TRAUMA CRANEOENCEFÁLICO: FISIOPATOLOGÍA Y MOLÉCULAS PROTECTORAS
DOI:
https://doi.org/10.51437/nj.v29i3.394Keywords:
trauma craneoencefálico, tce, Terbutilhidroquinona, fisiopatología, Proteína Precursora Amiloide, Factor Nuclear Eritroide Similar al Factor 2Abstract
El trauma craneoencefálico es una patología que se caracteriza por presentar alguna alteración neurológica secundaria a una lesión traumática producida por la liberación de una fuerza externa, bien sea, química, mecánica, térmica, eléctrica, radiante o una mezcla de ellas; ocasionando daño estructural en la bóveda craneana y su contenido. Presenta diversas clasificaciones: según el mecanismo del trauma, según la severidad del trauma, o conforme a la correlación anatomopatológica. El trauma afecta a más de 60 millones de personas cada año en todo el mundo, mayoritariamente en países con bajos y medianos ingresos en los que ocurre el 90% de los casos, siendo los accidentes de tránsito el principal causal de la morbimortalidad asociada. Fisiopatológicamente se identifican la injuria primaria y secundaria. Ante la gravedad del TCE este artículo plantea describir algunas investigaciones sobre posibles blancos terapéuticos que pudieran mejorar la sobrevida de los pacientes o aminorar las lesiones subsecuentes del trauma, entre ellas la Proteína Precursora Amiloide, el Factor Nuclear Eritroide Similar al Factor 2 y la Terbutilhidroquinona. En este documento se abordan estas moléculas en el contexto del trauma, según la literatura desde 1990 hasta la actualidad, y se excluyeron documentos relacionados con la población pediátrica y obstétrica. Las tres moléculas tienen evidencia preclínica que las propone como potenciales blancos para intervención en trauma craneoencefálico, actuando sobre puntos clave de la fisiopatología del trauma.
References
Ministerio de Salud y Protección Social, Rubiano Escobar AM et al. Guía
colombiana de práctica clínica para el diagnóstico y tratamiento de
pacientes adultos con trauma craneoencefálico severo [Internet].
Ministerio de Salud y Protección Social. 2016 [citado 2022Oct18].
Disponible en
https://www.minsalud.gov.co/sites/rid/Lists/BibliotecaDigital/RIDE/DE/C
A/gpc-profesionales-completa-adultos-trauma-craneoencefalicosevero.pdf
Centers for Disease Control and Prevention. . Report to Congress on
Traumatic Brain Injury in the United States: Epidemiology and
Rehabilitation. [Internet]. 2015 [citado 2022Oct26]. Disponible en:
https://www.cdc.gov/traumaticbraininjury/pdf/tbi_report_to_congress_e
pi_and_rehab-a.pdf?_hsenc=p2ANqtz-
ezXS6LlptZETVIRCTLawzpF2Zh_QbH8sKPHJXRI45yicklm4DOLaP_VlRazO
wEVBIIwQq94BCinpyTUB4EWNgAACHQ&_hsmi=67061850
Ng S and Lee A. Traumatic brain injuries: Pathophysiology and potential
therapeutic targets [Internet]. Frontiers. Frontiers; 2019 [citado
Oct16]. Disponible en:
https://www.frontiersin.org/articles/10.3389/fncel.2019.00528/full
Gabbe BJ, Cameron PA, Finch CF. The status of the Glasgow Coma Scale.
Emergency Medicine Australasia. 2003Jul25;15(4):353–60.
Patil A, Srinivasarangan M, Javali RH, LNU K, LNU S, LNU S. Comparison of
Injury Severity Score, new injury severity score, revised trauma score and
trauma and injury severity score for mortality prediction in elderly trauma
patients. Indian Journal of Critical Care Medicine. 2019Feb23;23(2):73–7.
Lesko MM, Woodford M, White L, O'Brien SJ, Childs C, Lecky FE. Using
abbreviated injury scale (AIS) codes to classify computed tomography (CT)
features in the marshall system. BMC Medical Research Methodology.
;10(1).
GEO-TBI. GEO-TBI [Internet]. Global Health Research Group on
Neurotrauma. 2023 [citado 2023Feb16]. Disponible en:
Dewan MC, Rattani A, Gupta S, Baticulon RE, Hung Y-C, Punchak M, et al.
Estimating the global incidence of traumatic brain injury. Journal of
Neurosurgery. 2018Apr27;130(4):1080–97.
Dunne J, Quiñones-Ossa GA, Still EG, Suarez MN, González-Soto JA, Vera
DS, et al. The epidemiology of traumatic brain injury due to traffic
accidents in Latin America: A narrative review. Journal of Neurosciences
in Rural Practice. 2020Apr2;11:287–90.
