[Effect of moxibustion on Nogo/neurotrophin receptor signaling pathway in rats with cerebral ischemia/reperfusion injury].

OBJECTIVE: To observe the effect of moxibustion treatment on the expression of Nogo-A, Nogo receptor (NgR), neurotrophin receptor p75 (p75NTR) and leucine rich repeat and Ig domain containing 1 (Lingo-1) in brain tissue of rats with cerebral ischemia/reperfusion injury (CI/RI), so as to analyze its mechanism underlying improvement of CI/RI. METHODS: Male SD rats were randomly divided into sham operation group (16 rats), model group (17 rats), NEP1-40 (extracellular peptide residues 1-40, a blocker targeting NgR) group (model+blocker, 17 rats) and moxibustion group (model+moxibustion, 17 rats). The CI/RI model was established by occlusion of the left middle cerebral artery (MCAO). Moxibustion was applied to "Baihui"(GV20), right "Quchi"(LI11) and "Zusanli"(ST36) for 20 min, once a day for 14 days, with 2 days' rest after the top 7 days' intervention. For rats of the NEP1-40 group, 30 µL PBS containing 18 µg NEP 1-40 was injected into the epidural inferior vena (L5-S1) via a polyvinyl chloride conduit. The neurological deficit state in each group was evaluated by Longa's 5-point scale and Feeney's 7-point scale of beam walking test (BWT). The cerebral infarct volume was assessed by 2,3,5-triphenyltetrazole chloride staining. The brain tissue between the central anterior and posterior sulcus was taken for observing the expression of NgR and Lingo-1 by fluorescence double-label method, and for determining the expression levels of Nogo-A, NgR, p75NTR and Lingo-1 mRNAs and proteins by real-time quantitative PCR and Western blot, respectively. RESULTS: After modeling, the Longa's score, infarct volu-me percent, expression levels of Nogo-A, NgR, Lingo-1 and p75NTR mRNAs and proteins were significantly increased (P<0.01) and BWT score was obviously decreased (P<0.01) in the model group relevant to the sham operation group. In comparison with the model group, the increase of Longa's score, infarct volume percentage, expression levels of Nogo-A, NgR, Lingo-1 and p75NTR mRNAs and proteins and decrease of BWT score in NEP1-40 and moxibustion groups were reversed (P<0.01) except Nogo-A protein in the NEP1-40 group. The effect of moxibustion was significantly superior to that of blocker NEP1-40 in redu-cing the infarct volume percentage, and down-regulating the expression of Nogo-A mRNA and protein, p75NTR mRNA and protein, NgR and Lingo-1 proteins (P<0.01, P<0.05). CONCLUSION: Moxibustion, similar to blocker NEP1-40 of NgR, can improve neurological dysfunction in CI/RI rats, which may be related to its functions in reducing cerebral infarction and down-regulating the activity of Nogo/neurotrophin receptor signaling pathway.

Coenzyme Q10 supplementation in acute ischemic stroke: Is it beneficial in short-term administration?

Backgrounds and aims: Clinical studies demonstrated that the efficacy of Coenzyme Q10 (CoQ10) as an adjuvant therapeutic agent in several neurological diseases such as Parkinson disease (PD), Huntington disease (HD), and migraine. The purpose of this study is to investigate oxidative stress effects, antioxidant enzymes activity, neuroinflammatory markers levels, and neurological outcome in acute ischemic stroke (AIS) patients following administration of CoQ10 (300 mg/day). Methods: Patients with AIS (n = 60) were randomly assigned to a placebo group (wheat starch, n = 30) or CoQ10-supplemented group (300 mg/day, n = 30). The intervention was administered for 4 weeks. Serum CoQ10 concentration, malondialdehyde (MDA), superoxide dismutase (SOD) activity, glial fibrillary acidic protein (GFAP) levels as primary outcomes and National Institute of Health Stroke Scale (NIHSS), Modified Ranking Scale (MRS), and Mini-Mental State Examination (MMSE) as secondary outcome were measured at the both beginning and end of the study. Results: Forty-four subjects with AIS completed the intervention study. A significant increase in CoQ10 level was observed in the supplement-treated group compared with placebo group (mean difference = 26.05 ± 26.63 ng/ml, 14.12 ± 14.69 ng/ml, respectively; P = 0.01), moreover CoQ10 supplementation improved NIHSS and MMSE scores significantly (P = 0.05, P = 0.03 respectively). but there were no statistically significant differences in MRS score, MDA, SOD, and GFAP levels between the two groups. Conclusions: CoQ10 probably due to low dose and short duration of supplementation, no favorable effects on MDA level, SOD activity and GFAP level.

