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Objective ToobservetheeffectsofNaokangⅡ,atraditionalChinesemedicineon spatial learning and memory abilities and hippocampal neurogenesis in rats with cerebral ischemia. Methods Atotalof54SDratsweredividedinto6groupsaccordingtothedigitalrandommethod:a control,a sham operation,a model,a low-dose,a medium-dose,and a high-dose NaokangⅡ group (the low-,medium-,and high-dose groups were 5,10,and 20 times of adults (n=9 in each group). A rat model was induced by ligate the bilateral common carotid arteries permanently. The bilateral common carotid arteries were only isolated but not ligated in rats of the sham operation group. The rats in the control group were not given any treatment. After modeling,the rats in the treatment groups were treated with NaokangⅡ. The rats in the control,sham operation,and model groups were given equal volume of isotonic saline (2 ml). Morris water maze test and space search experiment were used to evaluate the learning and memory abilities in rats 9 weeks after modeling. Immunofluorescence staining and immunohistochemical methods were used to observe proliferation and differentiation of neural stem cells (NSCs). Western blot was used to detect the expression of autophagy related protein Beclin-1 and LC-3Ⅱ. Results (1 )The escape latencies of the model group from 1 to 5 days were 100 ± 13,98 ± 13,82 ± 14,72 ± 15,and 46 ± 7 s,respectively. They were significantly longer than those of the sham operation group and the control group (all P<0. 05). The search distances were 1239 ± 127,1011 ± 122,959 ± 123,553 ± 66,and 407 ± 29 cm,respectively. They were significantly increased as compared with those of the sham operation group and control group (all P<0. 01). Both the escape latencies and search distances of the rats in the Naokang Ⅱ low-,medium-,and high-dose groups were significantly shorter than those of the model group (P<0. 05). The escape latencies on the fifth day were 20 ± 6,19 ± 8,and 15 ± 6 s,respectively,and the search distances were 234 ± 38, 297 ± 23,and 99 ± 22 cm,respectively. Nine weeks after modeling,the quadrant search time on the original platform in the rats of the model group was 30 ± 9 s,it was significantly shorter than that of the sham operation group (P<0. 01). The quadrant search time on the original platform of the Naokang Ⅱ low-, medium-,and high-dose groups were 34 ± 6,38 ± 8,and 40 ± 10 s,respectively. They were significantly longer than those of the model group (P <0. 01). (2)Nine weeks after modeling,the results of immunofluorescence and immunohistochemistry showed that the number of BrdU-positive cells and the Nestin positive cells in hippocampal dentate gyrus of the model group were higher than those of the control group and the sham operation group (P<0. 05). The number of BrdU-positive cells and Nestin positive cells of Naokang Ⅱ each dose group were significantly higher than those of the model group (P<0. 05). The expression of LC-3Ⅱand Beclin-1 in the model group was significantly higher than those in the control and sham operation groups (P<0. 01). The expression of LC-3Ⅱ in the medium- and high-dose groups was 143 ± 9 and 129 ± 9 respectively,and the expression of Beclin-1 was 139 ± 10 and 124 ± 7 respectively, andtheyweresignificantlylowerthanthemodelgroup(P<0.01).Conclusion NaokangⅡcanimprove the cognitive function in rats with cerebral ischemia,promote neurogenesis in the dentate gyrus,and inhibit autophagic cell death.
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ObjectiveTo investigate the effect of sevoflurane anesthesia in the neonatal period on cognitive function and acetylcholinesterase(AChE) activity in hippocampus in developmental stages in rats.Methods Eighty 7 day-old SD rats weighing 12-16 g were randomly divided into 5 groups( n ＝ 16 each):groups A and B inhaled 3 ％ sevoflurane in oxygen for 6 and 2 h respectively; groups C and D inhaled 1.5 ％ sevoflurane in oxygen for 6 and 2 h respectively; group E inhaled oxygen only.The cognitive function was assessed using Morris water maze test in weaning period(16-21 day-old) and sexual maturity period (55-60 day-old) respectively.The rats were sacrificed at 30 min after Morris water maze test was finished at 21 and 60 d after birth,and the hippecampus were removed for determination of AChE activity using colorimetry method.ResultsCompared with group E,escape latency was prolonged during 17-20 d after birth in group A,and at 18,19 d after birth in groups B and C,and at 18 d after birth in group C,and AChE activity increased at 21 d after birth in group A( P < 0.05 or 0.01 ).Compared with group A,escape latency was shortened at 19,20 d after birth,and AChE activity decreased at 21 d after birth in groups B and C( P < 0.05 or 0.01).Compared with groups B and C,escape latency was shortened at 19,20 d after birth in group D( P < 0.05).There were no significantly differences in probe time in original platform quadrant,frequency of crossing the original platform and AChE activity at 60 d after birth and escape latency during sexual maturity period among the 5 groups( P ＞ 0.05).ConclusionSevoflurane anesthesia in the neonatal period can reversible decrease the congnitive function in developmental stages in rats in concentration and time dependent manners,and the mechanism may be related to increasing the AChE activity in hippocampus.
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Objective To investigate the relationship of lacunar infarction (LI) and white matter lesion with cognitive impairment in patients with subcortical ischemic vascular disease (SIVD) Methods Fifty-three patients were diagnosed as SIVD according to the criteria of Erkinjuntti. The symptoms and signs were recorded by an interview and examination, and neuropsychological assessment and magnetic resonance imaging (MRI) were performed. A semi-automated MRI quantitative method was used to measure the volume of white matter hyperintensity (WMH) and the number of LI was counted. Correlation and the partial correlation analysis were performed to examine the relationship of general cognitive function with the volume of WMH and the number of LI. Results The pseudobulbar paralysis symptom and the upper motoneuron injury sign were the most common in these patients (18.9% and 37.7%). Correlation analysis showed that there was positive correlation between the volume of WMH and age (r = 0. 518, P < 0. 05), and there was negative correlcction between mini-metal state examination (MMSE) scures and the volume of WMH (r=-0.514, P<0. 05), After controlling confounding factors, only age was positively correlated with the volume of WMH (r=0. 400, P=0. 004). There were negative correlation between the number of LI, the volume of WMH and MMSE scores(r=-0. 456,-0. 514,-0. 385,-0. 382;all P<0. 05), and the years of education was positively correlated with MMSE scores (r= 0. 518, P< 0. 001). Conclusions Age may not be the main risk factor for cognitive impairment in patients with SIVD. The volume of WMH and the number of LI are independent risk factors for cognitive impairment in patients with SIVD. Patients with severer SIVD or more LI show poorer performance on cognitive function.
ABSTRACT
White matter lesions on neuroimaging are common in the normal aged and in patients with several cognitive disorders. Its pathological features include demyelination, axonal loss and lacunar infarction, and the pathophysiological mechanisms may be chronic cerebral ischemia caused by hypoperfusion and disturbance of cerebral blood flow disorders. Vascular white matter lesiom may cause different degrees of cogntive disorders, but the exact the pathological subtype of dementia associated with white matter lesions remains uncertain.