WHO. Global status report on road safety 2015 [Internet]. World Health
Organization. World Health Organization; 2015 [citado 2022Oct23].
Disponible en: https://www.afro.who.int/publications/global-statusreport-road-safety-2015
Skandsen T, Kvistad 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. Journal of Neurosurgery. 2010Sep;113(3):556–63.
Clifton GL, Coffey CS, Fourwinds S, Zygun D, Valadka A, Smith KR, et al.
Early induction of hypothermia for evacuated intracranial hematomas: A
post hoc analysis of two clinical trials. Journal of Neurosurgery.
;117(4):714–20.
Saatman, K. E., Duhaime, A. C., Bullock, R., Maas, A. I., Valadka, A., and
Manley, G. T. (2008). Classification of traumatic brain injury for targeted
therapies. J. Neurotrauma 25, 719–738. doi: 10.1089/neu.2008.0586
Chamoun, R., Suki, D., Gopinath, S. P., Goodman, J. C., and Robertson, C.
(2010). Role of extracellular glutamate measured by cerebral
microdialysis in severe traumatic brain injury. J. Neurosurg. 113, 564–570.
doi: 10.3171/2009.12.jns09689
Giménez Martín C, Zafra Gómez F, Aragón Rueda C. Fisiopatología de los
transportadores de glutamato y de glicina: Nuevas Dianas Terapéuticas.
Revista de Neurología. 2018Dicc16;67(12):491.
Luo, P., Fei, F., Zhang, L., Qu, Y., and Fei, Z. (2011). The role of glutamate
receptors in traumatic brain injury: implications for postsynaptic density
in pathophysiology. Brain Res. Bull. 85, 313–320. doi:
1016/j.brainresbull.2011.05.004
Niswender CM, Conn PJ. Metabotropic glutamate receptors: Physiology,
pharmacology, and disease. Annual Review of Pharmacology and
Toxicology. 2010;50(1):295–322.
Weber JT. Altered calcium signaling following traumatic brain injury.
Frontiers in Pharmacology. 2012Mar12;3.
Pérez-Burgos, Alamilla. El fosfatidilinositol-4,5-bifosfato y sus acciones
sobre los canales iónicos. Vol.21, No.2. 2010Ago25.
García N, García JJ, Correa F, Chávez E. The permeability transition pore as
a pathway for the release of mitochondrial DNA. Life Sciences.
Apr29;76(24):2873–80.
Hall, E. D., Detloff, M. R., Johnson, K., and Kupina, N. C. (2004).
Peroxynitrite-mediated protein nitration and lipid peroxidation in a
mouse model of traumatic brain injury. J. Neurotrauma 21, 9–20. doi:
1089/089771504772695904
Singh, I. N., Sullivan, P. G., Deng, Y., Mbye, L. H., and Hall, E. D. (2006). Time
course of post-traumatic mitochondrial oxidative damage and
dysfunction in a mouse model of focal traumatic brain injury: implications
for neuroprotective therapy. J. Cereb. Blood Flow Metab. 26, 1407–1418.
doi: 10.1038/sj.jcbfm.9600297
Ansari, M. A., Roberts, K. N., and Scheff, S. W. (2008a). Oxidative stress and
modification of synaptic proteins in hippocampus after traumatic brain
injury. Free Radic. Biol. Med. 45, 443–452. doi:
1016/j.freeradbiomed.2008.04.038
Lotocki, G., de Rivero Vaccari, J. P., Perez, E. R., Sanchez-Molano, J.,
Furones-Alonso, O., Bramlett, H. M., et al. (2009). Alterations in bloodbrain barrier permeability to large and small molecules and leukocyte
accumulation after traumatic brain injury: effects of post-traumatic
hypothermia. J. Neurotrauma 26, 1123–1134. doi: 10.1089/neu.2008.0802
Semple, B. D., Bye, N., Rancan, M., Ziebell, J. M., and Morganti-Kossmann,
M. C. (2010). Role of CCL2 (MCP-1) in traumatic brain injury (TBI): evidence
from severe TBI patients and CCL2−/− mice. J. Cereb. Blood Flow Metab. 30,
–782. doi: 10.1038/jcbfm.2009.262
Morganti-Kossmann, M. C., Rancan, M., Stahel, P. F., and Kossmann, T.
(2002). Inflammatory response in acute traumatic brain injury: a doubleedged sword. Cur. Opin. Crit. Care 8, 101–105. doi: 10.1097/00075198-
-00002
Mujica B M, González T G, Larraín G C, Miller T P, Castoldi L F. Resonancia
magnética cerebral en Daño axonal DIFUSO. Revista chilena de radiología.
