MRI  Vol.4 No.2 , August 2015
Temporal and Spatial Changes in the Pattern of Iba1 and CD68 Staining in the Rat Brain Following Severe Traumatic Brain Injury
ABSTRACT
We have previously demonstrated that acute treatment with low dose methamphetamine is neuroprotectivein a rat model of severe traumatic brain injury (TBI). Using gene expression analysis, we further showed that methamphetamine treatment significantly reduced the expression of pro-inflammatory genes after severe TBI. Therefore, to further investigate the potential effects of methamphetamine treatment on the neuroinflammatory response, we examined immunofluorescent staining of Iba1 and CD68, two marker of neuroinflammation, in the rat lateral fluid percussion injury model of severe TBI. In this study, we observed temporal and spatial alterations in the pattern of Iba1 and CD68 labeling within two weeks after severe TBI. In general, methamphetamine treatment did not dramatically alter the pattern of Iba1 and CD68 staining. However, we did observe a unique and significant drug-induced increase of Iba1 labeling within the granule cell layer of the dentate gyrusat 48 hours post injury. We also observed rod-shaped Iba1+ cells within the core lesion in the cortex. These cells showed variable staining with CD68 and aligned most closely with MAP2+ neuronal processes. Thus, acute treatment with low-dose methamphetamine after severe TBI caused a transient bilateral increase of Iba1+ cells within the granule layer of the dentate gyrus but did not alter the overall temporal and regional pattern of Iba1 and CD68 staining within the cortex, periventricular white matter, fimbria, or thalamus.

Cite this paper
Smith, D. , Brooks, D. , Wohlgehagen, E. , Rau, T. and Poulsen, D. (2015) Temporal and Spatial Changes in the Pattern of Iba1 and CD68 Staining in the Rat Brain Following Severe Traumatic Brain Injury. Modern Research in Inflammation, 4, 9-23. doi: 10.4236/mri.2015.42002.
References
[1]   Hung, C. and Chen, J.W. (2012) Treatment of Post-Traumatic Epilepsy. Current Treatment Options in Neurology, 14, 293-306. http://dx.doi.org/10.1007/s11940-012-0178-5

[2]   Tiesman, H.M., Konda, S. and Bell, J.L. (2011) The Epidemiology of Fatal Occupational Traumatic Brain Injury in the U.S. American Journal of Preventive Medicine, 41, 61-67.
http://dx.doi.org/10.1016/j.amepre.2011.03.007

[3]   Hernandez-Ontiveros, D.G., Tajiri, N., Acosta, S., et al. (2013) Microglia Activation as a Biomarker for Traumatic Brain Injury. Frontiers in Neurology, 4, 30. http://dx.doi.org/10.3389/fneur.2013.00030

[4]   Mehndiratta, P. and Sajatovic, M. (2013) Treatments for Patients with Comorbid Epilepsy and Depression: A Systematic Literature Review. Epilepsy & Behavior, 28, 36-40.
http://dx.doi.org/10.1016/j.yebeh.2013.03.029

[5]   Xiong, Y., Mahmood, A. and Chopp, M. (2013) Animal Models of Traumatic Brain Injury. Nature Reviews Neuroscience, 14, 128-142. http://dx.doi.org/10.1038/nrn3407

[6]   Loane, D.J. and Byrnes, K.R. (2010) Role of Microglia in Neurotrauma. Neurotherapeutics, 7, 366-377. http://dx.doi.org/10.1016/j.nurt.2010.07.002

[7]   Kumar, A. and Loane, D.J. (2012) Neuroinflammation after Traumatic Brain Injury: Opportunities for Therapeutic Intervention. Brain, Behavior, and Immunity, 26, 1191-1201.
http://dx.doi.org/10.1016/j.bbi.2012.06.008

[8]   Carson, M.J., Doose, J.M., Melchior, B., et al. (2006) CNS Immune Privilege: Hiding in Plain Sight. Immunological Reviews, 213, 48-65. http://dx.doi.org/10.1111/j.1600-065X.2006.00441.x

[9]   Su, P., Zhang, J., Zhao, F., et al. (2014) The Interaction between Microglia and Neural Stem/Precursor Cells. Brain Research Bulletin, 109, 32-38. http://dx.doi.org/10.1016/j.brainresbull.2014.09.005

[10]   Hanisch, U.K. (2013) Functional Diversity of Microglia—How Heterogeneous Are They to Begin with? Frontiers in Cellular Neuroscience, 7, 65. http://dx.doi.org/10.3389/fncel.2013.00065

[11]   Perry, V.H., Nicoll, J.A. and Holmes, C. (2010) Microglia in Neurodegenerative Disease. Nature Reviews Neurology, 6, 193-201. http://dx.doi.org/10.1038/nrneurol.2010.17