Parthenolide ameliorates intracerebral hemorrhage-induced brain injury in rats.

Neuroinflammation and oxidative stress are key contributors to intracranial hemorrhage (ICH)-induced brain injury. Parthenolide (PN) is a sesquiterpene lactone that has been observed to have antioxidative, anti-inflammatory, and neuroprotective potentials. However, the role of PN in ICH remains unclear. Therefore, we investigated the neuroprotective effects and underlying mechanisms of PN on an experimental model of ICH in rats. Our results showed that PN treatment improved neurological deficit and brain edema in ICH rats. The ipsilateral hemispheres of the brain were separated and homogenized. The concentrations of TNF-α, interleukin (IL)-6, and IL-17 in the homogenates were detected by enzyme-linked immunosorbent assay. We found that PN inhibited the production of proinflammatory cytokines in an ICH rat model. The ROS and glutathione (GSH) levels, as well as the activity of superoxide dismutase (SOD) in the homogenates were measured. ICH caused an increase in ROS level, and the decreases in GSH level and SOD activity were mitigated by PN treatment. Furthermore, PN significantly suppressed the expressions of active caspase-3 and Bax in ipsilateral hemispheres of the brain at Day 3 after ICH, as well as increased the surviving neurons. Finally, the ICH-induced activation of TLR4/NF-κB pathway was suppressed by PN treatment. These findings suggested that PN could be beneficial in the therapeutic strategy for ICH treatment.

Neuroprotective Activity of D-HES in Transient Global Cerebral Ischemia in Rats.

We studied the effect of O-((((4-hydroxy-3,5-di(1,7,7-trimethylbicyclo[2.2.1]hept-exo-2-yl) benzyl)oxy)ethyl)-O-(2-hydroxyethyl)-(1→4)-α-D-glucan (D-HES, 80 mg/kg, intravenously) and reference preparation ethylmethylhydroxypyridine succinate (EMHP-S, 50 mg/kg, intravenously) on rat survival and neurological deficit in 24 h after transient global cerebral ischemia in Wistar rats. Intravenous administration of D-HES and EMHP-S significantly increased the number of survivors by 68 and 78%, respectively, in comparison with the control group. In groups treated with D-HES and EMHP-S, the number of animals with severe neurological deficit was significantly lower and the number of animals moderate or mild neurological deficit was significantly higher than in the control group.

Korean Red Ginseng Pretreatment Protects Against Long-Term Sensorimotor Deficits After Ischemic Stroke Likely Through Nrf2.

