Publicaciones por año
Publicaciones del Departamento de Histología y Embriología
Bardet-Biedl syndrome: Is it only cilia dysfunction?
FEBS Lett 2015 589(22):3479-91
Rossina Novas 1 , Magdalena Cardenas-Rodriguez 1 , Florencia Irigoín 2 , Jose L Badano 3
1 Human Molecular Genetics Laboratory, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo CP11400, Uruguay. 2 Human Molecular Genetics Laboratory, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo CP11400, Uruguay; Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Gral. Flores 2125, Montevideo CP11800, Uruguay. 3 Human Molecular Genetics Laboratory, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo CP11400, Uruguay
DOI: 10.1016/j.febslet.2015.07.031
PMID: 26231314
Pubmed: https://pubmed.ncbi.nlm.nih.gov/26231314
Texto completo: https://onlinelibrary.wiley.com/doi/10.1016/j.febslet.2015.07.031
Abstract:
Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, pleiotropic disorder, characterized by both congenital and late onset defects. From the analysis of the mutational burden in patients to the functional characterization of the BBS proteins, this syndrome has become a model for both understanding oligogenic patterns of inheritance and the biology of a particular cellular organelle: the primary cilium. Here we briefly review the genetics of BBS to then focus on the function of the BBS proteins, not only in the context of the cilium but also highlighting potential extra-ciliary roles that could be relevant to the etiology of the disorder. Finally, we provide an overview of how the study of this rare syndrome has contributed to the understanding of cilia biology and how this knowledge has informed on the cellular basis of different clinical manifestations that characterize BBS and the ciliopathies.
Defective Human Sperm Cells Are Associated with Mitochondrial Dysfunction and Oxidant Production
Biol Reprod 2015 93(5):119
Adriana Cassina 1 , Patricia Silveira 2 , Lidia Cantu 3 , Jose Maria Montes 3 , Rafael Radi 1 , Rossana Sapiro 4
1 Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay Centro de Investigaciones Biomédicas (CEINBIO), Universidad de la República, Montevideo, Uruguay. 2 Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay Centro de Investigaciones Biomédicas (CEINBIO), Universidad de la República, Montevideo, Uruguay. 3 Andrology Clinic Fertilab, Montevideo, Uruguay. 4 Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay Centro de Investigaciones Biomédicas (CEINBIO), Universidad de la República, Montevideo, Uruguay
DOI: 10.1095/biolreprod.115.130989
PMID: 26447142
Pubmed: https://pubmed.ncbi.nlm.nih.gov/26447142
Texto completo: https://academic.oup.com/biolreprod/article-lookup/doi/10.1095/biolreprod.115.130989
Abstract:
Infertility affects about 15% of couples of reproductive age. The male factor is involved in nearly 50% of infertility cases. Defective human sperm function has been associated with evidence of high levels of reactive oxygen species (ROS) and a resultant loss of fertilizing potential in vivo and in vitro. Analogous to what has been observed in somatic cells, mitochondria are likely the major sources of ROS in sperm cells. In this study, we analyzed mitochondrial function using high-resolution respirometry, ROS production, and footprints of oxidative and nitrative stress processes in intact human sperm cells. We showed that mitochondrial dysfunction (measured through the respiratory control ratio) was correlated with a decrease in human sperm motility. The samples analyzed presented nitro-oxidative modifications of proteins, such as protein 3-nitrotyrosine, that were observed mainly in the mid-piece (where mitochondria are localized) and in the sperm head. Semen samples presenting lower percentage of motile sperm showed higher amounts of nitro-oxidative protein modifications than those with larger quantities of motile sperm. When spermatozoa were exposed to inhibitors of the respiratory mitochondrial function, in the presence of a nitric oxide flux, sperm produced potent nitro-oxidative species (i.e., peroxynitrite). This effect was observed in more than 90% of intact living sperm cells and in sperm mitochondrial fractions. These data suggest that dysfunctional mitochondria in sperm cells produce oxidants that may contribute to male infertility. These data provide the rationale for testing the potential of compounds that improve sperm mitochondrial function to treat male infertility.