;9(4).
Martínez J, Castro M. El Yin y el yang de la astrogliosis reactiva [Internet].
Ciencia UANL. 2021 [citado 2022Oct26]. Disponible en:
https://cienciauanl.uanl.mx/?p=10864
Perreau VM, Orchard S, Adlard PA, Bellingham SA, Cappai R, Ciccotosto
GD, et al. A domain level interaction network of amyloid precursor protein
and AΒ of alzheimer's disease. PROTEOMICS. 2010;10(12):2377–95.
Romero Tirado, M.A. et al. Proteína precursora del beta-amiloide (β-App)
y daño axonal difuso tras un traumatismo craneoencefálico: un punto de
vista forense. Med. leg. Costa Rica [online]. 2022, vol.39, n.2, pp.37-50. ISSN
-5287.
Plummer S, Van den Heuvel C, Thornton E, Corrigan F, Cappai R. The
neuroprotective properties of the amyloid precursor protein following
traumatic brain injury. Aging and disease. 2016Mar15;7(2):163.
Prox J, Rittger A, Saftig P. Physiological functions of the amyloid precursor
protein secretases ADAM10, BACE1, and Presenilin. Experimental Brain
Research. 2011Nov27;217(3-4):331–41.
Hiltunen M, van Groen T, Jolkkonen J. Functional roles of amyloid-β
protein precursor and amyloid-β peptides: Evidence from experimental
studies. Journal of Alzheimer's Disease. 2009May4;18(2):401–12.
Hornsten, A., Lieberthal, J., Fadia, S., Malins, R., Ha, L., Xu, X., et al. (2007).
APL-1, a Caenorhabditis elegans protein related to the human β-amyloid
precursor protein, is essential for viability. Proc. Natl. Acad. Sci. U S A 104,
–1976. doi: 10.1073/pnas.0603997104
Bourdet, I., Preat, T., and Goguel, V. (2015). The full-length form of the
Drosophila amyloid precursor protein is involved in memory formation. J.
Neurosci. 35, 1043–1051. doi: 10.1523/JNEUROSCI.2093-14.2015
Weyer, S. W., Klevanski, M., Delekate, A., Voikar, V., Aydin, D., Hick, M., et
al. (2011). APP and APLP2 are essential at PNS and CNS synapses for
transmission, spatial learning and LTP. EMBO J. 30, 2266–2280. doi:
1038/emboj.2011.119
Caldwell, J. H., Klevanski, M., Saar, M., and Müller, U. C. (2013). Roles of the
amyloid precursor protein family in the peripheral nervous system. Mech.
Dev. 130, 433–446. doi: 10.1016/j.mod.2012.11.001
Hefter D, Draguhn A. App as a protective factor in acute neuronal insults.
Frontiers in Molecular Neuroscience. 2017Feb2;10.
Otsuka, N., Tomonaga, M., and Ikeda, K. (1991). Rapid appearance of β-
amyloid precursor protein immunoreactivity in damaged axons and
reactive glial cells in rat brain following needle stab injury. Brain Res. 568,
–338. doi: 10.1016/0006-8993(91)91422-W
Lewén, A., Li, G. L., Nilsson, P., Olsson, Y., and Hillered, L. (1995). Traumatic
brain injury in rat produces changes of beta-amyloid precursor protein
immunoreactivity. Neuroreport. 6, 357–360. doi: 10.1097/00001756-
-00032
Lewén, A., Li, G. L., Olsson, Y., and Hillered, L. (1996). Changes in
microtubule-associated protein 2 and amyloid precursor protein
immunoreactivity following traumatic brain injury in rat: influence of MK-
treatment. Brain Res. 719, 161–171. doi: 10.1016/0006-
(96)00081-9
Thornton E, Vink R, Blumbergs PC, Van Den Heuvel C. Soluble amyloid
precursor protein α reduces neuronal injury and improves functional
outcome following diffuse traumatic brain injury in rats. Brain Research.
May15;1094(1):38–46.
Corrigan F, Vink R, Blumbergs PC, Masters CL, Cappai R, van den Heuvel
C. SAPPα rescues deficits in amyloid precursor protein knockout mice
following focal traumatic brain injury. Journal of Neurochemistry.
Apr20;122(1):208–20.
Ma T, Zhao YB, Kwak Y-D, Yang Z, Thompson R, Luo Z, et al. Statin's
excitoprotection is mediated by Sapp and the subsequent attenuation of
calpain-induced truncation events, likely via rho-rock signaling. The
Journal of Neuroscience. 2009Sep9;29(36):11226–36.
Perry DC, Sturm VE, Peterson MJ, Pieper CF, Bullock T, Boeve BF, et al.