Endogenous neuroprotective mechanisms by which the brain protects itself against noxious stimuli and recovers from ischemic damage are key targets of stroke research, ultimately facilitating functional recovery. Transcriptional factor Nrf2, enriched in astrocytes, is a master regulator of endogenous defense systems against oxidative stress and inflammation. Korean Red Ginseng (Ginseng), one most widely used herbal medicine, has exhibited promising potentials in neuroprotection. Our study aimed to determine whether the standardized Ginseng extract pretreatment could attenuate acute sensorimotor deficits and improve long-term functional recovery after ischemic stroke though Nrf2 pathway and whether reactive astrogliosis is associated with such effect. Adult Nrf2-/- and matched wildtype control (WT) mice were pretreated with Ginseng orally for 7 days prior to permanent distal middle cerebral artery occlusion (pdMCAO). Using an optimized method that can accurately assess either severe or mild pdMCAO-induced sensorimotor deficits, neurobehavioral tests were performed over 28 days. The progression of lesion volume and the evolution of astrocytic and microglial activation were determined in the acute stage of ischemic stroke after pdMCAO (0-3 days). Nrf2-downstream target antioxidant genes expression levels was assessed by Western blot. We found that Ginseng pretreatment ameliorated acute sensorimotor deficits and promoted long-term functional recovery, prevented the acute enlargement of lesion volume (36.37 ± 7.45% on day 3), attenuated reactive astroglial progression but not microglia activation, and enhanced the induction of Nrf2-downstream target proteins after ischemic insult in WT mice, an effect which was lost in Nrf2 knockouts. The spatiotemporal pattern of reactive astrogliosis evaluation correlated well with acute ischemic damage progression in an Nrf2-dependent fashion during the acute phase of ischemia. In contrast, Nrf2 deficiency mice exhibited exacerbated ischemic condition compared to WT controls. Together, Ginseng pretreatment protects against acute sensorimotor deficits and promotes its long-term recovery after pdMCAO, at least partly, through Nrf2 activation, highlighting the potential efficacy of oral consumption of Ginseng for stroke preventative intervention in patients who are at great risk of recurrent stroke or transient ischemic attack. The attenuated reactive astrogliosis contributes to the Nrf2 pathway related neuroprotection against acute ischemic outcome and substantially long-term sensorimotor deficits in the context of ischemic stroke under pdMCAO.

Scalp acupuncture attenuates neurological deficits in a rat model of hemorrhagic stroke.

BACKGROUND: Hemorrhagic stroke accounts for approximately 15% of all stroke cases, and is associated with high morbidity and mortality. Limited human studies suggested that scalp acupuncture could facilitate functional recovery after cerebral hemorrhage. In the current study, we used an animal model of cerebral hemorrhage to examine the potential effects of scalp acupuncture. METHODS: Adult male Sprague-Dawley rats received autologous blood (50µL) into the right caudate nucleus on the right side under pentobarbital anesthesia, and then received scalp acupuncture (DU20 through GB7 on the lesion side) or sham acupuncture (1cm to the right side of the acupoints) (n=10 per group). A group of rats receiving autologous blood into the caudate nucleus but no other intervention, as well as a group of rats receiving anesthesia but no blood injection to the brain (n=10 per group) were included as additional controls. Composite neuroscore, corner turn test, forelimb placing test, wire hang task and beam walking were used to evaluate the behavior of rats. Hematoxylin and Eosin (HE) staining was used to observe the histopathological changes. Western blot was used to detect the content of tumor necrosis factor alpha (TNF-α) and nuclear factor-KappaB (NFκB) protein expression. RESULTS: Scalp acupuncture attenuated neurological deficits (p<0.01 or <0.05 vs. sham acupuncture using a variety of behavioral tests) at 1-7days after the treatment. The brain content of TNF-α and NFκB was decreased (p<0.01 for both). CONCLUSIONS: Scalp acupuncture could improve neurological deficits in a rat model of hemorrhagic stroke.

Clinical course of untreated thalamic cavernous malformations: hemorrhage risk and neurological outcomes.

