Anti-hematoma expansion time window and establishment of early emergency green channel for intracerebral hemorrhage / 中华神经科杂志

Intracerebral hemorrhage is one of the main causes of death and disability in adults, as a common emergency in neurology department. Hematoma expansion is related to early neurological deterioration and poor outcome in patients with intracerebral hemorrhage. Existing studies have not found effective treatment methods in reducing hematoma expansion. The effective time window of intervention should be paid attention to, and anti-expansion treatments, such as antihypertensive, hemostasis therapy and others, should be performed within the effective time window. The establishment of early emergency green channel for intracerebral hemorrhage is of great significance, to shorten the visiting time of patients with intracerebral hemorrhage and implement effective interventions for anti-hematoma within the anti-hematoma expansion treatment time window.

Mechanical Thrombectomy in Strokes with Large-Vessel Occlusion Beyond 6 Hours: A Pooled Analysis of Randomized Trials

BACKGROUND AND PURPOSE: Mechanical thrombectomy with or without intravenous thrombolysis is indicated in the acute treatment of ischemic strokes caused by an emergent large-vessel occlusion (ELVO) within 6 hours from symptom onset. However, a significant proportion of patients are referred to comprehensive stroke centers beyond this therapeutic time window. This study performed a pooled analysis of data from trials in which mechanical thrombectomy was performed beyond 6 hours from symptom onset. METHODS: We searched for randomized controlled trials that compared mechanical thrombectomy with the best medical treatment beyond 6 hours for ischemic strokes due to ELVO and reported on between 1990 and April 2018. The intervention group comprised patients treated with mechanical thrombectomy. Statistical analysis was conducted while pooling data and analyzing fixed- or random-effects models as appropriate. RESULTS: Four trials involving 518 stroke patients met the eligibility criteria. There were 267 strokes treated with mechanical thrombectomy, with a median time of 10.8 hours between when the patient was last known to be well to randomization. We observed a significant difference between groups concerning the rate of functional independence at 90 days from stroke, with an absolute difference of 27.5% (odds ratio=3.33, 95% CI=1.81–6.12, p < 0.001) and good recanalization (odds ratio=13.17, 95% CI=4.17–41.60, p < 0.001) favoring the intervention group. CONCLUSIONS: This meta-analysis confirms the efficacy of mechanical thrombectomy in selected ischemic stroke patients beyond 6 hours from symptom onset. The selection is mainly based on the limited core infarct detected by emergent assessment using neuroimaging techniques.

Endovascular Mechanical Thrombectomy in Basilar Artery Occlusion: Initial Experience

OBJECTIVE: This study was conducted to assess the efficacy and safety of endovascular mechanical thrombectomy (EMT) for patients diagnosed with basilar artery (BA) occlusion. MATERIALS AND METHODS: We retrospectively analyzed clinical and imaging data of 16 patients diagnosed with BA occlusion who were treated with endovascular intervention from July 2012 to February 2013. Direct suction using the Penumbra system and thrombus retrieval by the Solitaire stent were the main endovascular techniques used to restore BA flow. The outcomes were evaluated based on rate of angiographic recanalization, rate of improvement of National Institutes of Health Stroke Scale (NIHSS) score, rate of modified Rankin Scale (mRS) at discharge and after 3 months, and rate of cerebral hemorrhagic complications. Successful recanalization was defined as achieving Thrombolysis In Cerebral Infarction (TICI) of II or III. RESULTS: Sixteen patients received thrombectomy. The mean age was 67.8 +/- 11 years and the mean NIHSS score was 12.3 +/- 8.2. Eight patients treated within 6 hours of symptom onset were grouped as A and the other 8 patients treated beyond 6 hours (range, 6-120) were grouped as B. Successful recanalization was met in six patients (75%) for group A and 7 (87.5%) for group B. Favorable outcome occurred in 4 patients (50%) for group A and 5 (62.5%) for group B. CONCLUSION: Our study supports the effectiveness and safety of endovascular mechanical thrombectomy in treating BA occlusion even 6 hours after symptom onset.

Endovascular Mechanical Thrombectomy in Basilar Artery Occlusion: Initial Experience

OBJECTIVE: This study was conducted to assess the efficacy and safety of endovascular mechanical thrombectomy (EMT) for patients diagnosed with basilar artery (BA) occlusion. MATERIALS AND METHODS: We retrospectively analyzed clinical and imaging data of 16 patients diagnosed with BA occlusion who were treated with endovascular intervention from July 2012 to February 2013. Direct suction using the Penumbra system and thrombus retrieval by the Solitaire stent were the main endovascular techniques used to restore BA flow. The outcomes were evaluated based on rate of angiographic recanalization, rate of improvement of National Institutes of Health Stroke Scale (NIHSS) score, rate of modified Rankin Scale (mRS) at discharge and after 3 months, and rate of cerebral hemorrhagic complications. Successful recanalization was defined as achieving Thrombolysis In Cerebral Infarction (TICI) of II or III. RESULTS: Sixteen patients received thrombectomy. The mean age was 67.8 +/- 11 years and the mean NIHSS score was 12.3 +/- 8.2. Eight patients treated within 6 hours of symptom onset were grouped as A and the other 8 patients treated beyond 6 hours (range, 6-120) were grouped as B. Successful recanalization was met in six patients (75%) for group A and 7 (87.5%) for group B. Favorable outcome occurred in 4 patients (50%) for group A and 5 (62.5%) for group B. CONCLUSION: Our study supports the effectiveness and safety of endovascular mechanical thrombectomy in treating BA occlusion even 6 hours after symptom onset.

