Possible Coexistence of Traumatic Cerebral Microbleeds and Axonal Injury? Postmortem Immunohistochemical Analysis
Article content
Abstract
Diffuse axonal injury (DAI) is a common type of traumatic brain injury, whose detection remains a significant clinical challenge. Recent studies suggest that traumatic cerebral microbleeds (TCMs) may serve as indirect indicators of axonal injury. Given the similar mechanisms underlying the formation of axonal injury and cerebral microbleeds, the aim of this study is to investigate the potential association between these two types of cerebral trauma.
In the total sample of 36 brains, axonal injury was detected in 32 cases (88.9%), identical to the incidence of traumatic cerebral microbleeds. βAPP immunopositivity was relatively evenly distributed across the examined brain regions, with slightly stronger expression in the posterior brain regions and the highest frequency of intense immunopositivity in the pons, albeit without statistical significance. The χ2 test, along with the Spearman correlation test, indicates an association between traumatic microbleeds in the genu of the corpus callosum and βAPP immunopositivity in all four observed brain regions, with the strongest correlation observed in the genu of the corpus callosum (p=0.011).
βAPP immunohistochemical staining revealed a relatively uniform distribution of axonal injury and microhemorrhages throughout the examined mid-sagittal brain structures. A slightly stronger βAPP expression was detected in the pons, though without statistical significance. The observed positive correlation between traumatic cerebral microbleeds and axonal injury in the anterior aspects of the corpus callosum aligns with current assumptions that the mid-sagittal brain regions are critical for the relationship between these two types of cerebral lesions
Keywords
Forensic sciences, Craniocerebral trauma, Diffuse axonal injury, Traumatic cerebral microbleeds, Amyloid beta-peptide
Downloads
References
Dewan MC, Rattani A, Gupta S, Baticulon RE, Hung YC, Punchak M et al. Estimating the global incidence of traumatic brain injury. J Neurosurg. 2019;130:1080–97.
Guan B, Anderson DB, Chen L, Feng S, Zhou H. Global, regional and national burden of traumatic brain injury and spinal cord injury, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. BMJ Open 2023;13:e075049. doi:10.1136/bmjopen-2023-075049
Humble SS, Wilson DL, Wang L, Long AD, Smith AM, Siktberg CJ et al. Prognosis of diffuse axonal injury with traumatic brain injury. J Trauma Acute Care Surg. 2018;85(1):155-9.
Figueira Rodrigues Vieira G, Guedes Correa JF. Early computed tomography for acute post-traumatic diffuse axonal injury: a systematic review. Neuroradiology. 2020;62(6):653-60.
Watanabe J, Maruya J, Kanemaru Y, Miyauchi T, Nishimaki K. Transient disappearance of microbleeds in the subacute period based on T2*-weighted gradient echo imaging in traumatic brain injury. Acta Neurochir (Wien). 2016;158(7):1247–50.
Davidsson J, Risling M. A new model to produce sagittal plane rotational induced diffuse axonal injuries. Front Neurol. 2011;2:41.
Haller S, Vernooij MW, Kuijer JPA, Larsson EM, Jäger HR, Barkhof F. Cerebral Microbleeds: Imaging and Clinical Significance. Radiology. 2018;287(1):11-28.
Andreasen SH, Andersen KW, Conde V, Dyrby TB, Puonti O, Kammersgaard LP et al. Limited co-localization of microbleeds and microstructural changes after severe traumatic brain injury. J Neurotrauma. 2020;37(4):581-92.
Chiara Ricciardi M, Bokkers RPH, Butman JA, Hammoud DA, Pham DL, Warach S et al. Trauma - specific brain abnormalities in suspected mild traumatic brain injury patients identified in the first 48 hours after injury: a blinded magnetic resonance imaging comparative study including suspected acute minor stroke patients. J Neurotrauma. 2017;34:23–30.
Viswanathan A, Chabriat H, Cerebral microhemorrhage, Stroke. 2006;37:550-5.
Mori Y, Murakami M, Arima Y, Zhu D, Terayama Y, Komai Y et al. Early pathological alterations of lower lumbar cords detected by ultrahigh-field MRI in a mouse multiple sclerosis model. Int Immunol. 2014;26:93-101.
Gentleman SM, Roberts GW, Gennarelli TA, Maxwell WL, Adams JH, Kerr S et al. Axonal injury: a universal consequence of fatal closed head injury? Acta Neuropathol. 1995;89(6):537-43.
Bertozzi G, Maglietta F, Sessa F, Scoto E, Cipolloni L, Di Mizio G, Salerno M, Pomara C. Traumatic Brain Injury: A Forensic Approach: A Literature Review. Curr Neuropharmacol. 2020;18(6):538-50.
James SL, Theadom A, Ellenbogen R, Bannick M, Mountjoy-Venning WC, Lucchesi L et al. Global, regional, and national burden of traumatic brain injury and spinal cord injury. Lancet Neurol. 2019;18:56–87.
Wilson BA, Winegardner J, van Heugten CM, Ownsworth T. Neuropsychological Rehabilitation: The International Handbook. London, Routledge. 2017;6:6.
Mollayeva T, Mollayeva S, Pacheco N, Colantonio A. Systematic Review of Sex and Gender Effects in Traumatic Brain Injury: Equity in Clinical and Functional Outcomes. Front Neurol. 2021;12:678971.
