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Traumatic brain injury causes long-term behavioral changes related to region-specific increases of cerebral blood flow

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Abstract

Traumatic brain injury (TBI) is a leading cause of disability and death and survivors often suffer from long-lasting motor impairment, cognitive deficits, anxiety disorders and epilepsy. Few experimental studies have investigated long-term sequelae after TBI and relations between behavioral changes and neural activity patterns remain elusive. We examined these issues in a murine model of TBI combining histology, behavioral analyses and single-photon emission computed tomography (SPECT) imaging of regional cerebral blood flow (CBF) as a proxy for neural activity. Adult C57Bl/6N mice were subjected to unilateral cortical impact injury and investigated at early (15–57 days after lesion, dal) and late (184–225 dal) post-traumatic time points. TBI caused pronounced tissue loss of the parietal cortex and subcortical structures and enduring neurological deficits. Marked perilesional astro- and microgliosis was found at 57 dal and declined at 225 dal. Motor and gait pattern deficits occurred at early time points after TBI and improved over the time. In contrast, impaired performance in the Morris water maze test and decreased anxiety-like behavior persisted together with an increased susceptibility to pentylenetetrazole-induced seizures suggesting alterations in neural activity patterns. Accordingly, SPECT imaging of CBF indicated asymmetric hemispheric baseline neural activity patterns. In the ipsilateral hemisphere, increased baseline neural activity was found in the amygdala. In the contralateral hemisphere, homotopic to the structural brain damage, the hippocampus and distinct cortex regions displayed increased baseline neural activity. Thus, regionally elevated CBF along with behavioral alterations indicate that increased neural activity is critically involved in the long-lasting consequences of TBI.

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References

  • Acosta SA, Tajiri N, Shinozuka K, Ishikawa H, Grimmig B, Diamond DM, Sanberg PR, Bickford PC, Kaneko Y, Borlongan CV (2013) Long-term upregulation of inflammation and suppression of cell proliferation in the brain of adult rats exposed to traumatic brain injury using the controlled cortical impact model. PLoS One 8:3

    Article  Google Scholar 

  • Almeida-Suhett CP, Prager EM, Pidoplichko V, Figueiredo TH, Marini AM, Li Z, Eiden LE, Braga MFM (2014) Reduced GABAergic inhibition in the basolateral amygdala and the development of anxiety-like behaviors after mild traumatic brain injury. PLoS One 9:e102627

    Article  PubMed  PubMed Central  Google Scholar 

  • Axelson HW, Winkler T, Flygt J, Djupsjo A, Hanell A, Marklund N (2013) Plasticity of the contralateral motor cortex following focal traumatic brain injury in the rat. Restor Neurol Neurosci 31:73–85

    PubMed  Google Scholar 

  • Bhattacharya S, Herrera-Molina R, Sabanov V, Ahmed T, Iscru E, Stober F, Richter K, Fischer KD, Angenstein F, Goldschmidt J, Beesley PW, Balschun D, Smalla KH, Gundelfinger ED, Montag D (2017) Genetically induced retrograde amnesia of associative memories after neuroplastin ablation. Biol Psychiatry 81:124–135

    Article  CAS  PubMed  Google Scholar 

  • Bolkvadze T, Pitkanen A (2012) Development of post-traumatic epilepsy after controlled cortical impact and lateral fluid-percussion-induced brain injury in the mouse. J Neurotrauma 29:789–812

    Article  PubMed  Google Scholar 

  • Bramlett HM, Dietrich WD (2007) Progressive damage after brain and spinal cord injury: pathomechanisms and treatment strategies. Prog Brain Res 161:125–141

    Article  PubMed  Google Scholar 

  • Burda JE, Bernstein AM, Sofroniew MV (2016) Astrocyte roles in traumatic brain injury. Exp Neurol 275(Pt 3):305–315

    Article  CAS  PubMed  Google Scholar 

  • Cantu D, Walker K, Andresen L, Taylor-Weiner A, Hampton D, Tesco G, Dulla CG (2015) Traumatic brain injury increases cortical glutamate network activity by compromising GABAergic control. Cereb Cortex 25:2306–2320

    Article  PubMed  Google Scholar 

  • Chauhan NB (2014) Chronic neurodegenerative consequences of traumatic brain injury. Restor Neurol Neurosci 32:337–365

    CAS  PubMed  Google Scholar 

  • Cole JH, Leech R, Sharp DJ (2015) Prediction of brain age suggests accelerated atrophy after traumatic brain injury. Ann Neurol 77:571–581

