Brain Ischemia ; metabolism ; pathology ; prevention & control ; Humans ; Ischemic Preconditioning ; methods ; Myocardial Reperfusion Injury ; metabolism ; pathology ; prevention & control ; Reperfusion Injury ; metabolism ; pathology ; prevention & control

Cerebral ischemia-reperfusion injury(CIRI) is an important factor hindering the recovery of ischemic stroke patients after blood flow recanalization. Mitochondria, serving as the "energy chamber" of cells, have multiple important physiological functions, such as supplying energy, metabolizing reactive oxygen species, storing calcium, and mediating programmed cell death. During CIRI, oxidative stress, calcium overload, inflammatory response, and other factors can easily lead to neuronal mitochondrial dyshomeostasis, which is the key pathological link leading to secondary injury. As reported, the mitochondrial quality control(MQC) system, mainly including mitochondrial biosynthesis, kinetics, autophagy, and derived vesicles, is an important endogenous mechanism to maintain mitochondrial homeostasis and plays an important protective role in the damage of mitochondrial structure and function caused by CIRI. This paper reviewed the mechanism of MQC and the research progress on MQC-targeting therapy of CIRI in recent 10 years to provide theoretical references for exploring new strategies for the prevention and treatment of ischemic stroke with traditional Chinese medicine.
Brain Ischemia/prevention & control* ; Calcium/metabolism* ; Humans ; Ischemic Stroke ; Mitochondria/pathology* ; Reactive Oxygen Species/metabolism* ; Reperfusion Injury/prevention & control*

OBJECTIVETo observe the protective effect of verapamil pretreatment against cerebral ischemia-reperfusion injury in gerbils.

METHODSThirty-three Mongolian gerbils were randomized into the control group (group A, n=6, with sham operation), ischemia group (group B), and 3 verapamil groups (groups C, D, and E, n=7) with intraperitpneal verapamil injection (2 mg/kg) 48, 24 and 12 h before ischemia, respectively. In group A, the bilateral common carotid arteries were only exposed without clamping, and in the other 4 groups, the arteries were clamped for 20 min followed by reperfusion for 50 min. The gerbils were then decapitated and the forebrain cerebral cortex was removed to determine superoxide dismutase (SOD) and glutathione (GSH) activities and measure the contents of malondial dehyde (MDA), endothelin (ET) and calcitonin gene-related peptide (CGRP). The left forebrain cerebral cortex was sampled in each group to observe the ultrastructural changes under electron microscope.

RESULTSIn groups C and D, SOD activities were significantly higher than those in group B (P<0.05), and in group E, the SOD activity elevation was not statistically significant (P>0.05). In groups C, D and E, GSH activity was significantly higher than that in group B (P<0.05). MDA content was significantly lower in groups C and D than in group B (P<0.05), but comparable between groups E and B (P>0.05). ET content was also significantly lower in the pretreatment groups (P<0.05), but CGRP content higher (not statistically so, however) than those in group B. The more serious ultrastructural damage of the cerebral tissue was observed in group B, but only mild damage was found in the verapamil groups.

CONCLUSIONSVerapamil given 12-48 h before cerebral ischemia may protect the gerbils from cerebral ischemia-reperfusion injury by enhancing SOD, GSH activities and decreasing ET content.

Animals ; Brain ; drug effects ; metabolism ; pathology ; Brain Ischemia ; complications ; metabolism ; pathology ; prevention & control ; Endothelins ; metabolism ; Gerbillinae ; Glutathione ; metabolism ; Malondialdehyde ; metabolism ; Receptors, Calcitonin Gene-Related Peptide ; metabolism ; Reperfusion Injury ; complications ; metabolism ; pathology ; prevention & control ; Superoxide Dismutase ; metabolism ; Verapamil ; pharmacology

Animals ; Astrocytes ; metabolism ; Brain Ischemia ; metabolism ; pathology ; Glial Fibrillary Acidic Protein ; metabolism ; Neuroprotective Agents ; pharmacology ; Propofol ; pharmacology ; Random Allocation ; Rats ; Rats, Wistar ; Reperfusion Injury ; metabolism ; prevention & control

OBJECTIVETo investigate the protective effect of leptin against cerebral ischemia/reperfusion injury in mice.