OBJECTIVE The natural history of cerebral cavernous malformations (CMs) has been widely studied, but the clinical course of untreated thalamic CMs is largely unknown. Hemorrhage of these lesions can be devastating. The authors undertook this study to obtain a prospective hemorrhage rate and provide a better understanding of the prognosis of untreated thalamic CMs. METHODS This longitudinal cohort study included patients with thalamic CMs who were diagnosed between 2000 and 2015. Clinical data were recorded, radiological studies were extensively reviewed, and follow-up evaluations were performed. RESULTS A total of 121 patients were included in the study (56.2% female), with a mean follow-up duration of 3.6 years. The overall annual hemorrhage rate (subsequent to the initial presentation) was calculated to be 9.7% based on the occurrence of 42 hemorrhages over 433.1 patient-years. This rate was highest in patients (n = 87) who initially presented with hemorrhage and focal neurological deficits (FNDs) (14.1%) (χ2 = 15.358, p < 0.001), followed by patients (n = 19) with hemorrhage but without FND (4.5%) and patients (n = 15) without hemorrhage regardless of symptoms (1.2%). The initial patient presentations of hemorrhage with FND (hazard ratio [HR] 2.767, 95% CI 1.336-5.731, p = 0.006) and associated developmental venous anomaly (DVA) (HR 2.510, 95% CI 1.275-4.942, p = 0.008) were identified as independent hemorrhage risk factors. The annual hemorrhage rate was significantly higher in patients with hemorrhagic pres entation at diagnosis (11.7%, p = 0.004) or DVA (15.7%, p = 0.002). Compared with the modified Rankin Scale (mRS) score at diagnosis (mean 2.2), the final mRS score (mean 2.0) was improved in 37 patients (30.6%), stable in 59 patients (48.8%), and worse in 25 patients (20.7%). Lesion size (odds ratio [OR] per 0.1 cm increase 3.410, 95% CI 1.272-9.146, p = 0.015) and mRS score at diagnosis (OR per 1 point increase 3.548, 95% CI 1.815-6.937, p < 0.001) were independent adverse risk factors for poor neurological outcome (mRS score ≥ 2). Patients experiencing hemorrhage after the initial ictus (OR per 1 ictus increase 6.923, 95% CI 3.023-15.855, p < 0.001) had a greater chance of worsened neurological status. CONCLUSIONS This study verified the adverse predictors for hemorrhage and functional outcomes of thalamic CMs and demonstrated an overall annual symptomatic hemorrhage rate of 9.7% after the initial presentation. These findings and the mode of initial presentation are useful for clinicians and patients when selecting an appropriate treatment, although the tertiary referral bias of the series should be taken into account.

Sameerpannag Ras Mixture (SRM) improved neurobehavioral deficits following acute ischemic stroke by attenuating neuroinflammatory response.

ETHNOPHARMACOLOGICAL RELEVANCE: Cerebral ischemic stroke is one of the leading causes of death and long-term disability worldwide. Unfortunately, due to the failure of most of drugs in clinical trials recently, attentions have moved towards the traditional system of medicines including Ayurveda. In Ayurveda, Sameerpannag Ras (SR) is a mineral and metallic origin based formulation which has been used for the treatment of arthritis and chronic systematic inflammatory disorder. The current study was designed to investigate the neuroprotective effects of Sameerpannag Ras Mixture (SRM), on the neurobehavioral dysfunction and associated neuroinflammation, induced by transient Internal Carotid Artery Occlusion (ICAO) in mice model. MATERIALS AND METHODS: In the present study, mice were treated with Sameerpannag Ras Mixture (SRM) at the dose of 40mg/kg body weight by oral gavages for 3 and 7days respectively, twice a day, after the induction of ICAO for 90min followed by reperfusion. The efficacy of SRM was examined by scoring neurological behavioral deficit using the standard neurological deficit score (NDS), grip strength and rotarod performance tests at different time intervals of post-ICAO. RESULTS: Post-ischemic treatment with Sameerpannag Ras Mixture (SRM) at 40mg/kg significantly reduced Neurological Deficit Score and improved the motor coordination at different time intervals post-ICAO. The analysis of RT-qPCR data showed that transient cerebral ischemia could induce the inflammatory response genes in the affected striatal region of ICAO group, as compared to sham group, on day3 and day7 post-ICAO. Interestingly, SRM treatment showed marked improvement in the ischemia-induced neurobehavioral deficits by attenuating ischemia-induced neuroinflammatory response at both gene and protein level. CONCLUSION: The present study suggests that Sameerpannag Ras Mixture (SRM) treatment ameliorates behavioral outcomes after mild ischemia through the suppression of a number of inflammatory response genes involved in neuronal damage. This is the first report of the molecular mechanism underlying the significant neuroprotective action of the Ayurvedic drug, Sameerpannag Ras Mixture (SRM), using a mild stroke in mice model.

Hibiscus sabdariffa increases hydroxocobalamin oral bioavailability and clinical efficacy in vitamin B12 deficiency with neurological symptoms.