    Article  PubMed  PubMed Central  Google Scholar 

  • Collins R, Pastorek N, Tharp A, Kent T (2012) Behavioral and psychiatric comorbidities of TBI. In: Tsao JW (ed) Traumatic brain injury. Springer, New York, pp 223–244

    Chapter  Google Scholar 

  • Corps KN, Roth TL, McGavern DB (2015) Inflammation and neuroprotection in traumatic brain injury. JAMA Neurol 72:355–362

    Article  PubMed  PubMed Central  Google Scholar 

  • Dixon CE, Kochanek PM, Yan HQ, Schiding JK, Griffith RG, Baum E, Marion DW, DeKosky ST (1999) One-year study of spatial memory performance, brain morphology, and cholinergic markers after moderate controlled cortical impact in rats. J Neurotrauma 16:109–122

    Article  CAS  PubMed  Google Scholar 

  • Endepols H, Sommer S, Backes H, Wiedermann D, Graf R, Hauber W (2010) Effort-based decision making in the rat: an [18F] fluorodeoxyglucose micro positron emission tomography study. J Neurosci 30:9708–9714

    Article  CAS  PubMed  Google Scholar 

  • Erturk A, Mentz S, Stout EE, Hedehus M, Dominguez SL, Neumaier L, Krammer F, Llovera G, Srinivasan K, Hansen DV, Liesz A, Scearce-Levie KA, Sheng M (2016) Interfering with the chronic immune response rescues chronic degeneration after traumatic brain injury. J Neurosci 36:9962–9975

    Article  PubMed  Google Scholar 

  • Ferraro TN, Golden GT, Smith GG, Jean PS, Schork NJ, Mulholland N, Ballas C, Schill J, Buono RJ, Berrettini WH (1999) Mapping loci for pentylenetetrazol-induced seizure susceptibility in mice. J Neurosci 19:6733–6739

    CAS  PubMed  Google Scholar 

  • Gavett B, Stern R, Cantu R, Nowinski C, McKee A (2010) Mild traumatic brain injury: a risk factor for neurodegeneration. Alzheimer’s Res Ther 2:18

    Article  Google Scholar 

  • Gold EM, Su D, López-Velázquez L, Haus DL, Perez H, Lacuesta GA, Anderson AJ, Cummings BJ (2013) Functional assessment of long-term deficits in rodent models of traumatic brain injury. Regen Med 8:483–516

    Article  CAS  PubMed  Google Scholar 

  • Goldschmidt J, Wanger T, Engelhorn A, Friedrich H, Happel M, Ilango A, Engelmann M, Stuermer IW, Ohl FW, Scheich H (2010) High-resolution mapping of neuronal activity using the lipophilic thallium chelate complex TlDDC: protocol and validation of the method. Neuroimage 49:303–315

    Article  CAS  PubMed  Google Scholar 

  • Gyoneva S, Ransohoff RM (2015) Inflammatory reaction after traumatic brain injury: therapeutic potential of targeting cell-cell communication by chemokines. Trends Pharmacol Sci 36:471–480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harish G, Mahadevan A, Pruthi N, Sreenivasamurthy SK, Puttamallesh VN, Keshava Prasad TS, Shankar SK, Srinivas Bharath MM (2015) Characterization of traumatic brain injury in human brains reveals distinct cellular and molecular changes in contusion and pericontusion. J Neurochem 134:156–172

    Article  CAS  PubMed  Google Scholar 

  • Harris NG, Verley DR, Gutman BA, Thompson PM, Yeh HJ, Brown JA (2016) Disconnection and hyper-connectivity underlie reorganization after TBI: a rodent functional connectomic analysis. Exp Neurol 277:124–138

    Article  CAS  PubMed  Google Scholar 

  • Hennig J, Nauerth A, Friedburg H (1986) RARE imaging: a fast imaging method for clinical MR. Magn Reson Med 3:823–833

    Article  CAS  PubMed  Google Scholar 

  • Huang C, Sakry D, Menzel L, Dangel L, Sebastiani A, Kramer T, Karram K, Engelhard K, Trotter J, Schafer MK (2016) Lack of NG2 exacerbates neurological outcome and modulates glial responses after traumatic brain injury. Glia 64:507–523

