015
Dissemination of brain inflammation in traumatic brain injury Shi, Kaibin; Zhang, Jianning; Dong, Jing-fei Cellular & Molecular Immunology, Vol. 16, Issue 6 https://doi.org/10.1038/s41423-019-0213-5	journal	March 2019
Meningeal lymphatic dysfunction exacerbates traumatic brain injury pathogenesis Bolte, Ashley C.; Dutta, Arun B.; Hurt, Mariah E. Nature Communications, Vol. 11, Issue 1 https://doi.org/10.1038/s41467-020-18113-4	journal	September 2020
Single-cell transcriptomic profiling of the aging mouse brain Ximerakis, Methodios; Lipnick, Scott L.; Innes, Brendan T. Nature Neuroscience, Vol. 22, Issue 10 https://doi.org/10.1038/s41593-019-0491-3	journal	September 2019
Mild traumatic brain injury induces memory deficits with alteration of gene expression profile Luo, Yawen; Zou, Haiyan; Wu, Yili Scientific Reports, Vol. 7, Issue 1 https://doi.org/10.1038/s41598-017-11458-9	journal	September 2017
modCHIMERA: a novel murine closed-head model of moderate traumatic brain injury Sauerbeck, A. D.; Fanizzi, C.; Kim, J. H. Scientific Reports, Vol. 8, Issue 1 https://doi.org/10.1038/s41598-018-25737-6	journal	May 2018
Large-scale phosphorylation analysis of mouse liver Villen, J.; Beausoleil, S. A.; Gerber, S. A. Proceedings of the National Academy of Sciences, Vol. 104, Issue 5 https://doi.org/10.1073/pnas.0609836104	journal	January 2007
Striatal dysregulation of Cdk5 alters locomotor responses to cocaine, motor learning, and dendritic morphology Meyer, Douglas A.; Richer, Edmond; Benkovic, Stanley A. Proceedings of the National Academy of Sciences, Vol. 105, Issue 47 https://doi.org/10.1073/pnas.0806078105	journal	November 2008
Phosphoprotein-based biomarkers as predictors for cancer therapy Carter, Angela M.; Tan, Chunfeng; Pozo, Karine Proceedings of the National Academy of Sciences, Vol. 117, Issue 31 https://doi.org/10.1073/pnas.2010103117	journal	July 2020
Calpain-dependent Proteolytic Cleavage of the p35 Cyclin-dependent Kinase 5 Activator to p25 Kusakawa, Gen-ichi; Saito, Taro; Onuki, Reiko Journal of Biological Chemistry, Vol. 275, Issue 22 https://doi.org/10.1074/jbc.M907757199	journal	June 2000
Prospective and declarative memory problems following moderate and severe traumatic brain injury Mathias, J. L.; Mansfield, K. M. Brain Injury, Vol. 19, Issue 4 https://doi.org/10.1080/02699050400005028	journal	April 2005
Preinjury Administration of the Calpain Inhibitor MDL-28170 Attenuates Traumatically Induced Axonal Injury Buki, A.; Farkas, O.; Doczi, T. Journal of Neurotrauma, Vol. 20, Issue 3 https://doi.org/10.1089/089771503321532842	journal	March 2003
The Pathobiology of Traumatically Induced Axonal Injury in Animals and Humans: A Review of Current Thoughts Povlishock, John T.; Christman, Carole W. Journal of Neurotrauma, Vol. 12, Issue 4 https://doi.org/10.1089/neu.1995.12.555	journal	August 1995
The Phosphorylated Axonal Form of the Neurofilament Subunit NF-H (pNF-H) as a Blood Biomarker of Traumatic Brain Injury Anderson, Kevin J.; Scheff, Stephen W.; Miller, Kelly M. Journal of Neurotrauma, Vol. 25, Issue 9 https://doi.org/10.1089/neu.2007.0488	journal	September 2008
Traumatic Brain Injury: A Disease Process, Not an Event Masel, Brent E.; DeWitt, Douglas S. Journal of Neurotrauma, Vol. 27, Issue 8 https://doi.org/10.1089/neu.2010.1358	journal	August 2010
Improving Understanding and Outcomes of Traumatic Brain Injury Using Bidirectional Translational Research Armstead, William M.; Vavilala, Monica S. Journal of Neurotrauma, Vol. 37, Issue 22 https://doi.org/10.1089/neu.2018.6119	journal	November 2020
