Abstract
Subarachnoid hemorrhage (SAH) is a life-threatening condition that can also lead to permanent paralysis. However, the mechanisms that underlying neurobehavioral deficits after SAH have not been fully elucidated. As theta burst stimulation (TBS) can induce long-term potentiation (LTP) in the motor cortex, we tested its potential as a functional evaluation tool after experimentally induced SAH. Motor cortical inter-neuronal excitability was evaluated in anesthetized rats after 200 Hz-quadripulse TBS (QTS5), 200 Hz-quadripulse stimulation (QPS5), and 400 Hz-octapulse stimulation (OPS2.5). Furthermore, correlation between motor cortical LTP and N-methyl-D-aspartate-receptor activation was evaluated using MK-801, a NMDA-receptor antagonist. We evaluated inhibition-facilitation configurations [interstimulus interval: 3 ms; short-latency intracortical inhibition (SICI) and 11 ms; intracortical facilitation (ICF)] with paired electrical stimulation protocols and the effect of TBS paradigm on continuous recording of motor-evoked potentials (MEPs) for quantitative parameters. SAH and MK-801 completely blocked ICF, while SICI was preserved. QTS5, QPS5, and OPS2.5 facilitated continuous MEPs, persisting for 180 min. Both SAH and MK-801 completely blocked MEP facilitations after QPS5 and OPS2.5, while MEP facilitations after QTS5 were preserved. Significant correlations were found among neurological scores and 3 ms-SICI rates, 11 ms-ICF rates, and MEP facilitation rates after 200 Hz-QTS5, 7 days after SAH (R2 = 0.6236; r = −0.79, R2 = 0.6053; r = −0.77 and R2 = 0.9071; r = 0.95, p < 0.05, respectively). Although these findings need to be verified in humans, our study demonstrates that the neurophysiological parameters 3 ms-SICI, 11 ms-ICF, and 200 Hz-QTS5-MEPs may be useful surrogate quantitative biomarkers for assessing inter-neuronal function after SAH.
Highlights
Survivors of subarachnoid hemorrhage (SAH) are confronted with a variety of long-term problems, including focal neurological deficits, cognitive declines, and higher brain dysfunction, which can be difficult to evaluate (Hackett and Anderson, 2000; Kreiter et al, 2002; Jeon et al, 2010; Sherchan et al, 2011)
The study was composed of three different experimental sessions involving 50 animals: [A] continuous motor-evoked potentials (MEPs) recording after 200 Hz-quadripulse Theta burst stimulation (TBS), 200 Hz-QPS, and 400 Hz-OPS (QTS5, QPS5, and OPS2.5, respectively, n = 5, each condition); [B] the same procedure as in [A], but with NMDA-receptor antagonist MK-810 (1 mg/kg) administration to explore the correlation between MEP modification and NMDA activation (n = 5, each condition); [C] same procedure as in [A], but 7 days after SAH to explore the underlying functional consequences and pathophysiology (n = 5, each condition; Figure 1)
Whether there were any quantitative differences in cell number between the SAH and no-TBS control animals were not investigated
Summary
Survivors of subarachnoid hemorrhage (SAH) are confronted with a variety of long-term problems, including focal neurological deficits, cognitive declines, and higher brain dysfunction, which can be difficult to evaluate (Hackett and Anderson, 2000; Kreiter et al, 2002; Jeon et al, 2010; Sherchan et al, 2011). TBS stimulation has subsequently been translated to humans using non-invasive transcranial magnetic stimulation (TMS) of the motor cortex (three pulses at a frequency of 50 Hz-burst, repeated at 5 Hz, total, 600 pulses; Huang et al, 2005) It has been used either in intermittent and facilitatory or continuous and inhibitory TBS (iTBS and cTBS, respectively) paradigms for motor-evoked potentials (MEPs) with repetitive TMS (rTMS; Huang et al, 2005). TBS has widespread applications as a non-invasive methodology to evaluate and modify neural-networks within the human brain (Huang et al, 2005; Jung et al, 2016) To replicate these human findings, we explored inter-neuronal function in the motor cortex of a rat SAH model after TBS by comparing two standard LTP protocols. We tested the effects of an N-methyl-D-aspartate (NMDA)receptor antagonist (MK-801) on MEPs after TBS
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