The secretogranin-II derived peptide secretoneurin modulates electric behavior in the weakly pulse type electric fish, Brachyhypopomus gauderio
Gen Comp Endocrinol 2015 222:158-66
Paula Pouso 1 , Laura Quintana 2 , Gabriela C López 3 , Gustavo M Somoza 3 , Ana C Silva 4 , Vance L Trudeau 5
1 Depto Histología y Embriología, Facultad de Medicina, Universidad de la República, 11800 Montevideo, Uruguay; Unidad Bases Neurales de la Conducta, Departamento de Neurofisiología Celular y Molecular, IIBCE, 11600 Montevideo, Uruguay. 2 Unidad Bases Neurales de la Conducta, Departamento de Neurofisiología Celular y Molecular, IIBCE, 11600 Montevideo, Uruguay. 3 Laboratorio de Ictiofisiología y Acuicultura, Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús (IIBINTECH), Provincia de Buenos Aires, Argentina. 4 Unidad Bases Neurales de la Conducta, Departamento de Neurofisiología Celular y Molecular, IIBCE, 11600 Montevideo, Uruguay; Laboratorio de Neurociencias, Facultad de Ciencias, Universidad de la República, 11400 Montevideo, Uruguay. 5 Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
DOI: 10.1016/j.ygcen.2015.06.015
PMID: 26141148
Pubmed: https://pubmed.ncbi.nlm.nih.gov/26141148
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S0016-6480(15)00183-5
Abstract:
Secretoneurin (SN) in the preoptic area and pituitary of mammals and fish has a conserved close association with the vasopressin and oxytocin systems, members of a peptide family that are key in the modulation of sexual and social behaviors. Here we show the presence of SN-immunoreactive cells and projections in the brain of the electric fish, Brachyhypopomus gauderio. Secretoneurin colocalized with vasotocin (AVT) and isotocin in cells and fibers of the preoptic area. In the rostral pars distalis of the pituitary, many cells were both SN and prolactin-positive. In the hindbrain, at the level of the command nucleus of the electric behavior (pacemaker nucleus; PN), some of SN-positive fibers colocalized with AVT. We also explored the potential neuromodulatory role of SN on electric behavior, specifically on the rate of the electric organ discharge (EOD) that signals arousal, dominance and subordinate status. Each EOD is triggered by the command discharge of the PN, ultimately responsible for the basal EOD rate. SN modulated diurnal basal EOD rate in freely swimming fish in a context-dependent manner; determined by the initial value of EOD rate. In brainstem slices, SN partially mimicked the in vivo behavioral effects acting on PN firing rate. Taken together, our results suggest that SN may regulate electric behavior, and that its effect on EOD rate may be explained by direct action of SN at the PN level through either neuroendocrine and/or endocrine mechanisms.
Spatial and temporal distribution of Patched-related protein in the Drosophila embryo
Gene Expr Patterns 2015 19(1-2):120-8
Carmen Bolatto 1 , Cristina Parada 2 , Fiorella Revello 3 , Alejandro Zuñiga 4 , Pablo Cabrera 5 , Verónica Cambiazo 6
1 Laboratorio de Biología del Desarrollo, Departamento de Histología y Embriología, Facultad de Medicina-Universidad de la República, Montevideo, Uruguay. Electronic address: cbolatto@fmed.edu.uy. 2 Laboratorio de Biología del Desarrollo, Departamento de Histología y Embriología, Facultad de Medicina-Universidad de la República, Montevideo, Uruguay. Electronic address: cristinap@fmed.edu.uy. 3 Laboratorio de Biología del Desarrollo, Departamento de Histología y Embriología, Facultad de Medicina-Universidad de la República, Montevideo, Uruguay. Electronic address: fiorev85@gmail.com. 4 Laboratorio de Bioinformática y Expresión Génica, INTA-Universidad de Chile and Fondap Center for Genome Regulation (CGR), Santiago, Chile. Electronic address: jano@inta.uchile.cl. 5 Laboratorio de Bioinformática y Expresión Génica, INTA-Universidad de Chile and Fondap Center for Genome Regulation (CGR), Santiago, Chile. 6 Laboratorio de Bioinformática y Expresión Génica, INTA-Universidad de Chile and Fondap Center for Genome Regulation (CGR), Santiago, Chile. Electronic address: vcambiaz@inta.cl.
DOI: 10.1016/j.gep.2015.10.002
PMID: 26506022
Pubmed: https://pubmed.ncbi.nlm.nih.gov/26506022
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S1567-133X(15)30013-2
Abstract:
Patched-related (Ptr) encodes a protein with 12 potential transmembrane domains and a sterol-sensing domain that is closely related in predicted topology and domain organization to Patched, the canonical receptor of the Hedgehog pathway. Here we describe the production of an antibody specific for Drosophila Ptr and analyse its spatial and temporal distribution in the embryo. We find that at early developmental stages Ptr is predominantly localized at cell periphery but later on it becomes strongly and almost exclusively expressed in hemocytes. Interestingly Ptr null mutant embryos died without hatching. Our findings suggest that Ptr plays an essential function in Drosophila development, perhaps as a new receptor of embryonic hemocytes.
