OBJECTIVE: To investigate whether rapamycin treatment starting at 24 h after cerebral ischemia/reperfusion(I/R) has protective effect on brain injury in rats. METHODS: The rat I/R model was established by middle cerebral artery occlusion according to Longa's method. A total of 104 Sprague Dawley rats were randomly divided into sham group, model group, and rapamycin-treated groups (6 h or 24 h after modeling). Neurological function was assessed with neurological severity score (NSS). Triphenyl tetrazolium chloride (TTC) staining and Fluoro-Jade B (FJB) staining were used to examine the infarct volume and neuronal apoptosis, respectively. The expression of p-S6 protein in mTOR signaling pathway was detected by Western blot analysis. RESULTS: Compared with sham group, NSS of the model group was significantly increased and TTC staining indicated obvious infarct area (all <0.01). Furthermore, significantly increased number of FJB-positive cells and p-S6 expression in the penumbra area were shown in the model group (all <0.01). Compared with the model group, both rapamycin-treated groups demonstrated decreased NSS, infarction volume and FJB positive cells as well as p-S6 expression in the penumbra area (<0.05 or <0.01). There was no significant difference between the groups of rapamycin administrated 6 h and 24 h after modeling (all >0.05). CONCLUSIONS Rapamycin treatment starting at 24 h after I/R exhibits protective effect on brain injury in rats.
Animals ; Brain Ischemia ; drug therapy ; Immunosuppressive Agents ; therapeutic use ; Infarction, Middle Cerebral Artery ; drug therapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; prevention & control ; Sirolimus ; therapeutic use ; Treatment Outcome

OBJECTIVETo tentatively establish a diagnosis and treatment mode for effectively controlling the progress of cerebral microlesions (CM) and preventing the incidence of cerebral infarction (CI) by comparing different intervention modes for treating CM.

METHODSUsing a prospective, nonrandomized, controlled trial, 408 subjects with multiple CM were assigned to the Chinese medical pharmacy intervention group (Group A, 100 case), the aspirin intervention group (Group B, 104 cases), the negative control group (Group C, 100 cases), and the non-intervention group (Group D, 104 cases). No intervention was given to those in Group D. Patients in the other 3 groups were intervened by life style and routine therapies of vasculogenic risk factors. Those in Group A took Guizhi Fuling Pill (GFP) and earthworm powder additionally. Those in Group B took aspirin additionally. They were routinely followed-up. The CM, the changes of vasculogenic risk factors, and the incidence rate of CI were compared among the 4 groups.

RESULTSThe total effective rate of CM was 66.67% in Group A, obviously higher than that of Group B (52.32%), Group C (42.86%), and Group D (37.04%), respectively. It was obviously higher in Group B than in Group D, showing statistical difference (P <0.01, P <0.05). After treatment, the serum levels of LDL-C, TC, and TG were obviously lower in Group A than in Group B (P <0.05); the serum levels of LDL-C and TC were obviously lower in Group A than in Group C (P <0.01); the systolic pressure was obviously lower in Group A than in Group D (P <0.05). The systolic pressure and the serum TC level were obviously lower in Group C than in Group D (P <0.05). The incidence rate of CI was 2.17% (2/92 cases) in Group A, obviously lower than that of Group C (11.36% ,10/88 cases) and Group D (14.44%, 13/90 cases), showing statistical difference (P <0.05). But there was no statistical difference between Group A and Group B (6.74% ,6/89 cases) (P >0.05).

CONCLUSIONSGFP combined earthworm powder could treat CM, control vasculogenic risk factors, and finally prevent the incidence of CI. Standard Chinese medical intervention mode showed the optimal effects in treating CM and preventing the incidence of CI, and perhaps it could be spread clinically.

Adult ; Aged ; Aged, 80 and over ; Aspirin ; therapeutic use ; Brain ; pathology ; Cerebral Infarction ; drug therapy ; pathology ; prevention & control ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Phytotherapy ; Prospective Studies ; Risk Factors ; Treatment Outcome

OBJECTIVETo investigate the effects of caffeic acid ester fraction (Caf) from Erigeron breviscapus, mainly composed of dicaffeoylquinic acids (diCQAs), on microglial activation in vitro and focal cerebral ischemia in vivo.

METHODSThe production of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin-1β (IL-1β) induced by lipopolysaccharide (LPS) treatment in rat primary cultured microglia were measured by Griess reaction or enzyme-linked immunosorbent assay. Cell viability of cortical neurons was measured using AlamarBlue reagent. The behavioral tests and the infarct area of brain were used to evaluate the damage to central nervous system in rat middle cerebral artery occlusion (MCAO) model of cerebral ischemia. Real time polymerase chain reaction was used to determine the expression of inducible nitric oxide synthase (iNOS), TNF-α and IL-1β mRNA in ischemic cerebral tissues.

