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Traumatic brain injury (TBI) is a complex and progressive brain injury with no approved treatments that needs both short- and long-term therapeutic strategies to cope with the variety of physiopathological mechanisms involved. In particular, neuroinflammation is a key process modulating TBI outcome, and the potentiation of these mechanisms by pro-inflammatory gene therapy vectors could contribute to the injury progression. Here, we evaluate in the controlled cortical impact model of TBI, the safety of integrative-deficient lentiviral vectors (IDLVs) or the non-viral HNRK recombinant modular protein/DNA nanovector. These two promising vectors display different tropisms, transduction efficiencies, short- or long-term transduction or inflammatory activation profile. We show that the brain intraparenchymal injection of these vectors overexpressing green fluorescent protein after a CCI is not neurotoxic, and interestingly, can decrease the short-term sensory neurological deficits, and diminish the brain tissue loss at 90 days post lesion (dpl). Moreover, only IDLVs were able to mitigate the memory deficits elicited by a CCI. These vectors did not alter the microglial or astroglial reactivity at 90 dpl, suggesting that they do not potentiate the on-going neuroinflammation. Taken together, these data suggest that both types of vectors could be interesting tools for the design of gene therapy strategies targeting immediate or long-term neuropathological mechanisms of TBI.
This article was published in the following journal.
Name: Gene therapy
To investigated the long-term effect of childhood Traumatic Brain Injury (TBI) on adulthood Relationship Quality (RQ), examining injury severity, age of injury, and markers of prefrontal cortex (PFC) ...
The response of the developing brain to traumatic injury is different from the response of the mature, adult brain. There are critical developmental trajectories in the young brain, whereby injury can...
To examine the long-term consequences of early childhood traumatic brain injury (TBI), approximately 6.8 years post-injury, on cognitive communication competency within a complex interplay of individu...
To examine long-term outcomes of self-reported physical and mental health among Post-9/11 Veterans stratified by traumatic brain injury (TBI) severity, we hypothesized that more severe TBI would be as...
Traumatic brain injury most commonly affects young adults under the age of 35 and frequently results in reduced quality of life, disability, and death. In long-term survivors, hypopituitarism is a com...
The purpose of this study is to see if the treatment of severely brain injured patients with darbepoetin (a long acting form of erythropoietin) will be safe, and will reduce brain damage b...
This study is a prospective multi-centre randomized trial to compare the effect of long-term mild hypothermia versus routine normothermic intensive management in patients with severe traum...
Many people who have a traumatic brain injury (TBI) - usually from a blow to the head such as in a vehicle collision or in a fall do not survive or, if they do, suffer from long-term disab...
The purpose of this study is to determine the early effects of transcranial direct current stimulation (tDCS) in patients with mild traumatic brain injury and persistent post concussion sy...
Investigators will determine the long-lasting effects of post-acute rehabilitation after traumatic brain injury and stroke. Investigators will also evaluate if the beneficial effects of re...
Prolonged unconsciousness from which the individual cannot be aroused, associated with traumatic injuries to the BRAIN. This may be defined as unconsciousness persisting for 6 hours or longer. Coma results from injury to both cerebral hemispheres or the RETICULAR FORMATION of the BRAIN STEM. Contributing mechanisms include DIFFUSE AXONAL INJURY and BRAIN EDEMA. (From J Neurotrauma 1997 Oct;14(10):699-713)
A form of acquired brain injury which occurs when a sudden trauma causes damage to the brain.
Acute and chronic (see also BRAIN INJURIES, CHRONIC) injuries to the brain, including the cerebral hemispheres, CEREBELLUM, and BRAIN STEM. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with DIFFUSE AXONAL INJURY or COMA, POST-TRAUMATIC. Localized injuries may be associated with NEUROBEHAVIORAL MANIFESTATIONS; HEMIPARESIS, or other focal neurologic deficits.
Traumatic injuries to the cranium where the integrity of the skull is not compromised and no bone fragments or other objects penetrate the skull and dura mater. This frequently results in mechanical injury being transmitted to intracranial structures which may produce traumatic brain injuries, hemorrhage, or cranial nerve injury. (From Rowland, Merritt's Textbook of Neurology, 9th ed, p417)
Bleeding within the brain as a result of penetrating and nonpenetrating CRANIOCEREBRAL TRAUMA. Traumatically induced hemorrhages may occur in any area of the brain, including the CEREBRUM; BRAIN STEM (see BRAIN STEM HEMORRHAGE, TRAUMATIC); and CEREBELLUM.
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Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...
Gene therapy is the use of DNA as a pharmaceutical agent to treat disease. It derives its name from the idea that DNA can be used to supplement or alter genes within an individual's cells as a therapy to treat disease. The most common form of gene th...