DOI: https://doi.org/10.25305/unj.108807

The influence of gene therapy on structural damage in case of traumatic brain injury in experiment

V. V. Biloshytsky, V. M. Semenova, N. Ya. Gridina, L. O. Tsyba, I. G. Vasilyeva, N. G. Chopik

Abstract


Possibilities of improving traumatic brain injury (TBI) outcomes using gene therapy directed at apoE3 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.


Keywords


traumatic brain injury; gene therapy; apolipoprotein E; plasmid vector; cationic liposome

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.


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Copyright (c) 2009 V. V. Biloshytsky, V. M. Semenova, N. Ya. Gridina, L. O. Tsyba, I. G. Vasilyeva, N. G. Chopik

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