RESULTSCaf inhibited the production of NO, TNF-α and IL-1β induced by LPS treatment in primary microglia in a dose-dependent manner. Exposure of cortical neurons to conditioned medium from Caf-treated microglia increased neuronal cell viability (P<0.01) compared with conditioned medium from LPS-treated alone. In MCAO rat model of cerebral ischemia, Caf could significantly improve neurobehavioural performance and reduce percentage infarct volume compared with the vehicle group (P<0.05). Caf could also significantly inhibit the up-regulation of iNOS, TNF-α, and IL-1β gene expressions in ischemic cerebral tissues.

CONCLUSIONCaf could suppress microglial activation, which may be one mechanism of its neuroprotective effect against ischemia.

Animals ; Brain ; drug effects ; metabolism ; pathology ; Brain Ischemia ; complications ; drug therapy ; pathology ; prevention & control ; Caffeic Acids ; chemistry ; pharmacology ; Chemical Fractionation ; Chromatography, High Pressure Liquid ; Erigeron ; chemistry ; Gene Expression Regulation ; drug effects ; Infarction, Middle Cerebral Artery ; complications ; pathology ; Interleukin-1beta ; genetics ; metabolism ; Microglia ; drug effects ; metabolism ; pathology ; Neuroprotective Agents ; chemistry ; pharmacology ; therapeutic use ; Nitric Oxide Synthase Type II ; genetics ; metabolism ; Plant Extracts ; pharmacology ; Quinic Acid ; analogs & derivatives ; chemistry ; pharmacology ; therapeutic use ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

A Dieulafoy lesion in the rectum is a very rare and it can cause massive lower gastrointestinal bleeding. An 83-year-old man visited our hospital. He had chronic constipation and had taken aspirin for about 10 years because of a previous brain infarction. He was admitted because of a recent brain stroke. On the third hospital day, he had massive hematochezia and suddenly developed hypovolemic shock. Abdominal computed tomography showed active arterial bleeding on the left side of the mid-rectum. Emergency sigmoidoscopy showed an exposed vessel with blood spurting from the rectal wall. The active bleeding was controlled successfully by an injection of epinephrine and two hemoclippings. On the fourth day after the procedure, he had massive recurrent hematochezia, and his vital signs were unstable. Doppler-guided hemorrhoidal artery band ligation was performed urgently at two sites. However, he rebled on the third postoperative day. Selective inferior mesenteric angiography revealed an arterial pseudoaneurysm in a branch of the superior rectal artery, as the cause of rectal bleeding, and this was embolized successfully. We report a rare case of life-threatening rectal bleeding caused by a Dieulafoy lesion combined with pseudoaneurysm of the superior rectal artery which was treated successfully with embolization.
Aged, 80 and over ; Aneurysm/radiography ; Angiography ; Aspirin/therapeutic use ; Brain Infarction/drug therapy/prevention & control ; Embolization, Therapeutic ; Gastrointestinal Hemorrhage/*diagnosis/etiology/therapy ; Hemorrhoids/*complications ; Humans ; Male ; Mesenteric Artery, Inferior/radiography ; Platelet Aggregation Inhibitors/therapeutic use ; Rectal Diseases/complications/diagnosis/therapy ; Rectum/blood supply ; Sigmoidoscopy ; Tomography, X-Ray Computed

A Dieulafoy lesion in the rectum is a very rare and it can cause massive lower gastrointestinal bleeding. An 83-year-old man visited our hospital. He had chronic constipation and had taken aspirin for about 10 years because of a previous brain infarction. He was admitted because of a recent brain stroke. On the third hospital day, he had massive hematochezia and suddenly developed hypovolemic shock. Abdominal computed tomography showed active arterial bleeding on the left side of the mid-rectum. Emergency sigmoidoscopy showed an exposed vessel with blood spurting from the rectal wall. The active bleeding was controlled successfully by an injection of epinephrine and two hemoclippings. On the fourth day after the procedure, he had massive recurrent hematochezia, and his vital signs were unstable. Doppler-guided hemorrhoidal artery band ligation was performed urgently at two sites. However, he rebled on the third postoperative day. Selective inferior mesenteric angiography revealed an arterial pseudoaneurysm in a branch of the superior rectal artery, as the cause of rectal bleeding, and this was embolized successfully. We report a rare case of life-threatening rectal bleeding caused by a Dieulafoy lesion combined with pseudoaneurysm of the superior rectal artery which was treated successfully with embolization.
Aged, 80 and over ; Aneurysm/radiography ; Angiography ; Aspirin/therapeutic use ; Brain Infarction/drug therapy/prevention & control ; Embolization, Therapeutic ; Gastrointestinal Hemorrhage/*diagnosis/etiology/therapy ; Hemorrhoids/*complications ; Humans ; Male ; Mesenteric Artery, Inferior/radiography ; Platelet Aggregation Inhibitors/therapeutic use ; Rectal Diseases/complications/diagnosis/therapy ; Rectum/blood supply ; Sigmoidoscopy ; Tomography, X-Ray Computed

