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17β-estradiol In Ovariectomized Rats With Focal Cerebral Ischemia Neuroprotection And Cognitive Rehabilitation And Its Receptor Mechanism

Posted on:2012-06-28Degree:MasterType:Thesis
Country:ChinaCandidate:X B SongFull Text:PDF
GTID:2154330335981265Subject:Human Anatomy and Embryology
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BackgroundIschemic cerebrovascular disease (isehemia eerebrolvascular disease, ICVD) with high incidence and high mortality and high morbidity, is a serious hazard to human health is one of the major diseases, with the increase in our aging population, lack of The incidence of hemorrhagic cerebrovascular disease continues to increase. Epidemiological studies have shown that premenopausal women than men the same age with low incidence of stroke, and stroke in postmenopausal women was significantly higher. Clinical use of estrogen replacement therapy can make the relative risk of stroke decreased, and stroke-related mortality has also decreased. Study at home and abroad confirm that exogenous estrogen on ovariectomized female rats with focal cerebral ischemia have neuroprotective effects. The therapeutic application of estrogen on the female focal cerebral ischemia in a dose-dependent effects reported are small. At the same time of estrogen on ovariectomized female rats with focal cerebral ischemia in the receptor pathway is still not very clear so far. Foreign scholars study also found that female rats in the model of global cerebral ischemia, 17β-estradiol has neuroprotective effects of cognitive deficits but also can improve symptoms. However, in clinical practice, the incidence of focal cerebral ischemia is much larger than global ischemia, and because of the difference between ischemic way, the path of the different neuronal apoptosis, the disease outcome of nerve damage and cognitive deficits may vary Very far away, so after focal cerebral ischemia model, 17β-estradiol in ovariectomized rats can improve cognitive impairment and its receptor pathway is a problem worthy of study. Objective1. application of 17β-estradiol treatment of ovariectomized rats with focal cerebral ischemia in protective effects in a dose dependent manner.2. Of 17β-estradiol in ovariectomized rats after focal cerebral ischemia may be neuroprotective effect of the receptor pathway.3. The observed therapeutic application of 17β-estradiol in ovariectomized rats with focal cerebral ischemia and whether the cognitive repair and to explore its pathway.Methods1. Longa method using the modified middle cerebral artery occlusion (MCAO) model.2. TTC staining Terms of use of TTC staining brain infarct size measurement.3. Neurological function score Zeal Longa points scoring method used: no neurological deficit was 0; can not be extended to 1 min contralateral forepaw; contralateral rotation for 2 minutes; to the opposite side dump 3 points; no disturbance of consciousness with spontaneous activity for the 4 ; death for 5 minutes. Neurological deficit in each group situation.4. Immunohistochemistry Detection of Erαand Erβprotein expression of 17β-estradiol to ovariectomized female rats with ischemic brain injury possible mechanism.5. HE staining Immunohistochemical observation of the pathological form of adjacent structures, thereby enhancing the persuasiveness of immunohistochemistry.6. Morris water maze test used to assess cognitive function in rats with the status of repairs.7. Statistical data Data presented as mean±standard deviation (±s), said multiple samples were used to compare the number of analysis of variance was used to compare two sample t test. All statistical analysis were to adopt SPSS (17. 0) statistical software to calculate. Results1. Neurological function score24 h after ischemia, A group of neurological function score of each subgroup were lower than C group (P <0.05); A3 group, A1 group of neurological function scores were higher than the A2 group (P <0.05).2. infarct size24 h after ischemia, A sub-group of the volume of cerebral infarction group were significantly lower than C group (P <0.01); in the A group, A1 and A2 significantly between groups (P <0.05), A3 group A2 group with no significant difference between (P> 0.05).3. immunohistochemistryIn normal female SD rats, estrogen receptor ERαand ERβprotein expression of a broad, positive material mainly located in the main nucleus, but can also be detected within the cytoplasm or axons. In the E, F group and the membrane of neurons in the nucleus was detected in the ERαprotein expression, compared with normal brain tissues, its expression was significantly increased (p <0.05). And 24h after ischemia-reperfusion injury, E, F rat hippocampus and cortex of ERβ-positive neurons showed no significant change (p = 0.253 and 0.176).A group of the sub-group average of ERαpositive cells were significantly higher than that of B group (P <0.01); C group, mean ERαpositive cells were significantly higher than that of B group (P <0.05); A1, A2, A3 group ERαbetween the average number of positive cells was no significant difference; and 24h after ischemia-reperfusion injury,A, B group of the hippocampus and cortex the expression of ERβpositive neurons no significant change (P> 0.05).4. Morris water maze testIn the place navigation, as the tests carried out tests for each group 1 day, 2 days to find the latency of the rapid decline leveled off on day 3, maintained at a certain level. Compared with the H group, female rats after focal cerebral ischemia in the event, whether or not given estrogen therapy, and its functions are different degrees of cognitive decline. 6 days before comparing the mean incubation period found in each group, E group F group of rats was significantly shorter than the incubation period, the difference was statistically significant (p = 0.027); Experiments in space exploration, E group the number of rats across the target area, target quadrant swimming time, swimming distance of the target quadrant and other indicators showed no significant change.Conclusions1. 17β-estradiol in ovariectomized rats with focal cerebral ischemia neuroprotection, and in reducing infarct volume has a dose-dependent effect.2. 17β-estradiol in ovariectomized rats with focal cerebral ischemia with cognitive repair.3. Upregulation of ERαmay be involved in the ovariectomized rat focal cerebral ischemic injury in the process of neuroprotection and cognitive rehabilitation;4. ERβmay not be involved in focal cerebral ischemia in ovariectomized rats Neuroprotective and cognitive rehabilitation process.
Keywords/Search Tags:17β-estradiol, cerebral ischemia, neuroprotection, Morris water maze, ERα, ERβ
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