CD300f immunoreceptor contributes to peripheral nerve regeneration by the modulation of macrophage inflammatory phenotype
J Neuroinflammation 2015 12:145
Hugo Peluffo 1 2 , Patricia Solari-Saquieres 3 , Maria Luciana Negro-Demontel 4 , Isaac Francos-Quijorna 5 , Xavier Navarro 6 , Ruben López-Vales 7 , Joan Sayós 8 , Natalia Lago 9 10
1 Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur Montevideo, Mataojo 2020, CP 11400, Montevideo, Uruguay. Hugo.peluffo@pasteur.edu.uy. 2 Department of Histology and Embryology, Faculty of Medicine, UDELAR, Montevideo, Uruguay. Hugo.peluffo@pasteur.edu.uy. 3 Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur Montevideo, Mataojo 2020, CP 11400, Montevideo, Uruguay. patricia.solari08@gmail.com. 4 Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur Montevideo, Mataojo 2020, CP 11400, Montevideo, Uruguay. luchanegro@gmail.com. 5 Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain. isaac.francos@uab.cat. 6 Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain. Xavier.Navarro@uab.es. 7 Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain. ruben.lopez@uab.cat. 8 Immunobiology Group, CIBBIM-Nanomedicine Program, Hospital Universitari Vall d'Hebron, Institut de Recerca (VHIR), Universitat Autonoma de Barcelona, Barcelona, Spain. joan.sayos@vhir.org. 9 Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur Montevideo, Mataojo 2020, CP 11400, Montevideo, Uruguay. nlago@pasteur.edu.uy. 10 Neurodegeneration Laboratory, Institut Pasteur Montevideo, Montevideo, Uruguay. nlago@pasteur.edu.uy.
DOI: 10.1186/s12974-015-0364-y
PMID: 26259611
Pubmed: https://pubmed.ncbi.nlm.nih.gov/26259611
Texto completo: https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-015-0364-y
Abstract:
Background: It has recently become evident that activating/inhibitory cell surface immune receptors play a critical role in regulating immune and inflammatory processes in the central nervous system (CNS). The immunoreceptor CD300f expressed on monocytes, neutrophils, and mast cells modulates inflammation, phagocytosis, and outcome in models of autoimmune demyelination, allergy, and systemic lupus erythematosus. On the other hand, a finely regulated inflammatory response is essential to induce regeneration after injury to peripheral nerves since hematogenous macrophages, together with resident macrophages and de-differentiated Schwann cells, phagocyte distal axonal and myelin debris in a well-orchestrated inflammatory response. The possible roles and expression of CD300f and its ligands have not been reported under these conditions.
Neonatal testosterone exposure induces early development of follicular cysts followed by sympathetic ovarian hyperinnervation
Reprod Fertil Dev 2015 28(11) 1753-1761
Gabriel Anesetti, Rebeca Chávez-Genaro
Histology and Embryology Department, School of Medicine, General Flores 2125, CP 11800, Montevideo, Uruguay
DOI: 10.1071/RD14460
PMID: 25989716
Pubmed: https://pubmed.ncbi.nlm.nih.gov/25989716
Texto completo: https://www.publish.csiro.au/rd/RD14460
Abstract:
This study analysed the temporal association between ovarian cyst development induced by neonatal androgenisation and sympathetic innervation. Neonatal rats (postnatal Days 1 to 5) were treated with testosterone or dihydrotestosterone and the effects were evaluated at postnatal Days 20, 40, 90 or 180. Ovulation rate, number of cystic follicles and density of sympathetic fibres were analysed. The effects of surgical denervation or gonadotrophin stimulation were also assessed. Rats exposed to testosterone showed no oestrous cycle activity and did not ovulate, maintaining a polycystic ovarian morphology at all ages studied. Also, a significant increase in ovarian density of noradrenergic fibres was detected at postnatal Days 90 and 180. Sympathectomy was unable to re-establish ovarian activity; however, human chorionic gonadotrophin stimulation was enough to induce ovulation. The impact of dihydrotestosterone on ovarian function was less noticeable, showing the coexistence of corpora lutea and cystic structures without changes in sympathetic innervation. Our findings suggest that a remodelling of ovarian sympathetic innervation occurs as a response to modifications in the pattern of follicular growth induced by testosterone. A role of sympathetic innervation in the maintenance of the polycystic condition is suggested.
