Table 3.
The p38 signaling pathway in cerebral ischemic stroke.
| Study | Model | Intervention | Acupoints | Evaluation | Result |
|---|---|---|---|---|---|
| Bäcker et al., (2003) [13] | Healthy human | MA; manipulation as either high frequency (4–8 Hz) and low amplitude (Hf–La) or low frequency (1–2 Hz) and high amplitude (Lf–Ha). | Right LI4 | Cerebral blood flow velocity (CBFV) in both middle cerebral arteries, arterial blood pressure (BP), heart rate (HR). | (1) Lf–Ha stimulation was perceived as more intense and markedly increased the CBFV in the right hemisphere; (2) Hf–La stimulation slightly decreased BP and HR; (3) Lf–Ha stimulation induced an initial pressor response (increase of BP, decrease of HR) and a more marked long-term BP reduction. |
| Hsieh et al., (2006) [14] | SD rats | EA, 2-Hz, 15 min | Both ST36 | The levels of nitric oxide in the peripheral blood and amounts of calcitonin gene-related peptide (CGRP) in the cerebral cortex and thalamus. L-N (G)-nitro arginine methyl ester (L-NAME) was used to measure the changes in CBF. | Both 2- and 15-Hz EA increased CBF in rats with and without CI. |
| Cheng et al. (2014) [147] | SD rats | EA, 2-Hz, 25 min once daily for 2 consecutive days. | GV20, GV14 | Cerebral infarct area, caspase-3, BDNF, pRaf-1, MEK1/2, ERK1/2, p90RSK, and Bad. | EA significantly reduced the cerebral infarct area, caspase-3 protein expression levels, and apoptosis in the ischemic cortex. BDNF, phospho-Raf-1 (pRaf-1), phospho-MEK1/2 (pMEK1/2), phospho-ERK1/2 (pERK1/2), phospho-90 kDa ribosomal S6 kinase (pp90RSK), and phospho-Bad (pBad) were markedly upregulated, and neuronal nuclear antigen (NeuN) expression was restored. |
| Cheng et al. (2014) [161] | SD rats | EA, 2-Hz, 15 min once daily for 6 consecutive days. | GV20, GV14 | Cerebral infarct area, GFAP, S100B, NF-κB, p50, p38 MAPK, TNF-α, and iNOS. | EA significantly reduced the cerebral infarct area and downregulated astrocytic S100B expression and decreased p-p38 NF-kB. |
| Cheng et al. (2015) [203] | SD rats | EA, 5- or 25-Hz, 30 min once daily for 7 consecutive days. | GV20, GV16 | Cerebral infarct area, GFAP, Bax, Bcl-xL, Smac/DIABLO, p-p38, and CREB. | Both 5- and 25-Hz EA effectively downregulated reactive astrocytosis to exert neuroprotective effects against cerebral infarction, most likely by activating the p38 MAPK/CREB signaling pathway. |
| Xu et al. (2014) [208] | SD rats | EA, 2-Hz, 20 min once a day. | GV20, ST36 | Hsp70 and TNF-α peripheral serum. | Lowered peak levels of adrenocorticotrophic hormone and Hsp70. |
| Kuo et al. (2016) [15] | SD rats | Electrostimulation, 2-Hz, 20 min once daily for 7 consecutive days. | Both ears | Brain nicotinic acetylcholine receptors. | Two-hertz ES for ameliorated learning and memory impairment. |
GFAP: glial fibrillary acidic protein; iNOS: inducible nitric oxide synthase; MA: manual acupuncture; Smac/DIABLO: second mitochondrial-derived activator of caspase/direct inhibitor of apoptosis protein-binding protein with low isoelectric point.