[12]   Rizzo, F., Riboldi, G., Salani, S., Nizzardo, M., Simone, C., Corti, S., et al. (2014) Cellular Therapy to Target Neuroinflammation in Amyotrophic Lateral Sclerosis. Cellular and Molecular Life Sciences, 71, 999-1015. http://dx.doi.org/10.1007/s00018-013-1480-4

[13]   Chen, Z., Jalabi, W., Hu, W., Park, H.-J., Gale, J.T., Kidd, G.J., et al. (2014) Microglial Displacement of Inhibitory Synapses Provides Neuroprotection in the Adult Brain. Nature Communications, 5, Article No. 4486. http://dx.doi.org/10.1038/ncomms5486

[14]   Acosta, S.A., Tajiri, N., Shinozuka, K., Ishikawa, H., Sanberg, P.R., Sanchez-Ramos, J., et al. (2014) Combination Therapy of Human Umbilical Cord Blood Cells and Granulocyte Colony Stimulating Factor Reduces Histopathological and Motor Impairments in an Experimental Model of Chronic Traumatic Brain Injury. PLoS ONE, 9, e90953. http://dx.doi.org/10.1371/journal.pone.0090953

[15]   Perez-Polo, J.R., Rea, H.C., Johnson, K.M., Parsley, M.A., Unabia, G.C., Xu, G.J., et al. (2013) Inflammatory Consequences in a Rodent Model of Mild Traumatic Brain Injury. Journal of Neurotrauma, 30, 727-740. http://dx.doi.org/10.1089/neu.2012.2650

[16]   Graeber, M.B. and Mehraein, P. (1994) Microglial Rod Cells. Neuropathology and Applied Neurobiology, 20, 178-180.

[17]   Ziebell, J.M., Taylor, S.E., Cao, T., Harrison, J.L. and Lifshitz, J. (2012) Rod Microglia: Elongation, Alignment, and Coupling to Form Trains across the Somatosensory Cortex after Experimental Diffuse Brain Injury. Journal of Neuroinflammation, 9, 247. http://dx.doi.org/10.1186/1742-2094-9-247

[18]   Ding, G.L., Chopp, M., Poulsen, D.J., Li, L., Qu, C., Li, Q., et al. (2013) MRI of Neuronal Recovery after Low-Dose Methamphetamine Treatment of Traumatic Brain Injury in Rats. PLoS ONE, 8, e61241. http://dx.doi.org/10.1371/journal.pone.0061241

[19]   Rau, T.F., Kothiwal, A.S., Rova, A.R., Brooks, D.M. and Poulsen, D.J. (2012) Treatment with Low-Dose Methamphetamine Improves Behavioral and Cognitive Function after Severe Traumatic Brain Injury. Journal of Trauma and Acute Care Surgery, 73, S165-S172.
http://dx.doi.org/10.1097/ta.0b013e318260896a

[20]   Rau, T.F., Kothiwal, A.S., Rova, A.R., Brooks, D.M., Rhoderick, J.F., Poulsen, A.J., et al. (2014) Administration of Low Dose Methamphetamine 12 h after a Severe Traumatic Brain Injury Prevents Neurological Dysfunction and Cognitive Impairment in Rats. Experimental Neurology, 253, 31-40. http://dx.doi.org/10.1016/j.expneurol.2013.12.001

[21]   Rau, T.F., Kothiwal, A., Zhang, L., Ulatowski, S., Jacobson, S., Brooks, D.M., et al. (2011) Low Dose Methamphetamine Mediates Neuroprotection through a PI3K-AKT Pathway. Neuropharmacology, 61, 677-686. http://dx.doi.org/10.1016/j.neuropharm.2011.05.010

[22]   Bauer, J., Sminia, T., Wouterlood, F.G. and Dijkstra, C.D. (1994) Phagocytic Activity of Macrophages and Microglial Cells during the Course of Acute and Chronic Relapsing Experimental Autoimmune Encephalomyelitis. Journal of Neuroscience Research, 38, 365-375.
http://dx.doi.org/10.1002/jnr.490380402

[23]   Chung, R.S., Vickers, J.C., Chuah, M.I. and West, A.K. (2003) Metallothionein-IIA Promotes Initial Neurite Elongation and Postinjury Reactive Neurite Growth and Facilitates Healing after Focal Cortical Brain Injury. Journal of Neuroscience, 23, 3336-3342.

