ABSTRACT
Induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) hold great promise as a cell source for transplantation into injured tissues to alleviate inflammation. However, the therapeutic efficacy of iMSC transplantation for ischemic stroke remains unknown. In this study, we evaluated the therapeutic effects of iMSC transplantation on brain injury after ischemia-reperfusion using a rat transient middle cerebral artery occlusion model and compared its therapeutic efficacy with that of bone marrow mesenchymal stem cells (BMMSCs). We showed that iMSCs and BMMSCs reduced infarct volumes after reperfusion and significantly improved motor function on days 3, 7, 14, 28, and 56 and cognitive function on days 28 and 56 after reperfusion compared with the vehicle group. Furthermore, immunological analyses revealed that transplantation of iMSCs and BMMSCs inhibited microglial activation and expression of proinflammatory cytokines and suppressed oxidative stress and neuronal cell death in the cerebral cortex at the ischemic border zone. No difference in therapeutic effect was observed between the iMSC and BMMSC groups. Taken together, our results demonstrate that iMSC therapy can be a practical alternative as a cell source for attenuation of brain injury and improvement of neurological function because of the unlimited supply of uniform therapeutic cells.
ABSTRACT
OBJECTIVE：To study the improvement effects of icariside Ⅱ（ICS Ⅱ）on neurological function of focal cerebral ischemia model rats by regulating miR- 141-3p/Notch/nuclear factor erythroid- 2-related factor 2（Nrf2）axis（miR-141-3p/Notch/ Nrf2）. METHODS ：The rats were divided into sham operation group ，model group ，nimodipine group （20 mg/kg）and ICS Ⅱ low-dose，medium-dose and high-dose groups （4，8，16 mg/kg），with 20 rats in each group. Twenty-four hours after establishing focal cerebral ischemia model ，model rats were given re levant medicine or normal saline intragastrically ，twice a day ，for consecutive 3 d. The neurological deficit of rats in each group was scored ；the volume of cerebral infarction was measured by 2，3， 5-triphenyltetrazolium chloride （TTC）staining；water content of cerebral tissue and the permeability of blood-brain barrier were measured；HE staining was performed to observe the pathological change of cerebral tissue of rats ；the expression of miR- 141-3p in cerebral tissue of rats was measured by qRT-PCR ；the protein expression of Notch and Nrf 2 in cerebral tissue of rats were measured by Western blotting assay. RESULTS ：Compared with sham operation group ，the neurological deficit score ，expression of Notch-1 and Nrf 2 in model group were significantly lowered （P＜0.05）；infarction volume ，brain water content ，the permeability of blood-brain barrier and the expression of miR- 141-3p in cerebral tissue were increased significantly （P＜0.05）；the distribution of cortical cells was disordered ，and inflammatory infiltration and necrosis were observed in a large number of nerve cells. Compared with model group ，the neurological deficit score ，the protein expression of Notch- 1 and Nrf 2 in cerebral tissue were significantly increased in ICS Ⅱgroups（P＜0.05）；infarction volume ，brain water content ，the permeability of blood-brain barrier and the expression of miR- 141-3p in cerebral tissue were decreased significantly （P＜0.05）；the arrangement of cortical cells was regular，and the inflammatory infiltration and necrosis of nerve cells were decreased significantly. CONCLUSIONS ：ICS Ⅱ can promote the recovery of neurological function in focal cerebral ischemic model rats ，which may be related to down-regulation of miR-141-3p and activation of Notch/Nrf 2 axis.