The Receptor CMRF35-Like Molecule-1 (CLM-1) Enhances the Production of LPS-Induced Pro-Inflammatory Mediators during Microglial Activation
PLoS One 2015 10(4):e0123928
Aroa Ejarque-Ortiz 1 , Carme Solà 2 , Águeda Martínez-Barriocanal 1 , Simó Schwartz Jr 3 , Margarita Martín 4 , Hugo Peluffo 5 , Joan Sayós 1
1 Immunobiology Group, CIBBIM-Nanomedicine Program, Hospital Universitari Vall d'Hebrón, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBBER-BBN), Instituto de Salud Carlos III, Barcelona, Spain. 2 Department of Cerebral Ischemia and Neurodegeneration, Institut d'Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones Científicas (CSIC), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. 3 Drug Delivery and Targeting Group, CIBBIM-Nanomedicine Program, Hospital Universitari Vall d'Hebrón, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBBER-BBN), Instituto de Salud Carlos III, Barcelona, Spain. 4 Biochemistry Unit, Faculty of Medicine, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain. 5 Neurodegeneration Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay; Department of Histology and Embryology, Faculty of Medicine, UDELAR, Montevideo, Uruguay.
DOI: 10.1371/journal.pone.0123928
PMID: 25927603
Pubmed: https://pubmed.ncbi.nlm.nih.gov/25927603
Texto completo: https://dx.plos.org/10.1371/journal.pone.0123928
Abstract:
CMRF35-like molecule-1 (CLM-1) belongs to a receptor family mainly expressed in myeloid cells that include activating and inhibitory receptors. CLM-1 contains two ITIMs and a single immunoreceptor tyrosine-based switch motif (ITSM), although also displays a binding site for p85α regulatory subunit of PI3K. By using murine primary microglial cultures, we show the presence of all CLM members in microglial cells and characterize the expression of CLM-1 both in basal conditions and during microglial activation. The TLR4 agonist lipopolysaccharide (LPS) and the TLR3 agonist polyinosinic-polycytidylic acid (Poly I:C) induce an increase in microglial CLM-1 mRNA levels in vitro, whereas the TLR2/6 heterodimer agonist peptidoglycan (PGN) produces a marked decrease. In this study we also describe a new soluble isoform of CLM-1 that is detected at mRNA and protein levels in basal conditions in primary microglial cultures. Interestingly, CLM-1 engagement enhances the transcription of the pro-inflammatory mediators TNFα, COX-2 and NOS-2 in microglial cells challenged with LPS. These results reveal that CLM-1 can acts as a co-activating receptor and suggest that this receptor could play a key role in the regulation of microglial activation.
BBB-targeting, protein-based nanomedicines for drug and nucleic acid delivery to the CNS
Biotechnol Adv 2015 33(2):277-87
Hugo Peluffo 1 , Ugutz Unzueta 2 , María Luciana Negro-Demontel 1 , Zhikun Xu 2 , Esther Váquez 2 , Neus Ferrer-Miralles 2 , Antonio Villaverde 2
1 Neuroinflammation Gene Therapy Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay; Departamento de Histología y Embriología, Facultad de Medicina, Universidad de la República (UDELAR), Montevideo, Uruguay. 2 Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain; Department de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain; CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Bellaterra, 08193 Barcelona, Spain.
DOI: 10.1016/j.biotechadv.2015.02.004
PMID: 25698504
Pubmed: https://pubmed.ncbi.nlm.nih.gov/25698504
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S0734-9750(15)00029-4
Abstract:
The increasing incidence of diseases affecting the central nervous system (CNS) demands the urgent development of efficient drugs. While many of these medicines are already available, the Blood Brain Barrier and to a lesser extent, the Blood Spinal Cord Barrier pose physical and biological limitations to their diffusion to reach target tissues. Therefore, efforts are needed not only to address drug development but specially to design suitable vehicles for delivery into the CNS through systemic administration. In the context of the functional and structural versatility of proteins, recent advances in their biological fabrication and a better comprehension of the physiology of the CNS offer a plethora of opportunities for the construction and tailoring of plain nanoconjugates and of more complex nanosized vehicles able to cross these barriers. We revise here how the engineering of functional proteins offers drug delivery tools for specific CNS diseases and more transversally, how proteins can be engineered into smart nanoparticles or 'artificial viruses' to afford therapeutic requirements through alternative administration routes.