The aim of the study was to evaluate the bioavailability and clinical benefits of oral new formulation (HB12 ) of hydroxocobalamin (Hdrx) with Hibiscus sabdariffa (HS). First, in an observational study, a cohort of 30 vitamin B12 -deficient patients (vit B12 < 200 pg/mL) with neurological symptoms received oral fixed dose of Hdrx containing 15 mg Hdrx daily for 10 days followed by 15 mg monthly. Clinical benefits were evaluated on haematological and biochemical parameters, and neurological improvement at days 10 and 90 compared to day 0. To understand the mechanism, intestinal mucosa from mice were mounted in vitro in Ussing chambers to measure Hdrx Fluxes. In the clinical study, serum vitamin B12 level increased from 55.1 ± 36.9 to 1330 ± 335.5 pg/mL at day 10 and 431.0 ± 24.27 pg/mL at day 90, without overt adverse effects. In mice ileum, (i) intestinal bioavailability of Hdrx increased in dose-dependent manner with HB12 . The apparent permeability of Hdrx was Papp = 34.9 ± 4.6 × 10-6 cm/s in the presence of 3 mg/mL (HB12 B) compared to the control Papp = 6.2 ± 0.7 × 10-6 cm/s. (ii) Total transepithelial electrical conductance (Gt ) increased in dose-dependent manner with HB12 , Gt = 161.5 ± 10.8 mS/cm² with HB12 B (Hdrx 1 mg + HS 3 mg) compared to the control Hdrx, Gt = 28.7 ± 4.0 mS/cm². In conclusion, the clinical study suggests that injections are not required when Hdrx is given orally. Intestinal bioavailability of Hdrx increased in vitro when it was used concomitantly with HS.

Immediate effects of scalp acupuncture with twirling reinforcing manipulation on hemiplegia following acute ischemic stroke: a hidden association study.

Data mining has the potential to provide information for improving clinical acupuncture strategies by uncovering hidden rules between acupuncture manipulation and therapeutic effects in a data set. In this study, we performed acupuncture on 30 patients with hemiplegia due to acute ischemic stroke. All participants were pre-screened to ensure that they exhibited immediate responses to acupuncture. We used a twirling reinforcing acupuncture manipulation at the specific lines between the bilateral Baihui (GV20) and Taiyang (EX-HN5). We collected neurologic deficit score, simplified Fugl-Meyer assessment score, muscle strength of the proximal and distal hemiplegic limbs, ratio of the maximal H-reflex to the maximal M-wave (Hmax/Mmax), muscle tension at baseline and immediately after treatment, and the syndromes of traditional Chinese medicine at baseline. We then conducted data mining using an association algorithm and an artificial neural network backpropagation algorithm. We found that the twirling reinforcing manipulation had no obvious therapeutic difference in traditional Chinese medicine syndromes of "Deficiency and Excess". The change in the muscle strength of the upper distal and lower proximal limbs was one of the main factors affecting the immediate change in Fugl-Meyer scores. Additionally, we found a positive correlation between the muscle tension change of the upper limb and Hmax/Mmax immediate change, and both positive and negative correlations existed between the muscle tension change of the lower limb and immediate Hmax/Mmax change. Additionally, when the difference value of muscle tension for the upper and lower limbs was > 0 or < 0, the difference value of Hmax/Mmax was correspondingly positive or negative, indicating the scalp acupuncture has a bidirectional effect on muscle tension in hemiplegic limbs. Therefore, acupuncture with twirling reinforcing manipulation has distinct effects on acute ischemic stroke patients with different symptoms or stages of disease. Improved muscle tension in the upper and lower limbs, reflected by the variation in the Hmax/Mmax ratio, is crucial for recovery of motor function from hemiplegia.

Impacts of eye acupuncture on neurological deficit and Barthel index in patients of infarction hemiplegia / 中国针灸