METHODSMouse models of transient focal cerebral ischemia were established by occlusion of the right middle cerebral artery for 2 h followed by 24 h reperfusion. The infarct volume and neurological deficit scores following leptin treatment were determined using TTC staining and the Longa's score, respectively, to evaluate the protective effect of leptin against ischemic cerebral injury. The levels of lactate dehydrogenase (LDH), malondialdehyde (MDA) and nitric oxide (NO) in the brain tissue were measured by colorimetry. The histopathological changes in the brain were observed with HE staining, and the expression of glial fibrillary acidicprotein (GFAP) was detected by immunohistochemistry.

RESULTSLeptin treatment markedly reduced cerebral infarct volume and neurological deficits induced by transient ischemia. The LDH, MDA and NO levels in the brain tissues were significantly decreased after leptin treatment, which also alleviated the histopathological injury, maintained the normal morphology of the astrocytes and increased the expression of GFAP.

CONCLUSIONLeptin produces obvious protective effect against cerebral ischemia/reperfusion injury by inhibiting lipid peroxidation, stabilizing the internal environment and adjusting the activity of the astrocytes.

Animals ; Brain ; drug effects ; pathology ; Brain Ischemia ; Infarction, Middle Cerebral Artery ; metabolism ; pathology ; L-Lactate Dehydrogenase ; metabolism ; Leptin ; pharmacology ; Male ; Malondialdehyde ; metabolism ; Mice ; Nitric Oxide ; metabolism ; Reperfusion Injury ; metabolism ; pathology ; prevention & control ; Time Factors

Animals ; Brain Edema ; prevention & control ; Brain Ischemia ; physiopathology ; Erythropoietin ; pharmacology ; Female ; Hippocampus ; metabolism ; pathology ; Male ; Nitric Oxide ; metabolism ; Protective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; prevention & control ; Superoxide Dismutase ; metabolism

OBJECTIVETo investigate the neuroprotective effect of basic fibroblast growth factor (bFGF) on neurological function after hypoxic-ischemic brain damage (HIBD) in neonatal rats.

METHODSNinety-six HIBD models of neonatal Wistar rats were made by shearing right arteria carotis communis and then breathing 8% O(2)+92%N(2) for two hours. The models were divided into two groups randomly: the bFGF trial group and the normal saline control group. Each group had forty-eight rats. The other forty-eight neonatal Wistar rats were taken into the sham operation group. Forty rats were taken from each group and sacrificed on the 4 th, 7 th, 10 th, 17 th and 24 th days after the operation, respectively, The pathological changes in the brain were observed by optical microscope and the expressions of nestin and growth-associated protein-43 (GAP-43) in hippocampal CA1 region were examined with immunohistochemical staining and image quantitative analysis on the 4 th, 7 th, 10 th, 17 th and 24 th days after the operation. The spatial cognitive capability of other eight rats which were taken from each group respectively was evaluated by using the Morris water maze at the age of 30 days.

RESULTS(1) No brain damage was found in the sham operation group, the neurocytes were degenerative and necrotic in the control group of normal saline. The pathological manifestation of the brain damage in the bFGF trial group was milder than that of the normal saline control group. (2) Expression of nestin: The number of nestin-positive cells in hippocampal CA1 region of control group on the 4 th, 7 th, 10 th, 17 th and 24 th days after the operation was significantly increased compared with that of the sham operation group at all time points, and the numbers of nestin-positive cells in hippocampal CA1 region of the trial group were higher than those of the sham operation group and the control group (P < 0.01). (3) The expression of GAP-43 in hippocampal CA1 region of the neonatal rats reached peak on the 10th day after the operation in all the three groups. The integral optical density (IOD) of GAP-43 in hippocampal CA1 region of the control group was higher than that of the sham-operation group at all time points, and the IOD of GAP-43 in hippocampal CA1 region of the trial group was higher than those of the sham operation group and the control group at all time points (P < 0.01 for all). (4) The latency to escape platform in control group (51.75 +/- 11.27s) was longer than that in trial group (40.32 +/- 11.48s) and the sham operation group (36.58 +/- 10.83s) (P < 0.05); the frequency of passing through the platform in control group (2.34 +/- 2.42) was less than that in trial group (5.08 +/- 3.86) and the sham operation group (7.03 +/- 3.62) (P < 0.05). There was no significant difference between the trial group and the sham operation group (P > 0.05).

CONCLUSIONS(1) The expression of nestin and GAP-43 increased in hippocampal CA1 region of neonatal rats with HIBD, it may be involved in the activation of neural stem cells and the regeneration of neurocytes after HIBD. (2) The treatment with bFGF can improve the ability of learning and memory of neonatal rats with HIBD. (3) Exogenous bFGF could enhance the expression of nestin and GAP-43 in the brain of neonatal rats with HIBD, which may play an important role in restoration of neurons damaged due to hypoxia-ischemia.