OBJECTIVETo compare the safety of intravenous thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) in ischemic patients under the guidance of CT and multi-mode MRI.

METHODSThe clinical, laboratory, and radiologic data from 113 consecutive hyperacute ischemic patients who received intravenous rtPA therapy from June 2009 to October 2011 was retrospectively reviewed. The rate of hemorrhagic transformation (HT) and the clinical outcome between CT and multi-mode MRI was compared. Etiological subgroups were classified according to Chinese ischemic stroke subclassification (CISS).

RESULTSAmong 113 patients treated with intravenous rtPA, the mean age was 66 ±12 years, 74(65.5%) were man, the pretreatment National Institutes of Health Stroke Scale score (NIHSS) was 12.4 ±6.5, and time from symptom onset to therapy was 259.7 ±131.7 min. Postlytic radiological HT was found in 34 patients (30.1%). Symptomatic ICH occurred in 9 patients (8%). Logistic regression analysis suggested that multi-mode MRI was an independent predictor of reduced risk of HT.

CONCLUSIONThe risk of hemorrhagic complications is lower in patients receiving intravenous thrombolytic therapy with rtPA guided by multi-mode MRI than those guided by CT scan.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Brain Infarction ; drug therapy ; Cerebral Hemorrhage ; chemically induced ; prevention & control ; Female ; Humans ; Logistic Models ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Recombinant Proteins ; administration & dosage ; adverse effects ; therapeutic use ; Retrospective Studies ; Stroke ; drug therapy ; Thrombolytic Therapy ; adverse effects ; Tissue Plasminogen Activator ; administration & dosage ; adverse effects ; therapeutic use ; Tomography, X-Ray Computed ; Young Adult

OBJECTIVETo investigate the effect of piperphentonamine hydrochloride (PPTA) on cognitive deficits induced by ischemia-reperfusion and explore the possible mechanisms.

METHODSSD rats were randomly divided into sham-operated group, ischemia-reperfusion group (with saline injection), PPTA-treated groups (2.5, 5, 10 mg/kg) and edaravone-treated group (6 mg/kg). Cerebral ischemia-reperfusion injury was induced by middle cerebral artery occlusion, and the agents were administrated 1 h after ischemia. At 24 h after ischemia, step-through passive avoidance test was carried out, and 24 h later IL-1β, TNF-α, caspase-3 and HSP-70 mRNA expressions in the ischemic brain tissues were measured with RT-PCR.

RESULTSIn the step-through passive avoidance test, the rats in the ischemia-reperfusion group showed significantly shorter latency and more error times than those in the sham group, and these behavioral changes were improved significantly by treatments with PPTA and edaravone. Cerebral ischemia-reperfusion caused significantly increased expressions of IL-1β, TNF-α, caspase-3 and HSP-70 mRNA, and these changes were obviously reversed by PPTA, but not by edaravone.

CONCLUSIONSPPTA can reverse cognitive deficits induced by cerebral ischemia-reperfusion probably by decreasing the inflammatory responses and cell apoptosis in the brain, suggesting its potential as a new therapeutic agent for improving the cognitive function following cerebral ischemia-reperfusion.

3,4-Methylenedioxyamphetamine ; analogs & derivatives ; therapeutic use ; Animals ; Brain Ischemia ; drug therapy ; Cognition Disorders ; prevention & control ; Infarction, Middle Cerebral Artery ; drug therapy ; Male ; Neuroprotective Agents ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; drug therapy ; prevention & control

OBJECTIVETo observe the effect of tanshinone IIA (TS IIA) pretreatment on the expression of the inflammatory factor IL-1β and RelA mRNA in rats with focal cerebral ischemia.

