- Department of Neurosurgery, Geffen School of Medicine at UCLA, Los Angeles, CA, USA
Jason S. Hauptman
Department of Neurosurgery, Geffen School of Medicine at UCLA, Los Angeles, CA, USA
DOI:10.4103/2152-7806.101002Copyright: © 2012 Everson R. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
How to cite this article: Everson R, Hauptman JS. From the bench to the bedside: Brain–machine interfaces in spinal cord injury, the blood–brain barrier, and neurodegeneration, using the hippocampus to improve cognition, metabolism, and epilepsy, and understanding axonal death. Surg Neurol Int 13-Sep-2012;3:108
How to cite this URL: Everson R, Hauptman JS. From the bench to the bedside: Brain–machine interfaces in spinal cord injury, the blood–brain barrier, and neurodegeneration, using the hippocampus to improve cognition, metabolism, and epilepsy, and understanding axonal death. Surg Neurol Int 13-Sep-2012;3:108. Available from: http://sni.wpengine.com/surgicalint_articles/from-the-bench-to-the-bedside-brain-machine-interfaces-in-spinal-cord-injury-the-blood-brain-barrier-andneurodegeneration-using-the-hippocampus-to-improve-cognition-metabolism-a/
Improving cognitive impairment by decreasing hippocampal hyeractivity. New brain-machine interfaces for restoring neurologic function. Reversing blood-brain barrier function in Alzheimer's and other diseases. Preserving distal axon function after transection.
Improving cognitive impairment by decreasing hippocampal hyeractivity.
New brain-machine interfaces for restoring neurologic function.
Reversing blood-brain barrier function in Alzheimer's and other diseases.
Preserving distal axon function after transection.
Memory loss and dementia states are devastating illnesses, the prevalence of which only threatens to increase as the world's population grows older. Most studies regarding Alzheimer's-type dementia and the accompanying prodromal cognitive impairments have illustrated the centrality of the hippocampus in the process of memory formation, with patients with Alzheimer's disease showing a marked reduction in hippocampal activity. On the other hand, it has recently been observed that in the prodromal states of amnestic mild cognitive impairment (aMCI), a condition where a person displays memory loss greater than would be expected for their age, there may actually be a paradoxical increase in hippocampal activity. However, the significance of the increased activity is controversial, with some theorizing that it may represent a compensatory mechanism for an otherwise failing hippocampus, and others positing that the excess activation may itself be a factor driving memory impairment.
Based on data from animal studies supporting the later hypothesis, the authors of the present study performed a clinical trial studying the cognitive effects of pharmacologically reducing this elevated hippocampal activity seen in patients with aMCI, to near-normal levels with the Food and Drug Administration (FDA)-approved agent, levetiracetam. Control and aMCI patients were studied in two treatment phases, with a washout period of 4 weeks in between. Controls received placebo medication for both phases, whereas aMCI patients received levetiracetam 125 mg BID during one phase and placebo during the other. The patients underwent functional magnetic resonance imaging with a behavioral paradigm of a 3-alternative forced choice task where subjects were presented with a series of images. A correct score was given if the subject correctly identified an image as “new” if they had never seen it before, “old” if they had seen the same image previously, or “similar” if the image resembled a previous item, with some detail changed. In their manuscript, the authors give as an example of such similar images 2 jack-o-lanterns with slightly different carvings. This task was chosen due to the fact the discernment of “similar” versus “old” images should rely heavily on the activity of the dentate gyrus of the hippocampus.
Using the control patients as a baseline, the authors presented the findings that pharmacologic treatment with levetiracetam diminished the elevated hippocampal activity to a level near baseline and reduced errors in which images were incorrectly judged as old and increased the number of correct responses that images were similar. Other cognitive and neuropsychological tests were not affected by the treatment and the effect of the treatment reversed within 4 weeks after discontinuation.
As a whole, this study demonstrates evidence that increased hippocampal activity in patients with mild cognitive impairment is not likely a beneficial compensatory mechanism. On the contrary, the authors demonstrate that regulation of this hyperactivity appeared to be cognitively beneficial to patients, and perhaps as importantly, easily achieved with a readily available medication.
In the quest to develop a neural prosthetic to help spinal cord-injured patients regain meaningful function, 2 significant incremental steps were presented in the May issue of the journal Nature. The first reports a significant advance in the development of neuroprostheses that rely on functional electrical stimulation (FES).[
In another study, Hochberg et al. present a different form of neuroprosthesis in using a neural interface system to control a robotic arm.[
Together, these 2 studies are cause for much hope for those suffering from spinal cord and paralyzing brain injuries to one day regain independent function.
Apolipoprotein E isoform is a major genetic risk factor for Alzheimer's disease and is associated with Down's syndrome dementia and poor neurologic outcome after traumatic brain injury and hemorrhage. In the present study, Bell et al. describe a possible mechanism to explain how APOE4 may increase susceptibility to brain injury and neuronal degeneration by damaging the blood-brain barrier (BBB).[
After axotomy, the part of the axon severed from the cell body degenerates distal to the injury in a process known as Wallerian degeneration. While such clear-cut axonal transections are rare in the clinical arena, Wallerian-like degeneration proceeds after traumatic brain and spinal cord injuries and is implicated in diseases, such as Parkinson's, glaucoma, and multiple sclerosis. Traditionally, it has been held that the process resulted in axons that were essentially starved of nutrients from the cell body. However, as Osterloh et al. have recently reported in Science, there is mounting evidence that Wallerian degeneration is actually an active process much more akin to apoptosis, or programmed cell death, that occurs throughout the body.[
Dietary alteration as a treatment for epilepsy has been used since the time of the ancient Greeks. Presently, the ketogenic diet has regained popularity for its use in reducing seizures mainly in children with medication refractory epilepsy. However, not much is known about the mechanism by which such metabolic alterations may lead to changes in seizure frequency or severity. This month in Neuron, Gimenez-Cassina et al. lend some insight into how this may occur.[
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