[24]   Hirko, A.C., Dallasen, R., Jomura, S. and Xu, Y. (2008) Modulation of Inflammatory Responses after Global Ischemia by Transplanted Umbilical Cord Matrix Stem Cells. Stem Cells, 26, 2893-2901.
http://dx.doi.org/10.1634/stemcells.2008-0075

[25]   Sternberger, N.H. and Sternberger, L.A. (1987) Blood-Brain Barrier Protein Recognized by Monoclonal Antibody. Proceedings of the National Academy of Sciences of the United States of America, 84, 8169-8173. http://dx.doi.org/10.1073/pnas.84.22.8169

[26]   Trifilieff, P., Feng, B., Urizar, E., Winiger, V., Ward, R.D., Taylor, K.M., et al. (2013) Increasing Dopamine D2 Receptor Expression in the Adult Nucleus Accumbens Enhances Motivation. Molecular Psychiatry, 18, 1025-1033. http://dx.doi.org/10.1038/mp.2013.57

[27]   Donnelly, D.J., Gensel, J.C., Ankeny, D.P., van Rooijen, N. and Popovich, P.G. (2009) An Efficient and Reproducible Method for Quantifying Macrophages in Different Experimental Models of Central Nervous System Pathology. Journal of Neuroscience Methods, 181, 36-44.
http://dx.doi.org/10.1016/j.jneumeth.2009.04.010

[28]   Taylor, S.E., Morganti-Kossmann, C., Lifshitz, J. and Ziebell, J.M. (2014) Rod Microglia: A Morphological Definition. PLoS ONE, 9, e97096. http://dx.doi.org/10.1371/journal.pone.0097096

[29]   Walker, K.R. and Tesco, G. (2013) Molecular Mechanisms of Cognitive Dysfunction Following Traumatic Brain Injury. Frontiers in Aging Neuroscience, 5, 29. http://dx.doi.org/10.3389/fnagi.2013.00029

[30]   Thomas, D.M., Walker, P.D., Benjamins, J.A., Geddes, T.J. and Kuhn, D.M. (2004) Methamphetamine Neurotoxicity in Dopamine Nerve Endings of the Striatum Is Associated with Microglial Activation. Journal of Pharmacology and Experimental Therapeutics, 311, 1-7. http://dx.doi.org/10.1124/jpet.104.070961

[31]   Adnan, A., Crawley, A., Mikulis, D., Moscovitch, M., Colella, B. and Green, R. (2013) Moderate-Severe Traumatic Brain Injury Causes Delayed Loss of White Matter Integrity: Evidence of Fornix Deterioration in the Chronic Stage of Injury. Brain Injury, 27, 1415-1422.
http://dx.doi.org/10.3109/02699052.2013.823659

[32]   Kou, Z. and VandeVord, P.J. (2014) Traumatic White Matter Injury and Glial Activation: From Basic Science to Clinics. Glia, 62, 1831-1855. http://dx.doi.org/10.1002/glia.22690

[33]   Wang, G., Zhang, J., Hu, X., Zhang, L., Mao, L., Jiang, X., et al. (2013) Microglia/Macrophage Polarization Dynamics in White Matter after Traumatic Brain Injury. Journal of Cerebral Blood Flow & Metabolism, 33, 1864-1874. http://dx.doi.org/10.1038/jcbfm.2013.146

[34]   Wang, T., Huang, X.J., Van, K.C., Went, G.T., Nguyen, J.T. and Lyeth, B.G. (2014) Amantadine Improves Cognitive Outcome and Increases Neuronal Survival after Fluid Percussion Traumatic Brain Injury in Rats. Journal of Neurotrauma, 31, 370-377. http://dx.doi.org/10.1089/neu.2013.2917

[35]   Hazra, A., Macolino, C., Elliott, M.B. and Chin, J. (2014) Delayed Thalamic Astrocytosis and Disrupted Sleep-Wake Patterns in a Preclinical Model of Traumatic Brain Injury. Journal of Neuroscience Research, 92, 1434-1445. http://dx.doi.org/10.1002/jnr.23430

[36]   Gemma, C. and Bachstetter, A.D. (2013) The Role of Microglia in Adult Hippocampal Neurogenesis. Frontiers in Cellular Neuroscience, 7, 229. http://dx.doi.org/10.3389/fncel.2013.00229

[37]   Kettenmann, H., Kirchhoff, F. and Verkhratsky, A. (2013) Microglia: New Roles for the Synaptic Stripper. Neuron, 77, 10-18. http://dx.doi.org/10.1016/j.neuron.2012.12.023

[38]   Glushakova, O.Y., Johnson, D. and Hayes, R.L. (2014) Delayed Increases in Microvascular Pathology after Experimental Traumatic Brain Injury Are Associated with Prolonged Inflammation, Blood-Brain Barrier Disruption, and Progressive White Matter Damage. Journal of Neurotrauma, 31, 1180-1193.
http://dx.doi.org/10.1089/neu.2013.3080

 
 
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