Local mild hypothermia with thrombolysis for acute ischemic stroke within a 6-h window

Ministry of Science and Technology of China [2004BA71406-2]; Xiamen Health Bureau [WZK0608]Objective: To determine the safety and efficacy of combined local mild hypothermia and IV rtPA in treating acute ischemic stroke (AIS) patients with MRI perfusion- and diffusion-weighted imaging (PWI/DWI) mismatch within a 6-h stroke window. Methods: AIS patients within 6 h of a minimum 20% PWI/DWI MRI mismatch were randomly assigned to 3 groups: local mild hypothermia with IV rtPA (Group A); IV rtPA (Group B); or conventional anti-platelet aggregation (Group C). Mortality and National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS) score and Barthel Index (BI) were used in evaluation. Results: There were significant differences in NIHSS 24h after treatment among the three groups (P < 0.001). Based on mRS and BI, more patients in Groups A and B showed favorable outcomes than patients in Group C (P = 0.017 and P = 0.009, respectively); however, there were no significant efficacy differences between Groups A and B. The incidence of symptomatic ICH and the mortality rates within 90 days in the 3 groups were similar. In addition, there were no significant differences in NIHSS improvement at 24h and favorable outcomes 90 days after IV rtPA treatment between patients within 3 h and 3-6 h from symptom onset. Conclusions: There was no benefit of combined local hypothermia/IV rtPA treatment compared to IV rtPA alone. PWI/DWI mismatching on MRI can be a selection criteria for IV rtPA treatment within a 6-h window. (C) 2011 Elsevier B.V. All rights reserved

Changes in cerebral glucose metabolism in patients with mild-to-moderate Alzheimer's disease: A pilot study with the Chinese herbal medicine fuzhisan

National Natural Science Foundation of China [30670726]; Nature Science Foundation of HeiLongjiang [ZJY03-5]The aim of this study was to investigate the effects of fuzhisan (FZS, 10 mg/day), a Chinese herbal medicine, on cerebral glucose metabolism and neuropsychological metrics in patients with mild-to-moderate Alzheimer's disease (AD). This was a 12-week, randomized, double-blind, placebo-controlled pilot study. Twenty-two subjects were randomly assigned to groups that received FZS (n = 12) or placebo (n = 10). Positron emission tomography (PET) was used to study the regional cerebral metabolic rate of glucose consumption (rCMRglc) at baseline and week 12. We evaluated the clinical efficacy of FZS on cognition and behavioral functions using the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) and the Neuropsychiatric Index (NPI), respectively. Compared with placebo, FZS significantly improved ADAS-Cog scores and NPI scores at week 12. Moreover, FZS treatment favorably improved rCMRglc in the bilateral temporal and parietal cortices, hippocampus, and posterior cingulate gyrus. These results suggest that FZS treatment may have a positive effect on cognition, behavioral functions, and rCMRgIc in mild-to-moderate AD patients. (C) 2011 Elsevier Ireland Ltd. All rights reserved

The combination therapy increased the expression of VEGF in ischemic regions.

<p>A. The expression of VEGF was determined by immunofluorescence. B. The expression of VEGF was measured by western blot. (A: sham-surgery group; B:model group; C:BMSCs group; D:MH group; E:combination therapy group.) Values are expressed as mean± SE. n = 3. *P < 0.05, compared to control; ^#P<0.05, compared with the combined therapy group.</p

The combination therapy increased angiogenesis in ischemic regions.

<p>Microscopic images of the temporal cortex in coronal sections stained with anti-RECA-1 antibody. The arrows indicate RECA-1 positive microvessels. A. The microvessels (RECA-1 positive structures) were examined within the temporal cortex under × 100 magnification. B. Quantification of microvessels is expressed as microvessel density (number of stained vessels per microscopic field). Data are expressed as mean± S.E. n = 3.</p

The mNSS scores of rats.

<p>The mNSS scores of rats.</p

Bone mesenchymal stem cells transplantation combined with mild hypothermia improves the prognosis of cerebral ischemia in rats

<div><p>Bone marrow mesenchymal stem cells (BMSCs) are used as a great promising choice for the treatment of cerebral ischemia. Herein, we discuss the neuroprotective effects of the combination of BMSCs transplantation and mild hypothermia (MH) in an ischemia-reperfusion rat model. First, BMSCs were isolated using density gradient centrifugation and the adherent screening method, followed by culture, identification and labeling with DAPI. Second, adult male SD rats were divided into 5 groups: sham group (surgery without blockage of middle cerebral artery), model group (middle cerebral artery occlusion (MCAO) was established 2h prior to reperfusion), BMSCs group (injection of BMSCs via the lateral ventricle 24h after MCAO), MH group (mild hypothermia for 3h immediately after MCAO) and combination therapy group (combination of BMSCs and MH). Finally, the modified neurological severity score (mNSS) test was performed to assess behavioral function at different time points (before MCAO, before transplantation, at day 1, day 5 and day 10 after transplantation). After that, the brain was subjected to TTC staining, and the homing and angiogenesis were evaluated by immumofluorescence and immunohistochemistry. Immunofluorescence staining and Western Blot analysis were performed to calculate the percentage of the infarct area and explore glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF). Our results showed that the combination therapy significantly decreased mNSS scores (P<0.01) and reduced the percentage of the infarct area (P<0.01) than a single treatment. Moreover, the expression of GFAP and VEGF increased significantly in the combination therapy group (at day 5, day 10 after transplantation; at all time points after transplantation, respectively) compared to the single treatment groups. Taken together, it was suggested that the combination of BMSCs transplantation and MH can significantly reduce the percentage of the infarct area and improve functional recovery by promoting homing and angiogenesis, which may be a beneficial treatment for cerebral ischemia.</p></div

Bone mesenchymal stem cells transplantation combined with mild hypothermia improves the prognosis of cerebral ischemia in rats - Fig 3

<p>The combination therapy increased the expression of GFAP in ischemic regions A. The expression of GFAP was determined by immunofluorescence. B. The expression of GFAP was measured by western blot. (A: sham-surgery group; B:model group; C:BMSCs group; D:MH group; E:combination therapy group.) Values are expressed as mean± SE. n = 3. *P < 0.05, compared to control; ^#P<0.05, compared with the combined therapy group.</p

Variation tendency of rats mNSS scores.

<p>Neurological functional tests were performed in each group at each time point (n = 6), respectively. The rats mNSS scores in the combination therapy group decreased more obviously than that in the BMSCs group. Values are expressed as mean± SE. *P < 0.05, compared to control; ^#P<0.05, compared with the combined therapy group.</p

The percentage of infarction size of rats.

<p>The percentage of infarction size of rats.</p