    Article  PubMed  Google Scholar 

  • Hunt RF, Scheff SW, Smith BN (2010) Regionally localized recurrent excitation in the dentate gyrus of a cortical contusion model of posttraumatic epilepsy. J Neurophysiol 103:1490–1500

    Article  PubMed  PubMed Central  Google Scholar 

  • Hunt RF, Boychuk JA, Smith BN (2013) Neural circuit mechanisms of post-traumatic epilepsy. Front Cell Neurosci 7:89

    Article  PubMed  PubMed Central  Google Scholar 

  • Johnk K, Kuhtz-Buschbeck JP, Stolze H, Serocki G, Kalwa S, Ritz A, Benz B, Illert M (1999) Assessment of sensorimotor functions after traumatic brain injury (TBI) in childhood—methodological aspects. Restor Neurol Neurosci 14:143–152

    CAS  Google Scholar 

  • Johnson VE, Stewart JE, Begbie FD, Trojanowski JQ, Smith DH, Stewart W (2013) Inflammation and white matter degeneration persist for years after a single traumatic brain injury. Brain 136:28–42

    Article  PubMed  PubMed Central  Google Scholar 

  • Jones TA, Kleim JA, Greenough WT (1996) Synaptogenesis and dendritic growth in the cortex opposite unilateral sensorimotor cortex damage in adult rats: a quantitative electron microscopic examination. Brain Res 733:142–148

    Article  CAS  PubMed  Google Scholar 

  • Jones NC, Cardamone L, Williams JP, Salzberg MR, Myers D, O’Brien TJ (2008) Experimental traumatic brain injury induces a pervasive hyperanxious phenotype in rats. J Neurotrauma 25:1367–1374

    Article  PubMed  Google Scholar 

  • Jorge RE, Arciniegas DB (2014) Mood disorders after TBI. Psychiatr Clin North Am 37:13–29

    Article  PubMed  PubMed Central  Google Scholar 

  • Karve IP, Taylor JM, Crack PJ (2016) The contribution of astrocytes and microglia to traumatic brain injury. Br J Pharmacol 173:692–702

    Article  CAS  PubMed  Google Scholar 

  • Kochanek PM, Hendrich KS, Dixon CE, Schiding JK, Williams DS, Ho C (2002) Cerebral blood flow at one year after controlled cortical impact in rats: assessment by magnetic resonance imaging. J Neurotrauma 19:1029–1037

    Article  PubMed  Google Scholar 

  • Kolodziej A, Lippert M, Angenstein F, Neubert J, Pethe A, Grosser OS, Amthauer H, Schroeder UH, Reymann KG, Scheich H, Ohl FW, Goldschmidt J (2014) SPECT-imaging of activity-dependent changes in regional cerebral blood flow induced by electrical and optogenetic self-stimulation in mice. Neuroimage 103:171–180

    Article  PubMed  Google Scholar 

  • Kozlowski DA, Schallert T (1998) Relationship between dendritic pruning and behavioral recovery following sensorimotor cortex lesions. Behav Brain Res 97:89–98

    Article  CAS  PubMed  Google Scholar 

  • Laitinen T, Sierra A, Bolkvadze T, Pitkanen A, Grohn O (2015) Diffusion tensor imaging detects chronic microstructural changes in white and gray matter after traumatic brain injury in rat. Front Neurosci 9:128

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee S, Park J-Y, Lee W-H, Kim H, Park H-C, Mori K, Suk K (2009) Lipocalin-2 is an autocrine mediator of reactive astrocytosis. J Neurosci 29:234–249

    Article  CAS  PubMed  Google Scholar 

  • Lindner MD, Plone MA, Cain CK, Frydel B, Francis JM, Emerich DF, Sutton RL (1998) Dissociable long-term cognitive deficits after frontal versus sensorimotor cortical contusions. J Neurotrauma 15:199–216

    Article  CAS  PubMed  Google Scholar 

  • Loane DJ, Byrnes KR (2010) Role of microglia in neurotrauma. Neurotherapeutics 7:366–377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Loane DJ, Kumar A, Stoica BA, Cabatbat R, Faden AI (2014) Progressive neurodegeneration after experimental brain trauma: association with chronic microglial activation. J Neuropathol Exp Neurol 73:14–29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luh C, Gierth K, Timaru-Kast R, Engelhard K, Werner C, Thal SC (2011) Influence of a brief episode of anesthesia during the induction of experimental brain trauma on secondary brain damage and inflammation. PLoS One 6:19

