The influence of gene therapy on structural damage in case of traumatic brain injury in experiment
DOI:
https://doi.org/10.25305/unj.108807Keywords:
traumatic brain injury, gene therapy, apolipoprotein E, plasmid vector, cationic liposomeAbstract
Possibilities of improving traumatic brain injury (TBI) outcomes using gene therapy directed at apoE3 synthesis induction in damaged brain tissue were studied in an experimental setting. A severe TBI was inflicted in rats under general anesthesia by a450 gweight falling free from a height of1.5 m. A mixture of DOTAP liposome and 25 µg of plasmid vector pCMV•SPORT6 with cDNA of APOE3 gene was infused into ventricles using ALZET pumps. On the 10th day following the TBI the transfection effectiveness was evaluated using RT-PCR; histological examination of the brain tissue was done. Applying the RT-PCR method corroborated the expression of APOE3 gene with corresponding mRNA presence in the samples of brain tissue. Liposome transfection of the rats’ damaged brain by APOE3 protected the vascular system and brain parenchyma, and prevented the formation of secondary disintegration zones in the damaged brain. It was verified by a considerable reduction of signs of capillary permeability disturbance (almost to marks) and brain parenchyma damage, as well as reactive brain edema in animals under treatment.
References
Белошицкий В.В. Основные направления применения генной терапии при черепно-мозговой травме // Вісн. Укр. товариства генетиків і селекціонерів. — 2005. — Т.3, №1–2. — С.15–20.
Белошицкий В.В., Педаченко Е.Г., Гридина Н.Я. и др. Генная терапия с использованием гена АРОЕ3 как метод коррекции посттравматических когнитивных нарушений в эксперименте // Матеріали IV з’їзду нейрохірургів України. — Дніпропетровськ, 2008. — С.204.
Педаченко Е.Г., Белошицкий В.В., Васильева И.Г. Аполипопротеин Е: физиологическая роль и возможная терапевтическая эффективность при черепно-мозговой травме // Нейрохирургия. — 2003. — №1. — С.59–65.
Biloshytsky V., Pedachenko E., Kvitnitskaya-Ryzhova T. et al. The effect of cationic liposome-mediated APOE3 in vivo gene transfer on hippocampal morphology and cognitive status following traumatic brain injury in rats: Abstracts of XVIth Annual Congress of the European Society of Gene and Cell Therapy, Brugge (Belgium, November 13–16, 2008)// — Hum. Gene Ther. — 2008. — V.19, N10. — P.1126.
Biloshytsky V.V., Pedachenko E.G., Kvitnitskaya-Ryzhova T.Yu., Mikhalsky S.A. Cationic liposome-mediated APOE3 gene therapy attenuates cognitive impairment following traumatic brain injury in rats // Proceedings of the conference «Mental recovery after traumatic brain injury: a multidisciplinary approach». —Moscow, 2008. — P.24.
Chen X. Glucocorticoids aggravate retrograde memory deficiency associated with traumatic brain injury in rats // J. Neurotrauma. — 2009. — V.26. — P.253–260.
Chen Y., Lomnitski L., Michaelson D.M., Shohami E. Motor and cognitive deficits in apolipoprotein E-deficient mice after closed head injury // Neuroscience. — 1997. — V.80, N4. — P.1255–1262.
Chopp M., Chan P.H., Hsu C.Y. et al. DNA damage and repair in central nervous system injury: National institute of neurological disorders and stroke workshop summary // Stroke. — 1996. — V.27, N3. — P.363–369.
Clark R.S., Chen J.,WatkinsS.C.et al.Apoptosis-suppressor gene bcl-2 expression after traumatic brain injury in rats // J. Neurosci. — 1997. — V.17, N23. — P.9172–9182.
Conti A.C., Raghupathi R., Trojanowski J.Q., McIntosh T.K. Experimental brain injury induces regionally distinct apoptosis during the acute and delayed post-traumatic period // J. Neurosci. — 1998. — V.18, N15. — P.5663–5672.
Doll H. Pharyngeal selective brain cooling improves neurofunctional and neurocognitive outcome after fluid percussion brain injury in rats // J. Neurotrauma. — 2009. — V.26. — P.235–242.
Jenkins L.W., Lu Y.-C., Johnston W.E. et al. Combined therapy affects outcomes differentially after mild traumatic brain injury and secondary forebrain ischemia in rats // Brain Res. — 1999. — V.817. — P.132–144.
Jia F. Effect of post-traumatic mild hypothermia on hippocampal cell death after traumatic brain injury in rats // J. Neurotrauma. — 2009. — V.26. — P.243–252.
