Angiogenesis opens a way for Chinese medicine to treat stroke / 中国结合医学杂志

Based on the pathophysiology of the brain, advance in angiogenesis induced by stroke, and evidences of Chinese-medicine-mediated angiogenesis, the possibility to study the stroke-treating mechanism of Chinese medicine in angiogenesis was discussed. And regarding our previous work on angiogenesis modulated by qi-tonifying and stasis-eliminating therapy following intracerebral hemorrhage, we proposed some questions, which should be taken into account in the further work.

Electroacupuncture at Zusanli (ST36) accelerates intracerebral hemorrhage-induced angiogenesis in rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of electro-acupuncture on intracerebral hemorrhage (ICH)-induced angiogenesis and hypoxia-inducible factor-1α (HIF-1α) expression in rats.</p><p><b>METHODS</b>Adult male Sprague-Dawley rats were randomly divided into 4 groups of 24 rats each. ICH was induced in 3 groups by stereotactic injection of collagenase type VII into the right globus pallidus; of these, one group was not further treated, the second group underwent Zusanli (ST36)-acupuncture, and the third group underwent non-acupoint acupuncture. The fourth group underwent sham operations. Acupuncture was performed by stimulation with electrical needles at frequencies of 2-20 Hz for 30 min per day. Angiogenesis on days 3, 7 and 14 was assessed by double immunolabeling, and expression of HIF-1α was evaluated by immunohistochemistry, quantitative real time reverse transcription-polymerase chain reaction and Western blotting.</p><p><b>RESULTS</b>5-Bromo-2-deoxyuridine (BrdU)-labeled nuclei in cerebral endothelial cells (ECs) resided around the hematoma and the labeling peaked from 7 to 14 days (P<0.01). HIF-1α positive microvessels with a dilated outline were detected in perihematomal tissues after ICH, with the vessels extending into the clot from the surrounding area beginning on day 7. Following ICH, HIF-1α protein levels increased (P<0.05), but HIF-1α mRNA levels did not change. Electro-acupuncture at the Zusanli (ST36) acupoint increased BrdU-labeled nuclei in cerebral ECs (P<0.05) and up-regulated the expression of HIF-1α protein (P<0.05), but had little effect on the spatial distribution of HIF-1α or on HIF-1α mRNA levels.</p><p><b>CONCLUSIONS</b>Electro-acupuncture treatment at the Zusanli (ST36) acupoint may accelerate ICH-induced angiogenesis by up-regulating HIF-1α protein, and may enhance recovery following hemorrhagic cerebral injury.</p>

A strategy for detecting absorbed bioactive compounds for quality control in the water extract of rhubarb by ultra performance liquid chromatography with photodiode array detector / 中国结合医学杂志

<p><b>OBJECTIVE</b>To detect absorbed bioactive compounds of the water extract whose pharmacodynamic effect was craniocerebral protection for quality control assessment.</p><p><b>METHODS</b>Anthraquinones in water extract of rhubarb (WER), in cerebrospinal fluid (CSF) of patients with traumatic brain injury (TBI) and in ipsilateral cortex of TBI rats following oral WER were respectively explored by ultra performance liquid chromatography with photodiode array detector (UPLC-PDA) method developed in the present study. The effects of anthraquinones absorbed into injured cortex on superoxidase dismutase (SOD) activity in TBI rats were detected. The antioxidative anthraquinones absorbed into target organ were evaluated for quality control of WER.</p><p><b>RESULTS</b>Anthraquinones in WER were aloe-emodin, rhein, emodin, chrysophanol, and physcion. Only the last anthraquinone was found in CSF and in ipsilateral cortex under this chromatographic condition. Physcion increased SOD activity in TBI rats significantly.</p><p><b>CONCLUSIONS</b>Physcion was the main active compound of rhubarb against craniocerebral injury via antioxidant pathway. According to our strategy, the exploration of physcion suggested the possibility of a novel quality control of WER in treating TBI injury.</p>

Clinical observation on continuous electroacupuncture at Neiguan (PC 6) for arousing consciousness of comatose patients with severe craniocerebral trauma / 中国针灸