    Article  Google Scholar 

  • Ma Y, Hof PR, Grant SC, Blackband SJ, Bennett R, Slatest L, McGuigan MD, Benveniste H (2005) A three-dimensional digital atlas database of the adult C57BL/6J mouse brain by magnetic resonance microscopy. Neuroscience 135:1203–1215

    Article  CAS  PubMed  Google Scholar 

  • Marklund N, Hillered L (2011) Animal modelling of traumatic brain injury in preclinical drug development: where do we go from here? Br J Pharmacol 164:1207–1229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McConeghy KW, Hatton J, Hughes L, Cook AM (2012) A review of neuroprotection pharmacology and therapies in patients with acute traumatic brain injury. CNS Drugs 26:613–636

    Article  CAS  PubMed  Google Scholar 

  • Menzel L, Paterka M, Bittner S, White R, Bobkiewicz W, van Horssen J, Schachner M, Witsch E, Kuhlmann T, Zipp F, Schafer MK (2016) Down-regulation of neuronal L1 cell adhesion molecule expression alleviates inflammatory neuronal injury. Acta Neuropathol 132:703–720

    Article  CAS  PubMed  Google Scholar 

  • Menzel L, Kleber L, Friedrich C, Hummel R, Dangel L, Winter J, Schmitz K, Tegeder I, Schafer MK (2017) Progranulin protects against exaggerated axonal injury and astrogliosis following traumatic brain injury. Glia 65:278–292

    Article  PubMed  Google Scholar 

  • Mishra AM, Bai X, Sanganahalli BG, Waxman SG, Shatillo O, Grohn O, Hyder F, Pitkanen A, Blumenfeld H (2014) Decreased resting functional connectivity after traumatic brain injury in the rat. PLoS One 9:e95280

    Article  PubMed  PubMed Central  Google Scholar 

  • Mukherjee S, Zeitouni S, Cavarsan CF, Shapiro LA (2013) Increased seizure susceptibility in mice 30 days after fluid percussion injury. Front Neurol 4:28

    Article  PubMed  PubMed Central  Google Scholar 

  • Neumann M, Wang Y, Kim S, Hong SM, Jeng L, Bilgen M, Liu J (2009) Assessing gait impairment following experimental traumatic brain injury in mice. J Neurosci Methods 176:34–44

    Article  PubMed  Google Scholar 

  • Nissinen J, Halonen T, Koivisto E, Pitkanen A (2000) A new model of chronic temporal lobe epilepsy induced by electrical stimulation of the amygdala in rat. Epilepsy Res 38:177–205

    Article  CAS  PubMed  Google Scholar 

  • Ochi F, Esquenazi A, Hirai B, Talaty M (1999) Temporal-spatial feature of gait after traumatic brain injury. J Head Trauma Rehabil 14:105–115

    Article  CAS  PubMed  Google Scholar 

  • Osier ND, Carlson SW, DeSana A, Dixon CE (2015) Chronic histopathological and behavioral outcomes of experimental traumatic brain injury in adult male animals. J Neurotrauma 32:1861–1882

    Article  PubMed  PubMed Central  Google Scholar 

  • Palmer LM, Schulz JM, Murphy SC, Ledergerber D, Murayama M, Larkum ME (2012) The cellular basis of GABA(B)-mediated interhemispheric inhibition. Science 335:989–993

    Article  CAS  PubMed  Google Scholar 

  • Palmer CP, Metheny HE, Elkind JA, Cohen AS (2016) Diminished amygdala activation and behavioral threat response following traumatic brain injury. Exp Neurol 277:215–226

    Article  PubMed  PubMed Central  Google Scholar 

  • Peterson TC, Maass WR, Anderson JR, Anderson GD, Hoane MR (2015) A behavioral and histological comparison of fluid percussion injury and controlled cortical impact injury to the rat sensorimotor cortex. Behav Brain Res 294:254–263

    Article  PubMed  PubMed Central  Google Scholar 

  • Phillips RG, LeDoux JE (1992) Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behav Neurosci 106:274–285

    Article  CAS  PubMed  Google Scholar 

  • Pierce JE, Smith DH, Trojanowski JQ, McIntosh TK (1998) Enduring cognitive, neurobehavioral and histopathological changes persist for up to one year following severe experimental brain injury in rats. Neuroscience 87:359–369