ABSTRACT
Objective To investigate the establishment of focal cerebral ischemia model in rabbits with the improved suture method.Methods A total of 45 healthy and clean adult New Zealand rabbits were divided into either a sham operation group (n =5) or a model group (n =40) using random number table method before modeling,and the sex was not limited.The self-made head ends of 2-0 fishing lines dipped in paraffin were used as the sutures.The external carotid artery was cut and inserted into a intracranial artery through the internal carotid artery and blocked the origin of middle cerebral artery.The neurological function score was performed after 6 h.The neurological deficit scores ≥2 was successful modeling.The rabbits were killed by anesthesia.The brain slices were stained with 2％ 2,3,5-triphenyl tetrazolium chloride solution.The infarct foci were observed.The diameters of suture head and the depth of suture insertion were compared in the model rabbits with successful modeling,failure,and death in the model group.Results There were 40 rabbits in the model group,six of them died,including 4 died of subarachnoid hemorrhage within 4 h after operation,and 2 died from anesthetic accident.The mortality rate was 15.0％.Seven rabbits failed,mainly because of cerebral vasospasm and the insertion depth of suture was insufficient.Twenty-seven had successful modeling,and the success rate was 67.5％.All the rabbits in the sham operation group survived.The diameter of the suture head and insertion depth in the successful modeling rabbits were compared with the death and failure outcome in rabbits.The difference was statistically significant (diameter:0.52 ± 0.14 mm vs.0.45 ±0.40 mm and 0.58 ±0.17 mm;depth:5.49 ±0.17 cm vs.6.04 ± 0.11 cm and 4.26 ±0.30 cm;all P ＜ 0.05).Conclusions The improved suture method can successfully prepare the focal cerebral ischemia model of middle cerebral artery in rabbits.The method is simple.Its repeatability and practicability are better.
ABSTRACT
@#There are many ways to prepare middle cerebral artery occlusion (MCAO) rat model. The focal cerebral ischemia model es-tablished by the suture-occluded method is widely accepted as an ideal focal cerebral ischemia model, which can be used in the basic and clinical study of cerebral vascular diseases. However, it still has the defects of high technical requirement, large model difference and high animal mortality. A variety of focal cerebral ischemia models were established by changing the retention time of the thread, the road the thread plugging into, the type of thread bolt and the depth of the thread plugging. This article compared different suture-occluded method, as well as the suture-occluded method to other modeling methods, different cerebral ischemia models may be different in the pathophysiology of cerebral infarction, and the effects may also be different.
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@#Objective To compare and evaluate the efficacy of three operating procedures to produce permanent rat models of cerebral ischemia, including mortality, neurological evaluation score, infarction volume of ischemia and time consumed in the operation. Methods The rats were randomly divided into three groups. Group 1: The common carotid artery (CCA) and external carotid artery (ECA) were ligated during the operation and ICA was clipped temporarily by artery clamp. Group 2: The CCA and ECA were ligated and the superior thyroid artery and pterygopalatine artery were exposed but not ligated. Silk suture was utilized to hang the internal carotid artery (ICA). Plastic suture was inserted into ICA and stepped over the initiation point of pterygopalatine artery under microscopic observation. Group 3: The CCA and ECA were ligated and ICA was hanged with a silk suture, and the pterygopalatine artery was not exposed, but during the period of inserting plastic suture, the proximal part of the suture was pressed to make the suture's round distal end elevated, and then pass the initial point of pterygopalatine artery. Mortality, neurological score, volume of ischemic infarction and operation time consumed of the three groups were compared after the operation. Results The procedure to prepare the model was most efficient in the group 3, taking only 17.5 min to complete, significantly less than that in the group 1 (50 min) and group 2 (40 min), (P<0.05), and with a lower mortality and more steady neurological evaluation score and infarction volume. Conclusion The use of the third operating method can shorten the operation time and improve the efficacy of operation. Using this method, more consistent and repetitive focal cerebral ischemia models can be produced effectively, and meet the demands of clinical trials.
ABSTRACT
Middle cerebral artery occlusion(MCAO) can be used to establish the standard model of focal cerebral ischemia.The method for establishing focal cerebral ischemia model has been improved continuously,from simple behavior score,measurement of infarcted brain area,and morphological observation in the past to functional study,neurobiochemistry,molecular biology,etc.The research of MCAO provides a basis for further study of the pathological characteristics,mechanism and prevention of human cerebral ischemia.This article reviews the recent advancement in the study of MCAO model and cerebral(ischemia.)