Animals ; Animals, Newborn ; Brain ; drug effects ; pathology ; CA1 Region, Hippocampal ; pathology ; Fibroblast Growth Factor 2 ; therapeutic use ; GAP-43 Protein ; therapeutic use ; Hippocampus ; drug effects ; Hypoxia, Brain ; prevention & control ; Hypoxia-Ischemia, Brain ; prevention & control ; Intermediate Filament Proteins ; metabolism ; Ischemia ; prevention & control ; Maze Learning ; drug effects ; Nerve Tissue Proteins ; metabolism ; Nestin ; Neurons ; drug effects ; physiology ; Rats ; Rats, Wistar

OBJECTIVETo investigate the effect of Bcl-2 overexpression on Fas and TNFR1-mediated apoptosis and its possible mechanism in rat hippocampus following global ischemia/reperfusion (IR).

METHODSNinety healthy male SD rats were randomly divided into sham operated group, IR group and Bcl-2 overexpression group (BT group). Rat model of global IR was established by the 4-V0 method. The expressions of Bcl-2, Fas and TNFR1 and the cell apoptosis in the CA1 and CA3 regions were examined by HE staining, immunohistochemistry and TUNEL method.

RESULTSIn IR group, the neurons in the CA1 region showed an obvious reduction in number with disordered arrangement and interstitial edema 48 h after global IR. Such changes were not obvious in BT group. Immunohistochemistry showed that Fas expression in the CA1 region reached the peak level at 6 h in IR group with a greater expression intensity than that in BT group (P<0.05). TNFR1 was expressed at a higher level in IR group than in BT group (P<0.05), reaching the peak level at 24 h. In the sham group, the expression of Fas and TNFR1 was not detected the in CA1 and CA3 regions. Global IR caused increased cell apoptosis in the CA1 and CA3 regions, starting at 6 h and reached peak at 24 to 48 h. The cell apoptosis was less obvious in BT group (P<0.05).

CONCLUSIONFas and TNFR1 are expressed in the CA1 and CA3 regions after global IR in rats, suggesting the involvement of death receptor in cerebral IR injury. Bcl-2 overexpression decreases the expression of Fas and TNFR1 and cell apoptosis after global IR, thus offering protective effect against cerebral IR injury.

Animals ; Apoptosis ; Brain Ischemia ; metabolism ; physiopathology ; Hippocampus ; metabolism ; pathology ; Male ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Tumor Necrosis Factor, Type I ; metabolism ; Reperfusion Injury ; metabolism ; pathology ; prevention & control ; fas Receptor ; metabolism

OBJECTIVETo explore the possible mechanism of electroacupuncture preconditioning (EAPC) and combined with ATP-sensitive potassium channel (KATP) blocker preconditioning for hypoxia/ischemic brain injury protection by observing the changes of the immediate genes (c-fos and c-jun protein content) in brain at the early stage after cerebral hypoxia/ischemic injury, and the effect of EAPC on these changes.

METHODSIntegrated density (ID) of c-fos and c-jun expression was measured by Western blot and computerized image processing.

RESULTSHypoxia/ischemia could induce c-fos and c-jun protein in both cerebral cortex and hippocampus simultaneously, with the peak appearing 2-4 hrs later, and the expression in hyppocampus was higher than that in cortex. EAPC could lower KATP blocker induced permanent high expression in hyppocampus.

CONCLUSIONThe effect of EAPC preconditioning in antagonizing cerebral hypoxia/ischemic injury may be related with its action in activating KATP, inhibiting the neuron apoptosis induced by the immediate genes at early stage of injury.

Animals ; Animals, Newborn ; Apoptosis ; Brain ; metabolism ; pathology ; Electroacupuncture ; Female ; Hypoxia-Ischemia, Brain ; metabolism ; prevention & control ; Ischemic Preconditioning ; methods ; Male ; Proto-Oncogene Proteins c-fos ; metabolism ; Proto-Oncogene Proteins c-jun ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Animals ; Apoptosis ; physiology ; Brain Ischemia ; enzymology ; physiopathology ; Caspase 3 ; metabolism ; Ischemic Postconditioning ; methods ; Male ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; enzymology ; pathology ; prevention & control