RESUMEN
BACKGROUND: Blocking the RhoA/ROCK II/MLC 2 (Ras homolog gene family member A/Rho kinase II/myosin light chain 2) signaling pathway can initiate neuroprotective mechanisms against neurological diseases such as stroke, cerebral ischemia, and subarachnoid hemorrhage. Nevertheless, it is not clear whether and how disrupting the RhoA/ROCK II/MLC 2 signaling pathway changes the pathogenic processes of the blood-brain barrier (BBB) after intracerebral hemorrhage (ICH). The present investigation included the injection of rat caudal vein blood into the basal ganglia area to replicate the pathophysiological conditions caused by ICH. METHODS: Scalp acupuncture (SA) therapy was performed on rats with ICH at the acupuncture point "Baihui"-penetrating "Qubin," and the ROCK selective inhibitor fasudil was used as a positive control to evaluate the inhibitory effect of acupuncture on the RhoA/ROCK II/MLC 2 signaling pathway. Post-assessments included neurological deficits, brain edema, Evans blue extravasation, Western blot, quantitative polymerase chain reaction, and transmission electron microscope imaging. RESULTS: We found that ROCK II acts as a promoter of the RhoA/ROCK II/MLC 2 signaling pathway, and its expression increased at 6 h after ICH, peaked at 3 days, and then decreased at 7 days after ICH, but was still higher than the pre-intervention level. According to some experimental results, although 3 days is the peak, 7 days is the best time point for acupuncture treatment. Starting from 6 h after ICH, the neurovascular structure and endothelial cell morphology around the hematoma began to change. Based on the changes in the promoter ROCK II, a 7-day time point was selected as the breakthrough point for treating ICH model rats in the main experiment. The results of this experiment showed that both SA at "Baihui"-penetrating "Qubin" and treatment with fasudil could improve the expression of endothelial-related proteins by inhibiting the RhoA/ROCK II/MLC 2 signaling pathway and reduce neurological dysfunction, brain edema, and BBB permeability in rats. CONCLUSION: This study found that these experimental data indicated that SA at "Baihui"-penetrating "Qubin" could preserve BBB integrity and neurological function recovery after ICH by inhibiting RhoA/ROCK II/MLC 2 signaling pathway activation and by regulating endothelial cell-related proteins.
Asunto(s)
Terapia por Acupuntura , Barrera Hematoencefálica , Hemorragia Cerebral , Modelos Animales de Enfermedad , Cadenas Ligeras de Miosina , Ratas Sprague-Dawley , Transducción de Señal , Quinasas Asociadas a rho , Proteína de Unión al GTP rhoA , Animales , Barrera Hematoencefálica/efectos de los fármacos , Quinasas Asociadas a rho/metabolismo , Hemorragia Cerebral/terapia , Transducción de Señal/efectos de los fármacos , Masculino , Cadenas Ligeras de Miosina/metabolismo , Proteína de Unión al GTP rhoA/metabolismo , Ratas , Puntos de Acupuntura , Miosinas Cardíacas/metabolismo , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/farmacología , Proteínas de Unión al GTP rhoRESUMEN
Acupuncture can intervene in and treat ischemic stroke (IS) through multiple targets and pathways. In recent years, experimental studies have shown that the mechanism of acupuncture in the treatment of IS mainly involves the promotion of nerve repair and regeneration, the regulation of the activity of neurotransmitters, the improvement of cerebral blood flow, the alleviation of brain edema, the reduction of oxidative stress, the inhibition of apoptosis and autophagy, and the suppression of inflammatory responses. This paper reviewed the available mechanisms of acupuncture in the treatment of IS to provide theoretical support for the clinical application of acupuncture against IS and references for further research.
Asunto(s)
Terapia por Acupuntura , Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Apoptosis , Isquemia Encefálica/terapia , Circulación Cerebrovascular , HumanosRESUMEN
Acupuncture therapy has been widely used in clinical treatment of consciousness, cognitive function, mental and motor disorders after intracerebral hemorrhage (ICH) in China, and has achieved good results. We, in the present paper, summarized development of studies on the underlying mechanism of acupuncture therapy for ICH in recent 20 years. Outcomes showed that acupuncture can relieve symptoms of ICH by 1) inhibiting inflammatory response, 2) alleviating brain edema, 3) inhibiting apoptosis, 4) activating autophagy, 5) inhibiting iron death, 6) alleviating oxidative stress, 7) promoting nerve regeneration, 8) improving brain circulation, 9) regulating neurotransmitter levels, and 10) promoting angiogenesis. In the future, we suggest that clinical trials for exploring the rule of dialectical acupoint selection in the treatment of ICH should be strengthened, and in-depth studies on the interrelation among the acupuncture targets are conducted to improve the theory of acupuncture effects.