脳梗塞の治療において、電気パルスの正確なタイミングを制御することが期待される(Controlling the precise timing of electrical pulses may offer promise for treating mild traumatic brain injury)

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2024-06-18 バージニア工科大学(VirginiaTech)

An image of a brain cell
Virginia Tech scientists with the Fralin Biomedical Research Institute at VTC have published a study in the Journal of Neurotrama that shows that certain timing patterns of neurostimulation — impulses used to activate the brain’s own electrical signaling mechanisms — can play a role in rebalancing the strength of connections between nerve cells, particularly after brain injury. Image courtesy of Adobe Stock.

Virginia Techの研究者たちは、軽度外傷性脳損傷からの回復において、神経刺激のタイミングパターンがシナプス結合の強さを再調整できることを示しました。この研究は、Journal of Neurotraumaに発表され、自然なノイズのあるパターンのインパルスを使用することで、脳のシグナル伝達経路を再調整し、損傷後の神経結合を強化できる可能性を示唆しています。特定の周波数で不規則なパターンが、正常な脳では結合を弱める一方、損傷を受けた脳では結合を強化することが判明しました。この研究は、軽度外傷性脳損傷の治療法を最適化するための重要な洞察を提供し、他の脳障害の治療にも応用できる可能性があります。

<関連情報>

傷害を受けた脳のシナプス可塑性は刺激の時間パターンに依存する SYNAPTIC PLASTICITY IN THE INJURED BRAIN DEPENDS ON THE TEMPORAL PATTERN OF STIMULATION

Dr. Quentin S Fischer, Dr. Djanenkhodja Kalikulov, Dr. GONZALO VIANA DI PRISCO, Dr. Carrie A Williams, Dr. Philip R Baldwin, and Dr. Michael J Friedlander
Journal of Neurotrauma  Published:31 May 2024
DOI:https://doi.org/10.1089/neu.2024.0129

Abstract

Neurostimulation protocols are increasingly used as therapeutic interventions, including for brain injury. In addition to the direct activation of neurons, these stimulation protocols are also likely to have downstream effects on those neurons’ synaptic outputs. It is well known that alterations in the strength of synaptic connections (long-term potentiation, LTP; long-term depression, LTD) are sensitive to the frequency of stimulation used for induction, however little is known about the contribution of the temporal pattern of stimulation to the downstream synaptic plasticity that may be induced by neurostimulation in the injured brain. We explored interactions of the temporal pattern and frequency of neurostimulation in the normal cerebral cortex and after mild traumatic brain injury (mTBI), to inform therapies to strengthen or weaken neural circuits in injured brains, as well as to better understand the role of these factors in normal brain plasticity. Whole-cell (WC) patch-clamp recordings of evoked postsynaptic potentials (PSPs) in individual neurons, as well as field potential (FP) recordings, were made from layer 2/3 of visual cortex in response to stimulation of layer 4, in acute slices from control (naïve), sham operated, and mTBI rats. We compared synaptic plasticity induced by different stimulation protocols, each consisting of a specific frequency (1 Hz, 10 Hz, or 100 Hz), continuity (continuous or discontinuous), and temporal pattern (perfectly regular, slightly irregular, or highly irregular). At the individual neuron level, dramatic differences in plasticity outcome occurred when the highly irregular stimulation protocol was used at 1 Hz or 10 Hz, producing an overall LTD in controls and shams, but a robust overall LTP after mTBI. Consistent with the individual neuron results, the plasticity outcomes for simultaneous FP recordings were similar, indicative of our results generalizing to a larger scale synaptic network than can be sampled by individual WC recordings alone. In addition to the differences in plasticity outcome between control (naïve or sham) and injured brains, the dynamics of the changes in synaptic responses that developed during stimulation were predictive of the final plasticity outcome. Our results demonstrate that the temporal pattern of stimulation plays a role in the polarity and magnitude of synaptic plasticity induced in the cerebral cortex while highlighting differences between normal and injured brain responses. Moreover, these results may be useful for optimization of neurostimulation therapies to treat mTBI and other brain disorders, in addition to providing new insights into downstream plasticity signaling mechanisms in the normal brain.

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