Jolly A, Bălăeţ M, Azor A, Friedland D, Sandrone S, Graham N et al. Detecting axonal injury in individual patients after traumatic brain injury, Brain, 2021;144(1):92–113.
Javeed F, Rehman L, Afzal A, Abbas A. Outcome of diffuse axonal injury in moderate and severe traumatic brain injury. Surg Neurol Int. 2021;12:384.
Lee HJ, Sun HW, Lee JS, Choi NJ, Jung Yj, Hong S. Clinical Outcomes of Diffuse Axonal Injury According to Radiological Grade. J Trauma Inj. 2018;31(2):51-57.
Skandsen T, Kvist KA, Solheim O, Strand IH, Folvik M, Vik A. Prevalence and impact of diffuse axonal injury in patients with moderate and severe head injury: a cohort study of early magnetic resonance imaging findings and 1-year outcome. J Neurosurg. 2010;113:556–63.
Moen KG, Brezova V, Skandsen T, Haberg AK, Folvik M, Vik A. Traumatic axonal injury: the prognostic value of lesion load in corpus callosum, brain stem, and thalamus in different magnetic resonance imaging sequences. J Neurotrauma. 2014;31(17):1486-96.
Moe HK, Myhr JL, Moen KG, Haberg AK; Skandsen T, Vik A. Association of cause of injury and traumatic axonal injury: a clinical MRI study of moderate and severe traumatic brain injury. J Neurosurg 2019;11(10):1-9.
Castaño-Leon MA, Cicuendez M, Navarro-Main B, Paredes I, Munarriz MP, Hilario A et al. Traumatic axonal injury: is the prognostic information produced by conventional MRI and DTI complementary or supplementary? J Neurosurg. 2022; 136:242-56.
Vieira RCA, Zumerkorn Pipek L, Vieira de Oliveira D, Paiva SW, Cardoso de Sousa MR. The relationship between injury characteristics and post-traumatic recovery after diffuse axonal injury. Biomedicines, 2024; 12:311.
Delteil C, Manlius T, Bailly N, Godio-Raboutet Y, Piercecchi-Marti MD, Tuchtan L et al. Traumatic axonal injury: Clinic, forensic and biomechanics perspectives. LegalMedicine, 2024; 70:102465.
Hütter BO, Altmeppen J, Kraff O, Maderwald S, Theysohn JM, Ringelstein A et al. Higher sensitivity for traumatic cerebral microbleeds at 7 T ultra-high field MRI: is it clinically significant for the acute state of the patients and later quality of life? Ther Adv Neurol Disord. 2020;13:1-12.
Toth A, Kornyei B, Kovacs N, Rostas T, Buki A, Doczi T et al. Both hemorrhagic and non-hemorrhagic traumatic MRI lesions are associated with the microstructural damage of the normal appearing white matter. Behav Brain Res. 2018;340:106–16.
Studerus-Germann AM, Gautschi OP, Bontempi P, Thiran JP, Daducci A, Romascano D et al. Central nervous system microbleeds in the acute phase are associated with structural integrity by DTI one year after mild traumatic brain injury: a longitudinal study. Neurol Neurochir Pol 2018 Nov-Dec;52(6):710-9.
Adams JH, Doyle D, Ford I, Gennarelli TA, Graham DI.. Diffuse axonal injury in head injury: definition, diagnosis and grading. Histopathology. 1989;15:49–59.
Irimia A, Van Horn JD, Vespa PM. Cerebral microhemorrhages due to traumatic brain injury and their effects on the aging human brain. Neurobiol Aging. 2018;66:158–64.
Glushakova OY, Johnson D, Hayes RL. Delayed increases in microvascular pathology after experimental traumatic brain injury are associated with prolonged inflammation, blood-brain barrier disruption, and progressive white matter damage. J Neurotrauma. 2014;31(13):1180-93.
de Haan S, de Groot JC, Jacobs B, van der Naalt J. The association between microhaemorrhages and post - traumatic functional outcome in the chronic phase after mild traumatic brain injury. Neuroradiology. 2017;59(10):963–9.
Griffin AD, Turtzo LC, Parikh GY, Tolpygo A, Lodato Z, Moses AD et al. Traumatic microbleeds suggest vascular injury and predict disability in traumatic brain injury. Brain. 2019;142(11):3550–64.
Ubukata S, Ueda K, Sugihara G, Yassin W, Aso T, Fukuyama H et al. Corpus callosum pathology as a potential surrogate marker of cognitive impairment in diffuse axonal injury. J Neuropsychiatry Clin Neurosci. 2016;28(2):97–103.
Rutgers DR, Fillard P, Paradot G, Tadie M, Lasjaunias P, Ducreux D. Diffusion tensor imaging characteristics of the corpus callosum in mild, moderate, and severe traumatic brain injury. Am J Neuroradiol. 2008;29(9):1730-5.
Hageman G, Hof J, Nihom J. Susceptibility-weighted MRI and microbleeds in mild traumatic brain injury: prediction of posttraumatic complaints? Eur Neurol 2022;85:177–85.
Dahl J, Tenovuo O, Posti JP, Hirvonen J, Katila AJ, Frantzén J, et al. Cerebral microbleeds and structural white matter integrity in patients with traumatic brain injury - a diffusion tensor imaging study. Front. Neurol. 2022; 13:888815
Article details
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
You must read and accept the copyright terms and conditions(click here for copyright terms).