Peptide TFP5/TP5 derived from Cdk5 activator P35 provides neuroprotection in the MPTP model of Parkinson’s disease Binukumar, Bk.; Shukla, Varsha; Amin, Niranjana D. Molecular Biology of the Cell, Vol. 26, Issue 24 https://doi.org/10.1091/mbc.E15-06-0415	journal	December 2015
Skyline: an open source document editor for creating and analyzing targeted proteomics experiments MacLean, Brendan; Tomazela, Daniela M.; Shulman, Nicholas Bioinformatics, Vol. 26, Issue 7 https://doi.org/10.1093/bioinformatics/btq054	journal	February 2010
Pathophysiology of traumatic brain injury Werner, C.; Engelhard, K. British Journal of Anaesthesia, Vol. 99, Issue 1 https://doi.org/10.1093/bja/aem131	journal	July 2007
Chronic traumatic encephalopathy neuropathology might not be inexorably progressive or unique to repetitive neurotrauma Iverson, Grant L.; Gardner, Andrew J.; Shultz, Sandy R. Brain, Vol. 142, Issue 12 https://doi.org/10.1093/brain/awz286	journal	October 2019
Overexpression of the Cdk5 inhibitory peptide in motor neurons rescue of amyotrophic lateral sclerosis phenotype in a mouse model Bk, Binukumar; Skuntz, Susan; Prochazkova, Michaela Human Molecular Genetics, Vol. 28, Issue 19 https://doi.org/10.1093/hmg/ddz118	journal	May 2019
Lewy Body Pathology and Chronic Traumatic Encephalopathy Associated With Contact Sports Adams, Jason W.; Alvarez, Victor E.; Mez, Jesse Journal of Neuropathology & Experimental Neurology, Vol. 77, Issue 9 https://doi.org/10.1093/jnen/nly065	journal	July 2018
Mechanisms of Traumatic Brain Injury: Biomechanical, Structural and Cellular Considerations Davis, Alice E. Critical Care Nursing Quarterly, Vol. 23, Issue 3 https://doi.org/10.1097/00002727-200011000-00002	journal	November 2000
Traumatic brain injury: physiology, mechanisms, and outcome Nortje, Jurgens; Menon, David K. Current Opinion in Neurology, Vol. 17, Issue 6 https://doi.org/10.1097/00019052-200412000-00011	journal	December 2004
Ferroptosis Contributes to Neuronal Death and Functional Outcome After Traumatic Brain Injury* Kenny, Elizabeth M.; Fidan, Emin; Yang, Qin Critical Care Medicine, Vol. 47, Issue 3 https://doi.org/10.1097/CCM.0000000000003555	journal	March 2019
Epidemiology of Adults Receiving Acute Inpatient Rehabilitation for a Primary Diagnosis of Traumatic Brain Injury in the United States Cuthbert, Jeffrey P.; Harrison-Felix, Cynthia; Corrigan, John D. Journal of Head Trauma Rehabilitation, Vol. 30, Issue 2 https://doi.org/10.1097/HTR.0000000000000012	journal	March 2015
Regional Neurodegeneration and Gliosis Are Amplified by Mild Traumatic Brain Injury Repeated at 24-Hour Intervals Bolton, Amanda N.; Saatman, Kathryn E. Journal of Neuropathology & Experimental Neurology, Vol. 73, Issue 10 https://doi.org/10.1097/NEN.0000000000000115	journal	October 2014
Phagocytic microglia and macrophages in brain injury and repair Yu, Fang; Wang, Yangfan; Stetler, Anne R. CNS Neuroscience & Therapeutics, Vol. 28, Issue 9 https://doi.org/10.1111/cns.13899	journal	June 2022
Organophosphates dysregulate dopamine signaling, glutamatergic neurotransmission, and induce neuronal injury markers in striatum Torres-Altoro, Melissa I.; Mathur, Brian N.; Drerup, Justin M. Journal of Neurochemistry, Vol. 119, Issue 2 https://doi.org/10.1111/j.1471-4159.2011.07428.x	journal	September 2011
Cell Death Mechanisms Following Traumatic Brain Injury Raghupathi, Ramesh Brain Pathology, Vol. 14, Issue 2 https://doi.org/10.1111/j.1750-3639.2004.tb00056.x	journal	April 2004
