Structural and functional characteristic of hippocampal neuronal damage after experimental traumatic brain injury and apoE3 gene therapy
Keywords:traumatic brain injury, hippocampus, ultrastructure, cognitive disorders, gene therapy, apolipoprotein E, experiment
Introduction. The purpose of the study was to estimate the neuronal morphologic changes in hippocampus and its functional characteristics after experimental severe traumatic brain injury (TBI), and the possibilities of such disorders correction by means of gene therapy that launches the synthesis of epsilon 3 isoform of apolipoprotein E in brain tissue.
Materials and methods. Severe diffuse TBI in rats was modeled under overall anesthesia by free load weighing 450 g, falling from a 1.5 m elevation. The mixture of DOTAP liposome and 25 µg of plasmid vector pCMV•SPORT6 with cDNA of apoE3 gene was infused intraventricularly using ALZET osmotic pumps.
Results. Severe TBI is characterized by the neuronal depopulation of hippocampus, damage to its cytoarchitectonics with considerable changes of neuronal qualitative characteristics including the increased proportion of destructively changed cells. It is accompanied by profound cognitive deficits, particularly persistent anterograde amnesia which is characterized by posttraumatic decrease of spatial memory and learning. The liposome-mediated brain tissue transfection with plasmid vector carrying the gene of epsilon 3 isoform of apolipoprotein E diminishes the depth and extent of secondary injury of hippocampal neurons, preserves hippocampal cytoarchitectonics and facilitates the speedy recovery of posttraumatic cognitive deficits.
Conclusion. Gene therapy has therapeutic potential in treatment of severe TBI.
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Copyright (c) 2012 Vadym Biloshytsky, Sergey Mikhalsky, Nina Gridina, Tatyana Kvitnitskaya-Ryzhova, Eugene Pedachenko
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