Kaya S.S., Mahmood A., Li Y. et al. Apoptosis and expression of p53 response proteins and cyclin D1 after cortical impact in rat brain // Brain Res. — 1999. — V.818, N1. — P.23–33.
Kim B.-T., Rao V.L.R., Sailor K.A. et al. Protective effects of glial cell line-derived neurotrophic factor on hippocampal neurons after TBI // J. Neurosurg. — 2001. — V.95, N4. — P.674–679.
Kotapka M.J., Graham D.I., Adams J.H. et al. Hippocampal pathology in fatal human head injury without high intracranial pressure// J. Neurotrauma. — 1994. — V.11. — P.317–324.
LeVine S.M., Wetzel D.L. In situ chemical analyses from frosen tissue sections by Fourier transform infrared microspectroscopy: Examination of white matter exposed to extravasated blood in the rat brain // Am. J. Pathol. — 1994. — V.145. — P.1041–1047.
Levin H.S. Neurobehavioral outcome of closed head injury: implications for clinical trials // Traumatic brain injury: bioscience and mechanics / Eds. F.A. Bandak, R.H. Eppinger, A.K. Ommaya. —Larchmont,N.Y.: Mary Ann Liebert, 1996. — P.105.
Lynch J.R., Pineda J.A., Morgan D. et al. Apolipoprotein E affects the central nervous system response to injury and the development of cerebral edema // Ann. Neurol. — 2002. — V.51, N1. — P.113–117.
Marmarou A., Foda M.A., van den Brink W. et al. A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics // J. Neurosurg. — 1994. — V.80. — P.291–300.
Philips M.F., Mattiasson G., Wieloch T. et al. Neuroprotective and behavioral efficacy of nerve growth factor-transfected hippocampal progenitor cell transplants after experimental traumatic brain injury // J. Neurosurg. — 2001. — V.94, N5. — P.765–774.
Pohl D., Bittigau P., Ishimaru M.J. et al. N-Methyl-D-aspartate antagonists and apoptotic cell death triggered by head trauma in developing rat brain // Proc. Natl. Acad. Sci. USA. — 1999. — V.96, N5. — P.2508–2513.
Runnerstam M., Bao F., Huang Y. et al. A new model for diffuse brain injury by rotational acceleration: II. Effects on extracellular glutamate, intracranial pressure, and neuronal apoptosis // J. Neurotrauma. — 2001. — V.18, N3. — P.259–273.
Sahuquillo J., Poca M.A., Amoros S. Current aspects of pathophysiology and cell dysfunction after severe head injury // Curr. Pharm. Des. — 2001. — V.7, N15. — P.1475–1503.
Sinson G., Voddi M., McIntosh T.K. Combined fetal neural transplantation and nerve growth factor infusion: effects on neurological outcome following fluid-percussion brain injury in the rat // Neurosurg. Focus. — 1999. — V.7, N3. — Article 3.
Springer J.E., Nottingham S.A., McEwen M.L. et al. Caspase-3 apoptotic signaling following injury to the central nervous system // Clin. Chem. Lab. Med. — 2001. — V.39, N4. — P.299–307.
Yakovlev A.G., Knoblach S.M., Fan L. et al. Activation of CPP32-like caspases contributes to neuronal apoptosis and neurological dysfunction after traumatic brain injury // J. Neurosci. — 1997. — V.17, N19. — P.7415–7424.
Yang X.Y., Yang S.Y., Zhang J.N., Xue L. Experimental study on expression and activation of caspase-3 after acute brain trauma // Proceedings 12th World Congress of Neurosurgery. — 2001. — P.155–157.
Zola-Morgan S., Squire L.R., Amaral D.G. Human amnesia and the medial temporal region: enduring memory impairment following a bilateral lesion limited to field CA1 on the hippocampus // J. Neurosci. — 1986. — V.6. — P.2950–2967.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2009 V. V. Biloshytsky, V. M. Semenova, N. Ya. Gridina, L. O. Tsyba, I. G. Vasilyeva, N. G. Chopik
This work is licensed under a Creative Commons Attribution 4.0 International License.
Ukrainian Neurosurgical Journal abides by the CREATIVE COMMONS copyright rights and permissions for open access journals.
Authors, who are published in this Journal, agree to the following conditions:
1. The authors reserve the right to authorship of the work and pass the first publication right of this work to the Journal under the terms of Creative Commons Attribution License, which allows others to freely distribute the published research with the obligatory reference to the authors of the original work and the first publication of the work in this Journal.
2. The authors have the right to conclude separate supplement agreements that relate to non-exclusive work distribution in the form of which it has been published by the Journal (for example, to upload the work to the online storage of the Journal or publish it as part of a monograph), provided that the reference to the first publication of the work in this Journal is included.