ABSTRACT Background: Previous results showed that quantitative changes in behavioural accuracies by rats that sustained a “mild” closed head injury were moderately correlated with the total areas (numbers) of anomalous neuronal soma within regions below the impact. Method: Water maze behavioural measures within one day or two months after a single impact of mechanical force over the right dorsal skull, with or without stunning and with or without subsequent pregnancy, were measured and compared to proportions of anomalous neurons under the impact site. Results: The consequences of the impact accommodated about 20% of the variance in the rats’ scores for less proficient spatial learning and memory. There were significantly more anomalous cells within right hemisphere below the impact site that were correlated with poorer initial maze learning. Maternal experience reduced the numbers of anomalous cells in the right limbic area only. Conclusion: These results suggest weak mechanical impacts produce changes in histomorphology within some neurons that are still evident two months later and that the presence of these anomalous clusters, corresponding to less than 1% of the cross-sectional area and below the resolution of contemporary MRI in human cases, are strongly correlated with specific behavioural impairments.
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W. Lado and M. Persinger, "Spatial Memory Deficits and Their Correlations with Clusters of Shrunken Neuronal Soma in the Cortices and Limbic System Following a “Mild’’ Mechanical Impact to the Dorsal Skull in Female Rats," Journal of Behavioral and Brain Science, Vol. 2 No. 3, 2012, pp. 333-342. doi: 10.4236/jbbs.2012.23038.
 D. R. Oppenheimer, “Microscopic Lesions in the Brain Following Head Injury,” Journal of Neurology and Neurosurgical Psychiatry, Vol. 31, No. 4, 1968, pp. 299-306.
 A. Peru, A. Beltramellow, V. Moro, L. Sattibaldi and G. Berlcchi, “Temporal and Permanent Signs of Interhemispheric Disconnection after Traumatic Brain Injury,” Neuropsychologica, Vol. 41, No. 5, 2003, pp. 634-643.
 B. C. Albensi, “Models of Brain Injury and Alterations in Synaptic Plasticity,” Journal of Neuroscience Research, Vol. 65, No. 4, 2001, pp. 279-283. doi:10.1002/jnr.1151
 A. Finset, A. W. Anke, E. Hofft, K. D. Roaldson, J. Pillgram-Larson and J. K. Stranghelle, “Cognitive Performance in Multiple Trauma Patients 3 Years after Injury,” Psychosomatic Medicine, Vol. 61, No. 4, 1999, pp. 576-583.
 R. J. Hamm, B. G. Lyeth, W. M. Jenkins, M. J. O’Donovan and B. R. Pike, “Selective Cognitive Impairment Following Traumatic Brain Injury in Rats,” Behavioural Brain Research, Vol. 59, No. 1-2, 1993, pp. 169-173.
 S. Marguilies, “The Postconcussion Syndrome after Mild Head Injury: Is Brain Damage Over Diagnosed?” Journal of Clinical Neuroscience, Vol. 7, No. 5, 2002, pp. 400-408. doi:10.1054/jocn.1999.0681
 T. W. McAlister, “Mild Traumatic Brain Injury and the Postconcussive Syndrome,” In: J. M. Silver, S. C. Yudofsky and S. C. Hales, Eds., Neuropsychiatry of Traumatic Brain Injury, American Psychiatric Press, New York, 1994, pp. 361-400.
 O. Zohar, G. V. Schreiber, J. P. Schwartz, P. G. Mullins and C. G. Pick, “Closed-Head Minimal Traumatic Brain Injury Produces Long-Term Cognitive Deficits in Mice,” Journal of Neuroscience, Vol. 118, No. 4, 2003, pp. 949-955. doi:10.1016/S0306-4522(03)00048-4
 H. Miller, “Accident Neurosis,” British Medical Journal, Vol. 1, 1961, pp. 992-998. doi:10.1136/bmj.1.5231.992
 J. T. Povlishock and T. H. Colburn, “Morphopathological Change Associated with Mild Head Injury,” In: H. S. Levin, M. D. Eisenberg and A. L. Benton, Eds., Mild Head Injury, Oxford University Press, New York, 1989, pp. 37-53.