<p><b>OBJECTIVE</b>To observe the therapeutic effect of continuous electroacupuncture at Neiguan (PC 6) on the basis of routine treatment of western medicine for arousing consciousness of comatose patinents with severe craniocerebral trauma.</p><p><b>METHODS</b>Fifty-six cases of severe cranio cerebral trauma patients whose scores of Glasgow Coma Scale (GCS) lower than 8 were randomly divided into an observation group (29 cases) and a control group (27 cases). Both groups were treated with routine western medicine. The observation group were additionally treated with continuous electroacupuncture at Neiguan (PC 6) as the main point. Arousal rate and time after one month and three months of two groups were observed, arousal rate and the total therapeutic effect of recovery of the patients with different types after three months were compared between two groups.</p><p><b>RESULTS</b>The arousal time of the observation group was (18.57 +/- 7.14) days and the arousal rate was 72.4% (21/29) after one month, while (24.60 +/- 5.00) days and 37.0% (10/27) in control group, respectively. They were suprior in observation group to those in control group (P < 0.01, P < 0.05); the arousal time was (25.04 +/- 16.68) days in the observation group after three months of treatment, also shorter than (37.90 +/- 16.94) days in control group (P < 0.05). The arousal rate of patients with diffuse axonal injury was significantly higher than that of patients with non-diffuse axonal injury in the observation group and patients with the same type in control group after one month (P < 0.05). The cured-markedly effective rate of 72.4% (21/29) in observation group was significantly higher than that of 37.0% (10/27) in control group (P < 0.05).</p><p><b>CONCLUSION</b>The therapy of continunous electroacupuncture at Neiguan (PC 6) on the basis of routine western medicine has a better therapeutic effect for comatose patients with severe cranio cerebral trauma, especially for those with diffuse axonal injury.</p>

Effect of qi-tonifying and stasis-eliminating therapy on expression of vascular endothelial growth factor and its receptors Flt-1, Flk-1 in the brain of intracerebral hemorrhagic rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effects and mechanism of qi-tonifying and stasis-eliminating (QTSE) therapy on the expression of vascular endothelial growth factor (VEGF) and its receptors Flt-1 and Flk-1 in the brains of intracerebral hemorrhagic (model) rats.</p><p><b>METHODS</b>One hundred and eighty Sprague-Dawley rats were randomly divided into six groups: the normal group (n=5), the sham-operative (SO) group (n=35), the model group (n=35), the QTSE group (n=35), the QT group (n=35) and the SE group (n=35). All the rats except those in the normal group and SO group were established into an intracerebral hemorrhage(ICH) model by intracerebral injection of collagenase type VII and the latter three were orally administered with Buyang Huanwu Decoction (a classical recipe for QTSE) or with some of its components for qi-tonification and for stasis-elimination, respectively. To the other three groups, normal saline solutions were given instead. Behavioral tests were carried out in the animals randomly chosen from each group on days 1, 2, 4, 7, 14, 21 and 28 after modeling. The expressions of VEGF, Flk-1 and Flt-1 were determined by immunohistochemistry and the number of vascular segments with positive expression in the injured brain area of the rats was calculated.</p><p><b>RESULTS</b>From day 7 onwards, the asymmetric forelimb use rate in the QTSE group recovered more significantly than that in the other model groups. In the model group, the expressions of VEGF, Flk-1 and Flt-1 appeared on day 1 and reached a peak on day 21, then weakened gradually. In the QTSE group, as compared with the other model groups, a higher level of VEGF expression was shown from day 7 (P<0.01) and a higher level of Flt-1 expression was shown from the 7th day to the 21st day (P<0.01).</p><p><b>CONCLUSION</b>QTSE therapy can up-regulate the expressions of VEGF and its receptors (Flk-1 and Flt-1) and improve the recovery of kinetic function in the ICH rats, which may be correlated with its action in modulating vascular regeneration to promote the reconstruction of microvascular networks in the damaged areas.</p>

Activation of endogenous neural stem cells in experimental intracerebral hemorrhagic rat brains / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Many researchers suggest that adult mammalian central nervous system (CNS) is incapable of completing self-repair or regeneration. And there are accumulating lines of evidence which suggest that endogenous neural stem cells (NSCs) are activated in many pathological conditions, including stroke in the past decades, which might partly account for rehabilitation afterwards. In this study, we investigated whether there was endogenous neural stem cell activation in intracerebral hemorrhagic (ICH) rat brains.</p><p><b>METHODS</b>After ICH induction by stereotactical injection of collagenase type VII into globus pallidus, 5-Bromo-2 Deoxyuridine (BrdU) was administered intraperitoneally to label newborn cells. Immunohistochemical method was used to detect Nestin, a marker for neural stem cells, and BrdU.</p><p><b>RESULTS</b>Nestin-positive or BrdU-Labeled cells were predominantly located at 2 sites: basal ganglion around hemotoma, ependyma and nearby subventricular zone (SVZ). No positive cells for the 2 markers were found in the 2 sites of normal control group and sham group, as well as in non-leisioned parenchyma, both hippocampi and olfactory bulbs in the 4 groups. Nestin+ cells presented 4 types of morphology, and BrdU+ nucleus were polymorphologic. Positive cell counting around hemotoma showed that at day 2, Nestin+ cells were seen around hemotoma in model group, the number of which increased at day 4, day 7 (P <0.01), peaked at day 14 (P <0.05), and reduced significantly by day 28 (P <0.01).</p><p><b>CONCLUSION</b>Endogenous neural stem cells were activated in experimental intracerebral hemorrhagic rat brains.</p>