Involvement of aberrant cyclin-dependent kinase 5/p25 activity in experimental traumatic brain injury Yousuf, Mohammad A.; Tan, Chunfeng; Torres-Altoro, Melissa I. Journal of Neurochemistry, Vol. 138, Issue 2 https://doi.org/10.1111/jnc.13620	journal	May 2016
Linear and Angular Head Acceleration Measurements in Collegiate Football Rowson, Steven; Brolinson, Gunnar; Goforth, Mike Journal of Biomechanical Engineering, Vol. 131, Issue 6 https://doi.org/10.1115/1.3130454	journal	May 2009
Calpain-2 as a therapeutic target in repeated concussion–induced neuropathy and behavioral impairment Wang, Yubin; Liu, Yan; Nham, Amy Science Advances, Vol. 6, Issue 27 https://doi.org/10.1126/sciadv.aba5547	journal	July 2020
Chronic Traumatic Encephalopathy in Blast-Exposed Military Veterans and a Blast Neurotrauma Mouse Model Goldstein, Lee E.; Fisher, Andrew M.; Tagge, Chad A. Science Translational Medicine, Vol. 4, Issue 134 https://doi.org/10.1126/scitranslmed.3003716	journal	May 2012
Gross morphology and morphometric sequelae in the hippocampus, fornix, and corpus callosum of patients with severe non-missile traumatic brain injury without macroscopically detectable lesions: a T1 weighted MRI study Tomaiuolo, F. Journal of Neurology, Neurosurgery & Psychiatry, Vol. 75, Issue 9 https://doi.org/10.1136/jnnp.2003.017046	journal	September 2004
Large animal models of stroke and traumatic brain injury as translational tools Sorby-Adams, Annabel J.; Vink, Robert; Turner, Renée J. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Vol. 315, Issue 2 https://doi.org/10.1152/ajpregu.00163.2017	journal	August 2018
Biomechanics of neurotrauma Zhang, Liying; Yang, King H.; King, Albert I. Neurological Research, Vol. 23, Issue 2-3 https://doi.org/10.1179/016164101101198488	journal	March 2001
Chronic traumatic encephalopathy – neuropathology in athletes and war veterans Lakis, Nelli; Corona, Robert J.; Toshkezi, Gentian Neurological Research, Vol. 35, Issue 3 https://doi.org/10.1179/1743132813Y.0000000177	journal	April 2013
Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool Chen, Edward Y.; Tan, Christopher M.; Kou, Yan BMC Bioinformatics, Vol. 14, Issue 1 https://doi.org/10.1186/1471-2105-14-128	journal	January 2013
Merging pathology with biomechanics using CHIMERA (Closed-Head Impact Model of Engineered Rotational Acceleration): a novel, surgery-free model of traumatic brain injury Namjoshi, Dhananjay R.; Cheng, Wai; McInnes, Kurt A. Molecular Neurodegeneration, Vol. 9, Issue 1 https://doi.org/10.1186/1750-1326-9-55	journal	January 2014
Chronic traumatic encephalopathy: the dangers of getting "dinged" Lakhan, Shaheen E.; Kirchgessner, Annette SpringerPlus, Vol. 1, Issue 1 https://doi.org/10.1186/2193-1801-1-2	journal	March 2012
Antidepressants for depression after concussion and traumatic brain injury are still best practice Silverberg, Noah D.; Panenka, William J. BMC Psychiatry, Vol. 19, Issue 1 https://doi.org/10.1186/s12888-019-2076-9	journal	March 2019
Three decades of Cdk5 Pao, Ping-Chieh; Tsai, Li-Huei Journal of Biomedical Science, Vol. 28, Issue 1 https://doi.org/10.1186/s12929-021-00774-y	journal	November 2021
Combined [18F]DPA-714 micro-positron emission tomography and autoradiography imaging of microglia activation after closed head injury in mice Israel, Ina; Ohsiek, Andrea; Al-Momani, Ehab Journal of Neuroinflammation, Vol. 13, Issue 1 https://doi.org/10.1186/s12974-016-0604-9	journal	June 2016
Exposure to mild blast forces induces neuropathological effects, neurophysiological deficits and biochemical changes Hernandez, Adan; Tan, Chunfeng; Plattner, Florian Molecular Brain, Vol. 11, Issue 1 https://doi.org/10.1186/s13041-018-0408-1	journal	November 2018