 G. Lynch and M. Baudry, “The Biochemistry of Memory: a New and Specific Hypothesis,” Science, Vol. 224, No. 4, 1984, pp. 1057-1063. doi:10.1126/science.6144182
 A. C. Conti, R. Raghupathi, J. Q. Trojanowski and T. K. McIntosh, “Experimental Brain Injury Induces Regionally Distinct Apoptosis during the Acute and Delayed Post-Traumatic Period,” Journal of Neuroscience, Vol. 18, No. 4, 1998, pp. 5663-5672.
 A. A. Farooqui, S. E. Haunand and L. A. Horrocks, “Ischemia and Hypoxia: Basic Neurochemistry,” Raven Press, New York, 1993, pp. 867-883.
 C. Iadecola, “Bright and Dark Sides of Nitric Oxide in Ischemic Brain Injury,” Trends in the Neurosciences, Vol. 20, No. 3, 1997, pp. 132-139.
 S. M. Rothman and J. W. Olney, “Excitotoxicity and the NMDA Receptor,” Trends in the Neurosciences, Vol. 10, No. 7, 1987, pp. 299-302.
 Y. Shapira, A. M. Lam, A. A. Artu, C. Eng and L. Sotow, “Ketamine Alters Calcium and Magnesium in Brain Tissue Following Experimental Head Trauma in Rats,” Journal of Cerebral Blood Flow and Metabolism, Vol. 13, 1993, pp. 962-968. doi:10.1038/jcbfm.1993.120
 A. H. Dickenson, “Plasticity: Implications for Opioid and Other Pharmacological Interventions in Specific Pain States,” Behavioral and Brain Sciences, Vol. 20, No. 3, 2000, pp. 392-403.
 A. Dray, L. Urban and A. Dickenson, “Pharmacology of Chronic Pain,” Trends in Pharmaceutical Sciences, Vol. 15, No. 6, 1994, pp. 190-197.
 M. A. Persinger, “Neuropsychologica Principia Brevita: An Application to Traumatic (Acquired) Brain Injury,” Psychological Reports, Vol. 77, No. 3, 1995, pp. 707-724.
 C. J. Woolf and T. P. Doubell, “The Pathophysiology of Chronic Pain-Increased Sensitivity to Low Threshold A Beta-Fibre Inputs,” Current Opinions in Neurobiology, Vol. 4, No. 4, 1994, pp. 525-534.
 B. E. McKay, W. E. Lado, L. J. Martin and N. M. Fournier, “Learning and Memory in Agmatine-Treated Rats,” Pharmacology, Biochemistry and Behavior, Vol. 72, No. 3, 2002, pp. 551-557.
 K. R. Magnusson, B. Scruggs, J. Aniya, K. C. Wright, T. Ontl, Y. Xing and L. Bai, “Age-Related Deficits in Mice Performing Tasks in a Water Maze,” Behavioral Neuroscience, Vol. 117, No. 3, 2003, pp. 485-495.
 W. E. Lado and M. A. Persinger, “Mechanical Impacts to the Skulls of Rats Produce Specific Deficits in Maze Performance and Weight Loss: Evidence for Apoptosis of Cortical Neurons and Implications for Clinical Neuropsychology,” Perceptual and Motor Skills, Vol. 97, No. 3, 2003, pp. 1115-1127.
 D. M. Geddes, M. C. LaPlaca and R. S. Cargill, “Susceptibility of Hippocampal Neurons to Mechanically Induced Injury,” Experimental Neurology, Vol. 184, 2003, pp. 420-427. doi:10.1016/S0014-4886(03)00254-1
 Z. Cai, F. Xiao, B. Lee, I. A. Paul and P. G. Rhodes, “Prenatal Hypoxia-Ischemia Alters Expression and Activity of Nitric Oxide Synthase in the Young Brain and Causes Learning Deficits,” Brain Research Bulletin, Vol. 49, No. 5, 2000, pp. 359-365.