<p><b>OBJECTIVE</b>To observe the impacts of eye acupuncture on neurological deficit and Barthel index in the patients of infarction hemiplegia and explore its function mechanism.</p><p><b>METHODS</b>Ninety-six patients of infarction hemiplegia were randomized into an observation group and a control group, 48 cases in each one. In the control group, the routine western medicines such as thrombolysis and antiplatelet aggregation were used. In the observation group, on the basis of the treatment as the control group, eye acupuncture was added atandareas bilaterally, once a day, 5 times a week. Separately, before treatment and after 2 weeks' treatment the score changes of the modified Edinburgh Scandinavia stroke scale (MESSS) and the activity of daily life scale (ADL, Barthel index, BI) were observed and the efficacy was compared between the two groups. The plasma endothelin was determined and compared before and after treatment in the two groups.</p><p><b>RESULTS</b>After treatment, the effective rate was 93.8% (45/48) in the observation group and was 79.2% (38/48) in the control group. The effective rate in the observation group was higher apparently than that in the control group (<0.05). The scores of neurological deficit were (13.29±1.45) and (18.24±1.33) in the observation group and control group respectively after treatment, which all lower apparently than (28.44±1.45) and (28.14±1.89) before treatment (both<0.05). Additionally, the difference was significant between the two groups after treatment (<0.05). The scores of Barthel index were (82.33±1.56) and (63.34±2.14) in the observation group and control group respectively, which all higher apparently than (38.53±1.54) and (38.14±2.56) before treatment (both<0.05), and the difference was significant between the two groups after treatment (<0.05). The levels of plasma endothelin were (54.55±11.48)ng/L and (62.44±9.88)ng/L in the observation group and the control group after treatment respectively, which were all lower apparently than (78.24±9.25)ng/L and (78.14±10.78)ng/L before treatment (both<0.05). Additionally, the difference was significant between the two groups after treatment (<0.05).</p><p><b>CONCLUSIONS</b>Eye acupuncture effectively improves the neurological deficit and Brathel index in the patients of infarction hemiplegia and comprehensively improves the efficacy. The effect mechanism is possibly relevant with reducing plasma endothelin.</p>

[Impacts of eye acupuncture on neurological deficit and Barthel index in patients of infarction hemiplegia].

OBJECTIVE: To observe the impacts of eye acupuncture on neurological deficit and Barthel index in the patients of infarction hemiplegia and explore its function mechanism. METHODS: Ninety-six patients of infarction hemiplegia were randomized into an observation group and a control group, 48 cases in each one. In the control group, the routine western medicines such as thrombolysis and antiplatelet aggregation were used. In the observation group, on the basis of the treatment as the control group, eye acupuncture was added at Shangjiao and Xiajiao areas bilaterally, once a day, 5 times a week. Separately, before treatment and after 2 weeks' treatment the score changes of the modified Edinburgh Scandinavia stroke scale (MESSS) and the activity of daily life scale (ADL, Barthel index, BI) were observed and the efficacy was compared between the two groups. The plasma endothelin was determined and compared before and after treatment in the two groups. RESULTS: After treatment, the effective rate was 93.8% (45/48) in the observation group and was 79.2% (38/48) in the control group. The effective rate in the observation group was higher apparently than that in the control group (P<0.05). The scores of neurological deficit were (13.29±1.45) and (18.24±1.33) in the observation group and control group respectively after treatment, which all lower apparently than (28.44±1.45) and (28.14±1.89) before treatment (both P<0.05). Additionally, the difference was significant between the two groups after treatment (P<0.05). The scores of Barthel index were (82.33±1.56) and (63.34±2.14) in the observation group and control group respectively, which all higher apparently than (38.53±1.54) and (38.14±2.56) before treatment (both P<0.05), and the difference was significant between the two groups after treatment (P<0.05). The levels of plasma endothelin were (54.55±11.48)ng/L and (62.44±9.88)ng/L in the observation group and the control group after treatment respectively, which were all lower apparently than (78.24±9.25)ng/L and (78.14±10.78)ng/L before treatment (both P<0.05). Additionally, the difference was significant between the two groups after treatment (P<0.05). CONCLUSIONS: Eye acupuncture effectively improves the neurological deficit and Brathel index in the patients of infarction hemiplegia and comprehensively improves the efficacy. The effect mechanism is possibly relevant with reducing plasma endothelin.

Molsidomine for the prevention of vasospasm-related delayed ischemic neurological deficits and delayed brain infarction and the improvement of clinical outcome after subarachnoid hemorrhage: a single-center clinical observational study.