Mild TBI and risk of Parkinson disease Gardner, Raquel C.; Byers, Amy L.; Barnes, Deborah E. Neurology, Vol. 90, Issue 20 https://doi.org/10.1212/WNL.0000000000005522	journal	April 2018
Documented head injury in early adulthood and risk of Alzheimer's disease and other dementias Plassman, B. L.; Havlik, R. J.; Steffens, D. C. Neurology, Vol. 55, Issue 8 https://doi.org/10.1212/wnl.55.8.1158	journal	October 2000
Concussion in Professional Football Viano, David C.; Hamberger, Anders; Bolouri, Hayde Neurosurgery, Vol. 64, Issue 6 https://doi.org/10.1227/01.NEU.0000345863.99099.C7	journal	June 2009
Measurement of head Impacts in Collegiate Football Players Mihalik, Jason P.; Bell, David R.; Marshall, Stephen W. Neurosurgery, Vol. 61, Issue 6 https://doi.org/10.1227/01.neu.0000306101.83882.c8	journal	December 2007
Measurement of head Impacts in Collegiate Football Players Guskiewicz, Kevin M.; Mihalik, Jason P.; Shankar, Viswanathan Neurosurgery, Vol. 61, Issue 6 https://doi.org/10.1227/01.neu.0000306103.68635.1a	journal	December 2007
The role of CDK5/P25 formation/inhibition in neurodegeneration Camins, A.; Verdaguer, E.; Folch, J. Drug News & Perspectives, Vol. 19, Issue 8 https://doi.org/10.1358/dnp.2006.19.8.1043961	journal	January 2006
Traumatic Brain Injury Causes Chronic Cortical Inflammation and Neuronal Dysfunction Mediated by Microglia Witcher, Kristina G.; Bray, Chelsea E.; Chunchai, Titikorn The Journal of Neuroscience, Vol. 41, Issue 7 https://doi.org/10.1523/JNEUROSCI.2469-20.2020	journal	January 2021
Chronic Cognitive Dysfunction after Traumatic Brain Injury Is Improved with a Phosphodiesterase 4B Inhibitor Titus, D. J.; Wilson, N. M.; Freund, J. E. Journal of Neuroscience, Vol. 36, Issue 27 https://doi.org/10.1523/JNEUROSCI.3212-15.2016	journal	July 2016
Ischemic Stroke Injury Is Mediated by Aberrant Cdk5 Meyer, D. A.; Torres-Altoro, M. I.; Tan, Z. Journal of Neuroscience, Vol. 34, Issue 24 https://doi.org/10.1523/JNEUROSCI.4368-13.2014	journal	June 2014
Pharmacology of Traumatic Brain Injury: Where Is the “Golden Bullet”? Beauchamp, Kathryn; Mutlak, Haitham; Smith, Wade R. Molecular Medicine, Vol. 14, Issue 11-12 https://doi.org/10.2119/2008-00050.Beauchamp	journal	November 2008
Cyclin-Dependent Kinase 5 (Cdk5): A Potential Therapeutic Target for the Treatment of Neurodegenerative Diseases and Diabetes Mellitus Wei, Fan-Yan; Tomizawa, Kazuhito Mini-Reviews in Medicinal Chemistry, Vol. 7, Issue 10 https://doi.org/10.2174/138955707782110114	journal	October 2007
Semi-quantitative Determination of Protein Expression Using Immunohistochemistry Staining and Analysis: An Integrated Protocol Crowe, Alexandra; Yue, Wei BIO-PROTOCOL, Vol. 9, Issue 24 https://doi.org/10.21769/BioProtoc.3465	journal	January 2019
Traumatic brain injury as a risk factor for Alzheimer's disease: current knowledge and future directions Dams-O'Connor, Kristen; Guetta, Gabrielle; Hahn-Ketter, Amanda E. Neurodegenerative Disease Management, Vol. 6, Issue 5 https://doi.org/10.2217/nmt-2016-0017	journal	October 2016
Cutting to the Pathophysiology Chase: Translating Cutting-Edge Neuroscience to Rehabilitation Practice in Sports-Related Concussion Management Chen, Yufen; Herrold, Amy A.; Gallagher, Virginia T. Journal of Orthopaedic & Sports Physical Therapy, Vol. 49, Issue 11 https://doi.org/10.2519/jospt.2019.8884	journal	November 2019
Why Most Traumatic Brain Injuries are Not Caused by Linear Acceleration but Skull Fractures are Kleiven, Svein Frontiers in Bioengineering and Biotechnology, Vol. 1 https://doi.org/10.3389/fbioe.2013.00015	journal	January 2013