 W. Fu, J. Lee, Z. Guo and M. P. Mattson, “Seizures and Tissue Injury Induce Teleomerase in Hippocampal Microglial Cells,” Experimental Neurology, Vol. 178, No. 2, 2002, pp. 294-300. doi:10.1006/exnr.2002.8030
 W. P. Gray, K. May and L E. Sundstrom, “Seizure-Induced Dentate Neurogenesis Does Not Diminish with Age in Rats,” Neuroscience Letters, Vol. 330, 2002, pp. 235-238. doi:10.1016/S0304-3940(02)00810-8
 T. J. Shors, G. Meisegaes, A. Beylin, M. Zhao, T. Rydel and E. Gould, “Neurogenesis in the Adult Is Involved in the Formation of Trace Memories,” Nature, Vol. 410, 2001, pp. 372-376. doi:10.1038/35066584
 T. Shingo, C. Gregg, E. Enwere, H. Fujikawa, R. Hassam, C. Geary, J. C. Cross and S. Weiss, “Pregnancy-Stimulated Neurogenesis in the Adult Female Forebrain Mediated by Prolactin,” Science, Vol. 299, No. 5603, 2003, pp. 117-200. doi:10.1126/science.1076647
 H. Jeltsch, F. Betrand, C. Lazarus and J. C. Cassell, “Cognitive Performances and Locomotor Activity Following Dentate Granule Cell Damage in Rats: Role of Lesion Extent and Type of Memory Tests,” Neurobiology of Learning and Memory, Vol. 76, 2001, pp. 81-105.
 G. F. Lafreniere, O. Peredery and M. A. Persinger, “Progressive Accumulation of Large Aggregates of Calcium Containing Polysaccharides and Basophilic Debris within Specific Thalamic Nuclei after Lithium/Pilocarpine Induced Seizures,” Brain Research Bulletin, Vol. 28, No. 5, 1992, pp. 825-830. doi:10.1016/0361-9230(92)90268-3
 F. R. Ferraro, “Cognitive Slowing after Closed Head Injury,” Brain and Cognition, Vol. 32, No. 3, 1996, pp. 429-440. doi:10.1006/brcg.1996.0075
 D. H. Lowenstein, M. J. Thomas, S. H. Smith and T. K. McIntosh, “Selective Vulnerability of Dentate Hilar Neurons Following Traumatic Brain Injury: A Potential Mechanistic Link between Head Injuries and Disorders of the Hippocampus,” Journal of Neuroscience, Vol. 12, No. 12, 1992, pp. 4846-4853.
 D. M. Barros, T. Mello Souza, T. De David, H. Choi, A. Aguzzoli, C. Madche, P. Ardenghi, J. H. Medina and I. Izquierdo, “Simultaneous Modulation of Retrieval by Dopaminergic D(1), Beta-Noradrenergic, Serotonergic 1-A and Cholinergic Muscarinic Receptors in Cortical Structures of the Rat,” Behavioral Brain Research, Vol. 124, 2001, pp. 1-7. doi:10.1016/S0166-4328(01)00208-X
 O. Piot-Grosjean, F. Wahl, O. Gobbo and M. Stutzmann, “Assessment of Sensorimotor and Cognitive Deficits Induced by Moderate Traumatic Brain Injury in the Right Parietal Cortex of the Rat,” Neurobiological Disorders, Vol. 8, No. 6, 2001, pp. 1082-1093.
 S. Hogg, D. J. Sanger and P. C. Moser, “Mild Traumatic Lesions of the Right Parietal Cortex in the Rat: Characterization of a Conditioning Freezing Deficit and its reversal b Y Dizoilpine,” Behavioral Brain Research, Vol. 93, 1998, pp. 157-165.
