Research ReportFunctional improvement and neuroplastic effects of anodal transcranial direct current stimulation (tDCS) delivered 1 day vs. 1 week after cerebral ischemia in rats
Highlights
► Anodal tDCS had benefits in acute cerebral ischemic rats. ► tDCS at 1 week (LT) was slightly more effective than 1 day after ischemia (ET). ► MAP-2 was increased around the peri-lesional area in ET group. ► GAP-43 was increased in the intact cortex of LT group. ► MRI and 1H MRS showed no differences among groups in ischemic volume and metabolites.
Introduction
Transcranial direct current stimulation (tDCS) is an emerging technique that has currently been applied in cerebral ischemic patients with motor dysfunction, impaired working memory, or aphasia (Baker et al., 2010, Boggio et al., 2007, Fregni et al., 2005, Hummel et al., 2005, Jo et al., 2009). It is a painless stimulation method that delivers subthreshold electrical currents to the brain and manipulates the resting membrane potential of cortical neurons by modulating sodium and calcium channels (Nitsche and Paulus, 2000, Poreisz et al., 2007). However, few clinical trials have been undertaken to evaluate the efficacy of tDCS in providing functional improvement after cerebral ischemia, and have enrolled only chronic stroke patients (Boggio et al., 2007, Fregni et al., 2005, Hummel et al., 2005). As there have been no animal experiments of tDCS in acute cerebral ischemia, DC stimulation is difficult to apply in acute stroke patients without any evidence of its safety.
After a stroke, the brain has the capability to reorganize the damaged tissue by means of dendritic branching, synaptic formation and neuronal sprouting, a process known as ‘neural plasticity’ (Gonzalez and Kolb, 2003, Schallert and Jones, 1993, Stroemer et al., 1995). As these changes are known to be time-dependent, the injured brain is highly plastic during the early stage after a stroke. A recent interesting report showed that neuronal growth-promoting genes such as GAP-43 (growth-associated protein 43) are expressed during the first week after ischemic injury (Carmichael et al., 2005). It also gradually loses its ability to reorganize over time (Nudo et al., 1996, Qu et al., 1998) although functional plasticity could be achieved at any time after stroke (Schaechter, 2004, Schaechter et al., 2006, Ward, 2005). However, peri-lesional neurons in the brain might be more vulnerable to excitation during this highly plastic period. In this context, several previous animal studies have shown that exercise training initiated very early after focal brain ischemia increased cortical infarct volume (Humm et al., 1999, Risedal et al., 1999).
Because no previous trials have been undertaken to determine whether tDCS has a therapeutic benefit in the early stage of cerebral ischemia, there has been no consensus on the optimal time window of tDCS. The purpose of this study is to evaluate the effect of tDCS on functional improvements and neuroplastic changes in a rat model of early stage cerebral ischemia, and determine the optimal time window to apply tDCS to maximize functional gains.
Section snippets
Behavioral and cognitive tests
Results of beam balance, motor behavioral index, rotarod, and Barnes maze are presented in Table 1. In the beam balance test, there was a significant interaction of group × time (F10, 135 = 6.187, p < 0.001, repeated measures ANOVA). The LT group showed significant improvement in beam balance test compared with ET and sham group at 2, 3, and 4 weeks after ischemic injury (p < 0.001, p < 0.001, p < 0.001, respectively; one way ANOVA with Scheffe's post-hoc test and Bonferroni correction; Table 1). A
Discussion
Previous studies using tDCS have been limited to chronic patients whose mean time after stroke was over 1 year (Boggio et al., 2007, Hummel et al., 2005). However, there have been no trials applying tDCS in the early stage of stroke. The present study, which represents the first attempt to elucidate the effects of tDCS on the early stage of cerebral ischemia, showed that both early (ET group) and late (LT group) treatments exerted beneficial effects on cognition, behavioral function, and neural
Animals
Thirty 6-week-old male Sprague–Dawley rats (220–280 g) were used for the investigation. Throughout the experiment, animals were housed in laboratory cage under controlled temperature conditions (22.0 °C–24.0 °C) and maintained under a 12/12 h light/dark cycle with free access to food and water. All protocols used in this study were approved by Institutional Animal Care and Use Committee of Asan Institute for Life Science (IACUC number: 2008-01-063).
Cerebral ischemic model
The cerebral ischemic rat model was made by Longa
Acknowledgments
This work was supported by a Korean Stroke Society young investigator's award (KSS-2008-002) and by a grant from Seoul Medical Center Research Institute (07-C09). The authors would like to thank Ms. Ho Sun Lee at the Asan Institute of Life Science.
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2021, Brain StimulationCitation Excerpt :In the current study, hippocampus and cerebral cortex were selected to measure the plasticity because the two brain areas are extremely vulnerable to global cerebral ischemia and reperfusion after CA in both experimental animals and humans [41,42,44,45]. As expected, repeated anodal tDCS significantly increased the levels of MAP-2, GAP-43, PSD-95 and SYN in cortex and hippocampus at the early stage of post resuscitation, and our data also agree with previous ischemia/reperfusion animal study that has suggested a pivotal role of anodal tDCS in improving behavioral and cognitive functions by modulating synaptic plasticity with reinforced MAP-2 expression and enhanced GAP-43 level [12]. The cortex may directly benefit from tDCS because this brain region is under the electrode and the hippocampus could be indirectly activated through the functional connectivity [13], but these need additional investigation in the future.