Influence of EA at different therapeutic time windows on the expression of HSP70 and nervous cell apoptosis after focal cerebral ischemic reperfusion injury in rats / 国际中医中药杂志

Objective To observe the influence of electroacupuncure(EA) at different therapeutic time windows on the effects of inosine on neuronal apoptosis and expression of heat-shock-proteins-70 (HSP70)after focal cerebral ischemic reperfusion injury (CIRI) in rats.Methods The model was established by ligation of the artery for 2 hour.EA was delivered to “baihui” and “dazhui” through acupuncture needles 0.5 hr,2 hr,6 hr and 12 hr respectively following MCAO.The expression level of HSP70 and the number of apoptotic cells were examined by immunohistochemical technique and TUNEL,comparing the average optical density of HSP70 and the number of apoptotic positive cells of cortex penumbra and hippocampus CA1 area in rat brain.Results Compared with the model group,the average optical density of HSP70 in every EA group was increased in apoptotic positive cells of cortex penumbra and hippocampus CA1 area 0.5 h (89.98± 6.55),(128.73 ± 8.03),2 h (90.96±6.38),(132.25±8.78),6 h (93.71±6.12),(132.58±7.04),12 (96.19±7.30),(133.57±6.19)and the number of apoptotic positive cells of cortex penumbra in every EA group was decreased 0.5 h (1.80±0.84),2 h (3.40± 1.14),6 h (5.00± 1.00),12 h (5.00±2.45).The number of apoptotic cells of hippocampus CA1 area was decreased just in the EA group of 0.5 h (1.60± 1.89).Conclusion EA could increase the expression level of HSP70 and at the same time decrease the number of apoptotic cells,EA plays an important part in protecting the neuronal cells of brain after focal cerebral ischemic reperfusion injury.The acupuncture treatment should be taken as far as early.

Neuroprotection by Valproic Acid in Mouse Models of Permanent and Transient Focal Cerebral Ischemia

Valproic acid (VPA) is a well-known anti-epileptic and mood stabilizing drug. A growing number of reports demonstrate that VPA is neuroprotective against various insults. Despite intensive efforts to develop new therapeutics for stroke over the past two decades, all treatments have thus far failed to show clinical effect because of treatment-limiting side effects of the drugs. Therefore, a safety-validated drug like VPA would be an attractive candidate if it has neuroprotective effects against ischemic insults. The present study was undertaken to examine whether pre- and post-insult treatments with VPA protect against brain infarct and neurological deficits in mouse transient (tMCAO) and permanent middle cerebral artery occlusion (pMCAO) models. In the tMCAO (2 hr MCAO and 22 hr reperfusion) model, intraperitoneal injection of VPA (300 mg/kg, i.p.) 30 min prior to MCAO significantly reduced the infarct size and the neurological deficit. VPA treatment immediately after reperfusion significantly reduced the infarct size. The administration of VPA at 4 hr after reperfusion failed to reduce the infarct size and the neurological deficit. In the pMCAO model, treatment with VPA (300 mg/kg, i.p.) 30 min prior to MCAO significantly attenuated the infarct size, but did not affect the neurological deficit. Western blot analysis of acetylated H3 and H4 protein levels in extracts from the ischemic cortical area showed that treatment with VPA increased the expression of acetylated H3 and H4 at 2 hrs after MCAO. These results demonstrated that treatment with VPA prior to ischemia attenuated ischemic brain damage in both mice tMCAO and pMCAO models and treatment with VPA immediately after reperfusion reduced the infarct area in the tMCAO model. VPA could therefore be evaluated for clinical use in stroke patients.

Therapeutic time window of dimethylaminoethyl ginkgolide B mesylate in permanent focal ischemia of rat / 中国药科大学学报

In order to study the therapeutic time window of dimethylaminoethyl ginkgolide B mesylate(XQ-1H) in the permanent focal ischemia of rat,we used the rat model of the permanent middle cerebral artery occlusion (pMCAO).Doses of 15.6,7.8 and 3.9 mg/kg of XQ-1 H were intravenously administered at 0.5,1,2,3 h after MCAO,respectively.Neurological scores,infarct sizes,water contents and pathological changes in each interval were determined at 72 h after MCAO.It was observed that XQ-1 H administered at 0.5 and 1 h after MCAO significantly reduced the cerebral infarct size and edema,and produced significant reductions in the neurological deficits.The protective effect of XQ-1H on the neuron cells was proved by pathological observations.In addition,the contents of MDA,lactate,and the activities of SOD were measured.Reduction in the contents of MDA and lactate and enhancement in the activities of SOD were attributed to the pretreatment of XQ-1H at 0.5 and 1 h.Our results showed that the therapeutic time window of XQ-1H extended for up to 1 h after MCAO.

Therapeutic time window for methylprednisolone in spinal cord injured rat

Recent clinical trials have reported that methylprednisolone sodium succinate administered within 8 hours improves neurological recovery in human spinal cord injury (SCI). Methylprednisolone, however, was ineffective and possibly even deleterious when given more than 8 hours after injury. This finding suggests that a therapeutic time window exists in spinal cord injury. In order to determine the doses, durations and timing of methylprednisolone treatment for optimal neuroprotection, a single or two bolus dose of methylprednisolone (30 mg/kg) was administered at 10, 30, 120, 150 and 240 min. after three graded spinal cord injury. The primary outcome measure was 24-hour spinal cord lesion volumes estimated from spinal cord Na+ and K+ shifts. A single 30 mg/kg dose of methylprednisolone at 10 min. after injury significantly reduced 24-hour lesion volumes in injured rat spinal cords. However, any other methylprednisolone treatment starting 30 min. or more after injury had no effect on 24-hour lesion volumes compared to the vehicle control group. Moreover, delayed treatment increased lesion volumes in some cases. These results suggest that the NYU SCI model has a very short therapeutic window.