 M. R. Foy, M. E. Stanton, S. Levin and R. F. Thompson, “Behavioural Stress Impairs Long-Term Potentiation in Rodent Hippocampus,” Behavioral Neural Biology, Vol. 48, No. 1, 1987, pp. 138-149.
 M. Maroun and G. Richter-Levin, “Exposure to Acute Stress Blocks the Induction of Long Term Potentiation of the Amygdala-Prefrontal Cortex Pathway in Vivo,” Journal of Neuroscience, Vol. 23, No. 11, 2003, pp. 4406-4409.
 J. Wang, I. Akirav and G. Richter-Levin, “Short-Term Behavioural and Electrophysiological Consequences of Underwater Trauma,” Physiology and Behavior, Vol. 70, 2000, pp. 327-332. doi:10.1016/S0031-9384(00)00274-2
 L. Xu, R. Anwyl and M. J. Rowan, “Behavioural Stress Facilitates the Induction of Long-Term Depression in the Hippocampus,” Nature, Vol. 387, 1997, pp. 497-500.
 E. Moor, R. Kohen, R. J. Reiter and E. Shohami, “Closed Head Injury Increases Extracellular Levels of Antioxidants in Rat Hippocampus in Vivo: An Adaptive Mechanism,” Neuroscience Letters, Vol. 316, 2001, pp. 169-172. doi:10.1016/S0304-3940(01)02394-1
 A. D. Bershadsky, N. Q. Balaban and B. Geiger, “Adhesion-Dependent Cell Mechanosensitivity,” Annual Review of Cell and Developmental Biology, Vol. 19, 2003, pp. 677-695. doi:10.1146/annurev.cellbio.19.111301.153011
 C. J. P. Oswald, D. M. Bannerman, B. K. Yee, J. N. P. Rawlins, R. C. Honey and M. Good, “Entorhinal Cortex Lesions Disrupt Transition between the Use of Intra and Extra-Maze Cues for Navigation of the Water Maze,” Behavioral Neuroscience, Vol. 117, No. 3, 2003, pp. 588-595. doi:10.1037/0735-7044.117.3.588
 R. D. Burwell, “The Parahippocampal Regions: Corticocortical Connectivity,” In: M. Witter, Ed., Annals of the New York Academy of Sciences, Vol. 911, 2000, pp. 25-42.
 T. M. McMillan and E. E. Glucksman, “Neuropsychology of Moderate Head Injury,” Journal of Neurology and Neurosurgical Psychiatry, Vol. 50, 1987, pp. 393-397.
 N. A. Shaw, “The neurophysiology of concussion,” Progress in Neurobiology, Vol. 67, 2002, pp. 281-344.
 R. Melzack, “From Gate to the Neuromatrix,” Pain (suppl) Vol. 6, 1999, pp. S121-S126.
 D. M. Bear, “Temporal Lobe Epilepsy—A Syndrome of Sensory-Limbic Hyperconnection,” Cortex, Vol. 15, 1979, pp. 357-384.
 D. M. Bear and P. Fedio, “Quantitative Analysis of Interictal Behavior in Temporal Lobe Epilepsy,” Archives of Neurology, Vol. 34, No. 8, 1977, pp. 454-467.
 R. J. Sbordone and J. H. Jennison, “A Comparison of OBD-168 and MMPI to Assess the Emotional Adjustment of Traumatic Brain Injured Patients to Their Cognitive Deficits,” Clinical Neuropsychology, Vol. 5, 1983, pp. 87-88.
 W. E. Lado and M. A. Persinger, “Increased Conditioned Immobility and Weight Loss in Rats Following Mechanical Impacts to the Skull That Do Not Produce Loss of Consciousness,” Central European Journal of Biology Vol. 3, No. 4, 2008, pp. 422-430.