OBJECT Delayed ischemic neurological deficits (DINDs) and cerebral vasospasm (CVS) are responsible fora poor outcome in patients with aneurysmal subarachnoid hemorrhage (SAH), most likely because of a decreased availability of nitric oxide (NO) in the cerebral microcirculation. In this study, the authors examined the effects of treatment with the NO donor molsidomine with regard to decreasing the incidence of spasm-related delayed brain infarctions and improving clinical outcome in patients with SAH. METHODS Seventy-four patients with spontaneous aneurysmal SAH were included in this post hoc analysis. Twenty-nine patients with SAH and proven CVS received molsidomine in addition to oral or intravenous nimodipine. Control groups consisted of 25 SAH patients with proven vasospasm and 20 SAH patients without. These patients received nimodipine therapy alone. Cranial computed tomography (CCT) before and after treatment was analyzed for CVS-related infarcts. A modified National Institutes of Health Stroke Scale (mNIHSS) and the modified Rankin Scale (mRS) were used to assess outcomes at a 3-month clinical follow-up. RESULTS Four of the 29 (13.8%) patients receiving molsidomine plus nimodipine and 22 of the 45 (48%) patients receiving nimodipine therapy alone developed vasospasm-associated brain infarcts (p < 0.01). Follow-up revealed a median mNIHSS score of 3.0 and a median mRS score of 2.5 in the molsidomine group compared with scores of 11.5 and 5.0, respectively, in the nimodipine group with CVS (p < 0.001). One patient in the molsidomine treatment group died, and 12 patients in the standard care group died (p < 0.01). CONCLUSIONS In this post hoc analysis, patients with CVS who were treated with intravenous molsidomine had a significant improvement in clinical outcome and less cerebral infarction. Molsidomine offers a promising therapeutic option in patients with severe SAH and CVS and should be assessed in a prospective study.

Dural arteriovenous fistula-induced thalamic dementia: report of 4 cases.

Nonhemorrhagic neurological deficits are underrecognized symptoms of intracranial dural arteriovenous fistulas (dAVFs) having cortical venous drainage. These symptoms are the consequence of cortical venous hypertension and portend a clinical course with increased risk of neurological morbidity and mortality. One rarely documented and easily misinterpreted type of nonhemorrhagic neurological deficit is progressive dementia, which can result from venous hypertension in the cortex or in bilateral thalami. The latter, which is due to dAVF drainage into the deep venous system, is the less common of these 2 dementia syndromes. Herein, the authors report 4 cases of dAVF with venous drainage into the vein of Galen causing bithalamic edema and rapidly progressive dementia. Two patients were treated successfully with endovascular embolization, and the other 2 patients were treated successfully with endovascular embolization followed by surgery. The radiographic abnormalities and presenting symptoms rapidly resolved after dAVF obliteration in all 4 cases. Detailed descriptions of these 4 cases are presented along with a critical review of 15 previously reported cases. In our analysis of these 19 published cases, the following were emphasized: 1) the clinical and radiographic differences between dAVF-induced thalamic versus cortical dementia syndromes; 2) the differential diagnosis and necessary radiographic workup for patients presenting with a rapidly progressive thalamic dementia syndrome; 3) the frequency at which delays in diagnosis occurred and potentially dangerous and avoidable diagnostic procedures were used; and 4) the rapidity and completeness of symptom resolution following dAVF treatment.

Neuroprotective effects of Tilia americana var. mexicana on damage induced by cerebral ischaemia in mice.

Tilia americana var. mexicana (T. americana) is a plant widely used in Mexico for its medicinal properties on the central nervous system. In the present study, we designed a protocol to investigate the neuroprotective effects of non-polar and polar extracts of T. americana on damage induced by cerebral ischaemia in mice. Vehicle or extracts were administered immediately after ischaemia. Functional neurological deficit, survival percentage and infarct area were determined in each experimental group. Results showed that groups treated with non-polar or polar extracts of T. americana had increased survival rate, improved neurological deficits and diminished the infarct area in relation to the ischaemic group. In conclusion, this study confirms the neuroprotective activity of T. americana, suggests a possible synergism between non-polar and polar constituents and supports its potential as a useful aid in the clinical management of stroke.