Behavioral Outcomes Differ between Rotational Acceleration and Blast Mechanisms of Mild Traumatic Brain Injury Stemper, Brian D.; Shah, Alok S.; Budde, Matthew D. Frontiers in Neurology, Vol. 7 https://doi.org/10.3389/fneur.2016.00031	journal	March 2016
Role of Anticonvulsants in the Management of Posttraumatic Epilepsy Kirmani, Batool F.; Robinson, Diana Mungall; Fonkem, Ekokobe Frontiers in Neurology, Vol. 7 https://doi.org/10.3389/fneur.2016.00032	journal	March 2016
Methylphenidate Treatment of Cognitive Dysfunction in Adults After Mild to Moderate Traumatic Brain Injury: Rationale, Efficacy, and Neural Mechanisms Levin, Harvey; Troyanskaya, Maya; Petrie, JoAnn Frontiers in Neurology, Vol. 10 https://doi.org/10.3389/fneur.2019.00925	journal	September 2019
Recent Preclinical Insights Into the Treatment of Chronic Traumatic Encephalopathy Breen, Patrick W.; Krishnan, Vaishnav Frontiers in Neuroscience, Vol. 14 https://doi.org/10.3389/fnins.2020.00616	journal	July 2020
Oxytocin Receptor Signaling in Vascular Function and Stroke McKay, Erin C.; Counts, Scott E. Frontiers in Neuroscience, Vol. 14 https://doi.org/10.3389/fnins.2020.574499	journal	September 2020
Systemic Administration of a Brain Permeable Cdk5 Inhibitor Alters Neurobehavior Umfress, Alan; Singh, Sarbjit; Ryan, Kevin J. Frontiers in Pharmacology, Vol. 13 https://doi.org/10.3389/fphar.2022.863762	journal	May 2022
Neuroinflammation in Ischemic Stroke: Inhibition of cAMP-Specific Phosphodiesterases (PDEs) to the Rescue Ponsaerts, Laura; Alders, Lotte; Schepers, Melissa Biomedicines, Vol. 9, Issue 7 https://doi.org/10.3390/biomedicines9070703	journal	June 2021
Recent Developments in TSPO PET Imaging as A Biomarker of Neuroinflammation in Neurodegenerative Disorders Werry, Eryn L.; Bright, Fiona M.; Piguet, Olivier International Journal of Molecular Sciences, Vol. 20, Issue 13 https://doi.org/10.3390/ijms20133161	journal	June 2019
Calpain Inhibition Reduces Axolemmal Leakage in Traumatic Axonal Injury Czeiter, Endre; Büki, András; Bukovics, Péter Molecules, Vol. 14, Issue 12 https://doi.org/10.3390/molecules14125115	journal	December 2009
Revisiting Excitotoxicity in Traumatic Brain Injury: From Bench to Bedside Baracaldo-Santamaría, Daniela; Ariza-Salamanca, Daniel Felipe; Corrales-Hernández, María Gabriela Pharmaceutics, Vol. 14, Issue 1 https://doi.org/10.3390/pharmaceutics14010152	journal	January 2022
Complementary PTM Profiling of Drug Response in Human Gastric Carcinoma by Immunoaffinity and IMAC Methods with Total Proteome Analysis Stokes, Matthew; Farnsworth, Charles; Gu, Hongbo Proteomes, Vol. 3, Issue 3 https://doi.org/10.3390/proteomes3030160	journal	August 2015

Similar Records

Concussion, microvascular injury, and early tauopathy in young athletes after impact head injury and an impact concussion mouse model

Journal Article · 2018 · Brain · OSTI ID:1629042

Tagge, Chad A.; Fisher, Andrew M.; Minaeva, Olga V.; +43 more

Cineradiography System and Initial 3D-printed Brain Phantoms

Technical Report · 2021 · OSTI ID:1828674

LoDuca, Joe; Harke, Kathryn; Moya, Monica; +1 more

Progress Toward a Multiomic Understanding of Traumatic Brain Injury: A Review

Journal Article · 2022 · Biomarker Insights · OSTI ID:1995146

Kocheril, Philip Abraham; Moore, Shepard Christian; Lenz, Kiersten Danielle; +2 more

Related Subjects

60 APPLIED LIFE SCIENCES
Science & Technology - Other Topics

Title: Cdk5 mediates rotational force-induced brain injury

Citation Formats

References (113)

Similar Records

Related Subjects