Association of traumatic brain injury with subsequent neurological and
psychiatric disease: A meta-analysis. Journal of Neurosurgery.
Aug28;124(2):511–26.
Traumatic brain injury (TBI) [Internet]. Alzheimer's Disease and Dementia.
[citado 2023Feb24]. Disponible en: https://www.alz.org/alzheimersdementia/what-is-dementia/related_conditions/traumatic-braininjury#:~:text=The%20key%20studies%20showing%20an,a%204.5%20ti
mes%20greater%20risk
Cuamani MG, García AON. El papel emergente del factor nuclear eritroide
Nrf2 en la neuroprotección mediada por astrocitos. Rev Mex Neuroci.
;17(5):49-59.
Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress,
inflammation, and cancer: How are they linked? Free Radical Biology and
Medicine. 2010Sep16;49(11):1603–16.
Zhang L, Wang H. Targeting the NF-E2-related factor 2 pathway: A novel
strategy for traumatic brain injury. Molecular Neurobiology.
Feb21;55(2):1773–85.
Jin W, Wang H, Yan W, Zhu L, Hu Z, Ding Y, et al. Role of Nrf2 in protection
against traumatic brain injury in mice. Journal of Neurotrauma.
Feb5;26(1):131–9.
Lu X-Y, Wang H-dong, Xu J-G, Ding K, Li T. Pretreatment with tertbutylhydroquinone attenuates cerebral oxidative stress in mice after
traumatic brain injury. Journal of Surgical Research.
May1;188(1):206–12.
Shu L, Wang C, Wang J, Zhang Y, Zhang X, Yang Y, et al. The
neuroprotection of hypoxic preconditioning on rat brain against
traumatic brain injury by up-regulated transcription factor Nrf2 and HO-
expression. Neuroscience Letters. 2016Jan6;611:74–80.
Zhao J, Moore AN, Redell JB, Dash PK (2007) Enhancing expression of Nrf2-
driven genes protects the blood brain barrier afterbrain injury. The
Journal of neuroscience : the official journal of the Society for
Neuroscience 27:10240–10248
Xu J, Wang H, Ding K, Zhang L, Wang C, Li T, Wei W, Lu X (2014) Luteolin
provides neuroprotection in models of traumatic brain injury via the Nrf2-
ARE pathway. Free Radic Biol Med 71: 186–19
National Center for Biotechnology Information. Tert-butylhydroquinone
[Internet]. PubChem Compound Database. U.S. National Library of
Medicine; 2023 [citado 2023Feb23]. Disponible en:
https://pubchem.ncbi.nlm.nih.gov/compound/tert-Butylhydroquinone
Khezerlou A, Akhlaghi Apouya, Alizadeh AM, Dehghan P, Maleki P.
Alarming impact of the excessive use of tert-butylhydroquinone in food
products: A narrative review. Toxicology Reports. 2022May2;9:1066–75.
Tert butylhydroquinone [Internet]. Tert Butylhydroquinone - an overview
| ScienceDirect Topics. 2002 [citado 2023Feb22]. Disponible en:
https://www.sciencedirect.com/topics/medicine-and-dentistry/tertbutylhydroquinone
Jin W, Kong J, Wang H, Wu J, Lu T, Jiang J, et al. Protective effect of tertbutylhydroquinone on cerebral inflammatory response following
traumatic brain injury in mice. Injury. 2011Apr3;42(7):714–8.
Johnson DA, Andrews GK, Xu W, Johnson JA. Activation of the antioxidant
response element in primary cortical neuronal cultures derived from
transgenic reporter mice. Journal of Neurochemistry.
Jun6;81(6):1233–41.
Li J, Johnson D, Calkins M, Wright L, Svendsen C, Johnson J. Stabilization of
NRF2 by TBHQ confers protection against oxidative stress-induced cell
death in human neural stem cells. Toxicological Sciences.
Feb3;83(2):313–28.
Shih AY, Li P, Murphy TH. A small-molecule-inducible NRF2-mediated
antioxidant response provides effective prophylaxis against cerebral
ischemiain vivo. The Journal of Neuroscience. 2005;25(44):10321–35.
Wang Z, Ji C, Wu L, Qiu J, Li Q, Shao Z, et al. Tert-butylhydroquinone
alleviates early brain injury and cognitive dysfunction after experimental
subarachnoid hemorrhage: Role of KEAP1/Nrf2/Are pathway. PLoS ONE.
May21;9(5).
Zhang Z-W, Liang J, Yan J-X, Ye Y-C, Wang J-J, Chen C, et al. TBHQ improved
neurological recovery after traumatic brain injury by inhibiting the
overactivation of astrocytes. Brain Research. 2020;1739:146818.
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