Browsing by Subject "Brain / drug effects"
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Item Current Strategies for Brain Drug Delivery(Ivyspring International Publisher, 2018-02-05) Dong, XiaoweiThe blood-brain barrier (BBB) has been a great hurdle for brain drug delivery. The BBB in healthy brain is a diffusion barrier essential for protecting normal brain function by impeding most compounds from transiting from the blood to the brain; only small molecules can cross the BBB. Under certain pathological conditions of diseases such as stroke, diabetes, seizures, multiple sclerosis, Parkinson's disease and Alzheimer disease, the BBB is disrupted. The objective of this review is to provide a broad overview on current strategies for brain drug delivery and related subjects from the past five years. It is hoped that this review could inspire readers to discover possible approaches to deliver drugs into the brain. After an initial overview of the BBB structure and function in both healthy and pathological conditions, this review re-visits, according to recent publications, some questions that are controversial, such as whether nanoparticles by themselves could cross the BBB and whether drugs are specifically transferred to the brain by actively targeted nanoparticles. Current non-nanoparticle strategies are also reviewed, such as delivery of drugs through the permeable BBB under pathological conditions and using non-invasive techniques to enhance brain drug uptake. Finally, one particular area that is often neglected in brain drug delivery is the influence of aging on the BBB, which is captured in this review based on the limited studies in the literature.Item The Long-Term Neurodegenerative Effects of Repetitive Mild Traumatic Brain Injury and Treatment With Sigma-1 Receptor Agonist PRE-084(2021-05) Abad-Jacobi, Christopher; Schreihofer, Derek A.; Sumien, Nathalie; Schreihofer, Ann M.An estimated 1.6 – 3.8 million sports-related traumatic brain injuries (TBI) occur every year in the U.S. Recent retrospective studies suggest that repetitive mild TBI (rmTBI) is associated with the earlier onset of neurodegenerative diseases. Mild TBI can be hard to detect, and there are currently no widely accepted biomarkers that could aid in the diagnosis of mTBI. Further, there is currently no standard pharmacological treatment for TBI. Our previous work demonstrated neurological deficits 1 week following 20-25 rmTBI in young male mice. We hypothesized that some of these deficits would persist up to 5-15 weeks following injury and that treatment with an agonist of the Sigma-1 receptor (PRE-084) could reduce these deficits, as has been demonstrated in other neurodegenerative models. Eight-week-old male C57BK6 mice were divided into sham injury + Vehicle, rmTBI + Vehicle, and rmTBI+PRE084 groups (n=10/gp). Mice were lightly anesthetized with isoflurane and administered either PRE084 (1mg/kg sc or ip) or vehicle immediately prior to experiencing closed head-injury with rotational acceleration via a 65g weight drop 5 days a week for 5 weeks. Five (group 1) and fifteen weeks (group 2) after the final injury mice were assessed for neurological deficits. Injured mice in test 1 demonstrated significant (P<0.05) deficits in motor and vestibular-motor. Wake times were significantly increased (P<0.05) for Hit mice in both tests one and two. However, cognitive performance in T-maze active avoidance, anxiety-related behavior in the elevated plus maze, and Water Maze on group 1 were not affected. Water maze data on group 2 yielded significant results (P<0.05) indicating both groups of Hit mice performed worse on percent time in annulus 40 centimeters, and on path length in trials one and three. Treatment with PRE-084 did not ameliorate any of these deficits. On group 2, Hit + PRE-084 mice performed significantly worse than their counterparts on the rotarod test. The data suggest that there are some chronic deficits for at least 5 weeks after rmTBI, and that sigma-1 activation does not reverse negative effects of rmTBI. Ongoing studies are examining the persistence of these deficits in mice 15 weeks after the final injury, which are relevant to rmTBI related deficits in military personnel that persist up to a year. Water maze data is beginning to persistent deficits due to rmTBI in the long-term.