Traditional Chinese drugs for acute intracerebral hemorrhage:A meta-analysis of randomized controlled trials / 国际中医中药杂志

Objective A large number of traditional Chinese medicine(TCM)are widely used for the treatment of patients with cerebral hemorrhage in China. The aim of this study is to systematically review the existing clinical evidences on TCM treatment for cerebral hemorrhage. Methods Randomized controlled trails(RCTs) of TCM treatment of cerebral hemorrhage were identified, eligible studies were included, the methodological quality of inclusive trails was assessed by the modified Jadad scale. The Cochrane Collaberation’s Revman 5.20 was used for data analysis. Results 69 RCTs were available and included. Meta-analysis indicated that relative risk of overall effective rate of Sanqi, Ciwujia, Chuanxiongqin and Naoxueshu were significant difference; SMD(95% CI) of neural function defect score was SMD=-0.46, 95%CI(-0.56,-0.35)of Sanqi, Danshen, Qingkailing, Liangxuetongyufang;SMD(95%CI) of the reduce of cerebral hemorrhage was SMD = -0.98, 95% CI(-1.32, -0.63)of Danshen, Dahuang, Ciwujia, Qingkailing, Liangxue-Tongyufang. Conclusions The evidence currently available showed that the TCM which included do not increase the death rate and adverse reaction of the patients with cerebral hemorrhage, TCM could reduce neurological deficit and improve the absorption of hematoma.

Dragon's blood dropping pills have protective effects on focal cerebral ischemia rats model.

Dragon's blood is a bright red resin obtained from Dracaena cochinchinensis (Lour.) S.C.Chen (Yunnan, China). As a traditional Chinese medicinal herb, it has great traditional medicinal value and is used for wound healing and to stop bleeding. Its main biological activity comes from phenolic compounds. In this study, phenolic compounds were made into dropping pills and their protective effects were examined by establishing focal cerebral ischemia rats model used method of Middle Cerebral Artery Occlusion (MCAO), and by investigating indexes of neurological scores, infarct volume, cerebral index, cerebral water content and oxidation stress. Compared to model group, high, middle and low groups of Dragon's blood dropping pills could improve the neurological function significantly (p<0.01) and reduce cerebral infarct volume of focal cerebral ischemia rats remarkably (p<0.05-0.01). Meanwhile, each group could alleviate cerebral water content and cerebral index (p<0.05-0.01) and regulate oxidative stress of focal cerebral ischemia rats obviously (p<0.05-0.01). Activities of middle group corresponded with that treated with positive control drug. The results obtained here showed that Dragon's blood dropping pills had protective effects on focal cerebral ischemia rats.

Effect of Acupuncture on Neurological Recovery and Remyelination of Ischemic Focus in Rats with Middle Cerebral Artery Occlusion / 国际脑血管病杂志

Objective:To investigate the protection of acupuncture on damaged myelin sheath from the poinr of view of neurological functional recovery and morphological changes of the myelin sheath.Methods:Eighty-nine adult male Sprague-Dawley rats were randomly allocated to normal (n=5),sham-operation (n=21),model (n=21),early acupuncture (n=21) and late acupancture (n=21) groups.A model of middle cerebral artery occlusion was induced by the intraluminal filament method.Acupuncture was performed at different time points after ischemia.Neurological function and morphological changes of the myelin sheath of ischemic focus were observed by using the methods of neurological deficit scores and Pal-Weigert's myelin staining.Results:Neurological deficit scores at 2.5 hours after the procedure in the model group increased significantly (P＜0.05).qhe scores decreased somewhat as the time elapsed.The internal capsule had obvious demyelination and recovered slowly.Neurological deficit scores in rats at each time point decreased faster in the acupuncture group compared with the model group,and they decreased significantly at day 3 (P＜0.05);the extent of demyelination was significantly alleviated.Neurological deficit scores decreased faster in the early acupuncture group compared with the late acupuncture group (P＜0.05);and demyelination in the early acupuncture group seemed milder at day one.Conclusions:Early acupuncture is beneficial to remyelination and neurological functional recovery after cerebral ischemia.