    Article  CAS  PubMed  Google Scholar 

  • Pitkanen A, Kemppainen S, Ndode-Ekane XE, Huusko N, Huttunen JK, Grohn O, Immonen R, Sierra A, Bolkvadze T (2014) Posttraumatic epilepsy—disease or comorbidity? Epilepsy Behav 38:19–24

    Article  PubMed  Google Scholar 

  • Ramlackhansingh AF, Brooks DJ, Greenwood RJ, Bose SK, Turkheimer FE, Kinnunen KM, Gentleman S, Heckemann RA, Gunanayagam K, Gelosa G, Sharp DJ (2011) Inflammation after trauma: microglial activation and traumatic brain injury. Ann Neurol 70:374–383

    Article  PubMed  Google Scholar 

  • Ratcliff G, Colantonio A, Escobar M, Chase S, Vernich L (2005) Long-term survival following traumatic brain injury. Disabil Rehabil 27:305–314

    Article  PubMed  Google Scholar 

  • Reger ML, Poulos AM, Buen F, Giza CC, Hovda DA, Fanselow MS (2012) Concussive brain injury enhances fear learning and excitatory processes in the amygdala. Biol Psychiatry 71:335–343

    Article  PubMed  Google Scholar 

  • Roozenbeek B, Maas AIR, Menon DK (2013) Changing patterns in the epidemiology of traumatic brain injury. Nat Rev Neurol 9:231–236

    Article  PubMed  Google Scholar 

  • Sashindranath M, Daglas M, Medcalf RL (2015) Evaluation of gait impairment in mice subjected to craniotomy and traumatic brain injury. Behav Brain Res 286:33–38

    Article  CAS  PubMed  Google Scholar 

  • Schaible E-V, Windschügl J, Bobkiewicz W, Kaburov Y, Dangel L, Krämer T, Huang C, Sebastiani A, Luh C, Werner C, Engelhard K, Thal SC, Schäfer MKE (2014) 2-Methoxyestradiol confers neuroprotection and inhibits a maladaptive HIF-1α response after traumatic brain injury in mice. J Neurochem 129:940–954

    Article  CAS  PubMed  Google Scholar 

  • Shively SB, Horkayne-Szakaly I, Jones RV, Kelly JP, Armstrong RC, Perl DP (2016) Characterisation of interface astroglial scarring in the human brain after blast exposure: a post-mortem case series. Lancet Neurol 9:944–953

    Article  Google Scholar 

  • Sierra A, Laitinen T, Grohn O, Pitkanen A (2015) Diffusion tensor imaging of hippocampal network plasticity. Brain Struct Funct 220:781–801

    Article  PubMed  Google Scholar 

  • Soblosky JS, Matthews MA, Davidson JF, Tabor SL, Carey ME (1996) Traumatic brain injury of the forelimb and hindlimb sensorimotor areas in the rat: physiological, histological and behavioral correlates. Behav Brain Res 79:79–92

    Article  CAS  PubMed  Google Scholar 

  • Takeuchi N, Ikoma K, Chuma T, Matsuo Y (2006) Measurement of transcallosal inhibition in traumatic brain injury by transcranial magnetic stimulation. Brain Inj 20:991–996

    Article  PubMed  Google Scholar 

  • Thanos PK, Robison L, Nestler EJ, Kim R, Michaelides M, Lobo MK, Volkow ND (2013) Mapping brain metabolic connectivity in awake rats with muPET and optogenetic stimulation. J Neurosci 33:6343–6349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Timaru-Kast R, Luh C, Gotthardt P, Huang C, Schäfer MK, Engelhard K, Thal SC (2012) Influence of age on brain edema formation, secondary brain damage and inflammatory response after brain trauma in mice. PLoS One 7:e43829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Titianova EB, Peurala SH, Pitkanen K, Tarkka IM (2008) Gait reveals bilateral adaptation of motor control in patients with chronic unilateral stroke. Aging Clin Exp Res 20:131–138

    Article  PubMed  Google Scholar 

  • Tsenter J, Beni-Adani L, Assaf Y, Alexandrovich AG, Trembovler V, Shohami E (2008) Dynamic changes in the recovery after traumatic brain injury in mice: effect of injury severity on T2-weighted MRI abnormalities, and motor and cognitive functions. J Neurotrauma 25:324–333

    Article  PubMed  Google Scholar 

  • Velazquez A, Ortega M, Rojas S, Gonzalez-Olivan FJ, Rodriguez-Baeza A (2015) Widespread microglial activation in patients deceased from traumatic brain injury. Brain Inj 29:1126–1133