Morphological evaluation of sperm from infertile men selected by magnetic activated cell sorting (MACS)
Reprod Biol 2014 14(4):289-92
Gianni Curti 1 , Fernanda Skowronek 2 , Rita Vernochi 3 , Ana Laura Rodriguez-Buzzi 4 , Juan Carlos Rodriguez-Buzzi 5 , Gabriela Casanova 6 , Rossana Sapiro 7
1 Departamento de Biologia Molecular - Instituto De Investigaciones Biológicas Clemente Estable (IIBCE), Avenida Italia 3318, CP 11600 Montevideo, Uruguay. Electronic address: giannicurti@gmail.com. 2 Laboratorio de Biología Molecular de la Reproducción - Departamento de Histología y Embriología, Facultad de Medicina, Gral. Flores 2125, 11800 Montevideo, Uruguay. Electronic address: fernandaskowronek@gmail.com. 3 Centro de Reproducción Humana del Interior (CERHIN), Bvar. Artigas 1665/102, Montevideo, Uruguay. Electronic address: draritaverno@gmail.com. 4 Centro de Reproducción Humana del Interior (CERHIN), Bvar. Artigas 1665/102, Montevideo, Uruguay. Electronic address: anucharod@gmail.com. 5 Centro de Reproducción Humana del Interior (CERHIN), Bvar. Artigas 1665/102, Montevideo, Uruguay. Electronic address: jcrbuzzi@gmail.com. 6 Unidad de Microscopía Electrónica de Transmisión - Facultad de Ciencias, Iguá 4225, 11400 Montevideo, Uruguay. Electronic address: paragaby@gmail.com. 7 Laboratorio de Biología Molecular de la Reproducción - Departamento de Histología y Embriología, Facultad de Medicina, Gral. Flores 2125, 11800 Montevideo, Uruguay. Electronic address: rsapiro@fmed.edu.uy.
DOI: 10.1016/j.repbio.2014.07.002
PMID: 25454495
Pubmed: https://pubmed.ncbi.nlm.nih.gov/25454495
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S1642-431X(14)00074-6
Abstract:
Electron microscopy analysis performed in five infertile human subjects after sperm selection by swim-up followed by magnetic activated cell sorting (MACS) demonstrated a decrease in the number of spermatozoa with characteristics compatible with cell death. However, no significant differences were found when the swim-up/MACS semen fraction was compared with swim-up fraction alone.
Comparative analysis of lentiviral vectors and modular protein nanovectors for traumatic brain injury gene therapy
ol Ther Methods Clin Dev 2014 1:14047.
María Luciana Negro-Demontel 1 , Paolo Saccardo 2 , Cecilia Giacomini 3 , Rafael Joaquín Yáñez-Muñoz 4 , Neus Ferrer-Miralles 2 , Esther Vazquez 2 , Antonio Villaverde 2 , Hugo Peluffo 1
1 Neuroinflammation and Gene Therapy Laboratory, Institut Pasteur de Montevideo , Montevideo, Uruguay ; Departmento de Histología y Embriología, Facultad de Medicina, UDELAR , Montevideo, Uruguay. 2 Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona , Barcelona, Spain ; Department de Genètica i de Microbiologia, Universitat Autònoma de Barcelona , Barcelona, Spain ; CIBER en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) , Barcelona, Spain. 3 Cátedra de Bioquímica, Departamento de Biociencias, Facultad de Química, UDELAR , Montevideo, Uruguay. 4 Royal Holloway University of London , Egham, UK.
DOI: 10.1038/mtm.2014.47
PMID: 26015985
Pubmed: https://pubmed.ncbi.nlm.nih.gov/26015985
Texto completo: https://linkinghub.elsevier.com/retrieve/pii/S2329-0501(16)30115-2
Abstract:
Traumatic brain injury (TBI) remains as one of the leading causes of mortality and morbidity worldwide and there are no effective treatments currently available. Gene therapy applications have emerged as important alternatives for the treatment of diverse nervous system injuries. New strategies are evolving with the notion that each particular pathological condition may require a specific vector. Moreover, the lack of detailed comparative studies between different vectors under similar conditions hampers the selection of an ideal vector for a given pathological condition. The potential use of lentiviral vectors versus several modular protein-based nanovectors was compared using a controlled cortical impact model of TBI under the same gene therapy conditions. We show that variables such as protein/DNA ratio, incubation volume, and presence of serum or chloroquine in the transfection medium impact on both nanovector formation and transfection efficiency in vitro. While lentiviral vectors showed GFP protein 1 day after TBI and increased expression at 14 days, nanovectors showed stable and lower GFP transgene expression from 1 to 14 days. No toxicity after TBI by any of the vectors was observed as determined by resulting levels of IL-1β or using neurological sticky tape test. In fact, both vector types induced functional improvement per se.