    Article  PubMed  Google Scholar 

  • Villapol S, Byrnes KR, Symes AJ (2014) Temporal dynamics of cerebral blood flow, cortical damage, apoptosis, astrocyte-vasculature interaction and astrogliosis in the pericontusional region after traumatic brain injury. Front Neurol 5:82

    Article  PubMed  PubMed Central  Google Scholar 

  • Walker WC, Pickett TC (2007) Motor impairment after severe traumatic brain injury: a longitudinal multicenter study. J Rehabil Res Dev 44:975–982

    Article  PubMed  Google Scholar 

  • Washington PM, Forcelli PA, Wilkins T, Zapple DN, Parsadanian M, Burns MP (2012) The effect of injury severity on behavior: a phenotypic study of cognitive and emotional deficits after mild, moderate, and severe controlled cortical impact injury in mice. J Neurotrauma 29:2283–2296

    Article  PubMed  PubMed Central  Google Scholar 

  • Wyckhuys T, Staelens S, Van Nieuwenhuyse B, Deleye S, Hallez H, Vonck K, Raedt R, Wadman W, Boon P (2010) Hippocampal deep brain stimulation induces decreased rCBF in the hippocampal formation of the rat. Neuroimage 52:55–61

    Article  PubMed  Google Scholar 

  • Xiong Y, Mahmood A, Chopp M (2013) Animal models of traumatic brain injury. Nat Rev Neurosci 14:128–142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang L, Afroz S, Michelson HB, Goodman JH, Valsamis HA, Ling DSF (2010) Spontaneous epileptiform activity in rat neocortex after controlled cortical impact injury. J Neurotrauma 27:1541–1548

    Article  PubMed  Google Scholar 

  • Yu S, Kaneko Y, Bae E, Stahl CE, Wang Y, van Loveren H, Sanberg PR, Borlongan CV (2009) Severity of controlled cortical impact traumatic brain injury in rats and mice dictates degree of behavioral deficits. Brain Res 1:157–163

    Article  Google Scholar 

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Acknowledgements

We gratefully acknowledge the technical assistance of Tobias Hirnet, Dana Pieter and Wiesia Bobkiewicz (all UMC Mainz, Germany).

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429_2017_1452_MOESM1_ESM.tif

Fig S1 Study design and time lines. (a-c) Time lines for experimental groups (CCI and sham mice, 57 and 225 days survival after CCI) showing sequence and time points of behavioral tasks (a, b) and time points of SPECT and MRI (c). (d) Overview of sample sizes of behavioral tasks, brain histopathology using cresyl violet staining and immunohistochemistry, mRNA expression analysis by qPCR and SPECT and MRI (TIFF 7577 kb)

429_2017_1452_MOESM2_ESM.tif

Fig S2 TBI induces long-lasting changes in gait patterns. (a-g) Gait pattern analysis (Catwalk) revealed differences between CCI mice and sham mice at 40–42 dal in print position (a), cadence (b), stride length (c) and swing speed (d). At 209–211 dal, CCI mice differed compared to sham mice in swing (e), stance (f), step pattern (g) and cadence (h). Values represent mean ± SEM (early post-traumatic time point; sham: n = 15, CCI: n = 15; late post-traumatic time point; sham: n = 16, CCI: n = 18). *p < 0.05, **p < 0.01, ***p < 0,001, ****p < 0.0001. P values were calculated by Mann–Whitney U test (TIFF 14568 kb)

429_2017_1452_MOESM3_ESM.tif

Fig S3 TBI induces mild effects on fear conditioning and does not affect swimming speed in the MWM. (a, b) CCI mice exhibited enhanced context-dependent fear conditioning at 42 dal (p = 0.03) but no alterations in cued fear conditioning on 42 days and 212 days after TBI. (c, d) The swimming speed did not differ in CCI mice compared to sham mice. Values from fear-conditioning experiments and swimming speed are expressed as mean ± SEM (42 dal; sham: n = 15, CCI: n = 15; 212 dal; sham: n = 16, CCI: n = 18). *p < 0.05, calculated by Mann–Whitney U test (TIFF 20150 kb)

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Pöttker, B., Stöber, F., Hummel, R. et al. Traumatic brain injury causes long-term behavioral changes related to region-specific increases of cerebral blood flow. Brain Struct Funct 222, 4005–4021 (2017). https://doi.org/10.1007/s00429-017-1452-9

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