METHODSA total of 100 adult male SD rats were randomly divided into 6 groups, namely the model, ischemic preconditioning (IPC), TSIIA preconditioning, TSIIA treatment, sham-operated, and blank control groups. In the former 4 groups, rat models of focal cerebral ischemia were established with corresponding treatments. The expressions of IL-1β and RelA mRNA in each group were detected using RT-PCR.

RESULTSAll the groups showed expressions of IL-1β and RelA mRNA with the exception of the blank control group. Compared to the model group, TSIIA preconditioning group, TSIIA treatment group, and IPC group all had significantly reduced expression of IL-1β and RelA mRNA (P < 0.05). The expressions were lower in IPC group than in TSIIA preconditioning group and TSIIA treatment group(P < 0.05), and no significant difference was found in the expressions between the latter two groups.

CONCLUSIONThe protective effect of pretreatment with TS IIA against cerebral ischemia is related to the reduction of IL-1β and RelA mRNA expressions.

Animals ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; therapeutic use ; Antioxidants ; pharmacology ; therapeutic use ; Brain Ischemia ; drug therapy ; metabolism ; Diterpenes, Abietane ; pharmacology ; therapeutic use ; Infarction, Middle Cerebral Artery ; drug therapy ; metabolism ; Interleukin-1beta ; genetics ; metabolism ; Male ; RNA, Messenger ; genetics ; metabolism ; Rats ; Reperfusion Injury ; prevention & control ; Transcription Factor RelA ; genetics ; metabolism

OBJECTIVE: To investigate whether the reactive oxygen species (ROS) and mitochondrial ATP-sensitive potassium (mitoKATP) channels were involved in delayed neuroprotection induced by sevoflurane on tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) levels. METHODS: Eighty-four male SD rats weighing 250 approximately 280 g, undergoing thread embolism of the right middle cerebral artery occlusion (MCAO) to cause focal ischemia for 2 h and then undergoing 24 h reperfusion, were randomly divided into 7 groups (n=12, each): a sham group(S), an ischemia-reperfusion group (I/R), a sevoflurane preconditioning group (Sevo), a 2-mercaptopropionylglycine (ROS scavenger)+sevoflurane group (MPG+Sevo), a 5-hydroxydecanoate (a mitoK(ATP) blocker) + sevoflurane group (5-HD+Sevo), an MPG group, and a 5-HD group. The protein level of TNF-alpha and IL-1beta in the cerebral issue was detected by enzyme linked immunosorbent assay (ELISA) and the expression of mRNA was measured by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Apoptosis index (AI), the protein level and the mRNA expression of TNF-alpha and IL-1beta were significantly higher in the I/R group than those of Group S. Pre-administration of sevoflurane could inhibit the increase of the protein level and the expression of mRNA of TNF-alpha, and IL-1beta and attenuate the cerebral damage induced by ischemia-reperfusion. Neuroprotection of sevoflurane preconditioning was abolished by MPG and 5-HD. However, MPG and 5-HD alone had no effect. CONCLUSION Sevoflurane can produce delayed protection against cerebral ischemia-reperfusion injury by down-regulating TNF-alpha, IL-1beta protein, and mRNA expression.
Animals ; Hypoxia-Ischemia, Brain ; complications ; drug therapy ; Infarction, Middle Cerebral Artery ; complications ; drug therapy ; Interleukin-1beta ; genetics ; metabolism ; Ischemic Preconditioning ; methods ; KATP Channels ; metabolism ; Male ; Methyl Ethers ; pharmacology ; therapeutic use ; Neuroprotective Agents ; pharmacology ; therapeutic use ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Reperfusion Injury ; etiology ; prevention & control ; Sevoflurane ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

PURPOSE: This study was undertaken to determine the neuroprotective effect of granulocyte stimulating factor (G-CSF) on neonatal hypoxic-ischemic brain injury. MATERIALS AND METHODS: Seven-day-old male newborn rat pups were subjected to 110 minutes of 8% oxygen following a unilateral carotid artery ligation. Apoptosis was identified by performing terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining and flow cytometry with a combination of fluorescinated annexin V and propidium iodide (PI) and JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide). The extent of cerebral infarction was evaluated at 2 weeks after recovery. RESULTS: With a single dose (50microgram/kg) of G-CSF treatment immediately after hypoxic-ischemic insult, hypoxia-ischemia induced increase in TUNEL-positive cells, annexinV+/PI- and JC-1 positive apoptotic cells in the ipsilateral cerebral cortex was significantly reduced at 24 hours, measured by flow cytometry, and the extent of cerebral infarction at 2 weeks after recovery was also significantly attenuated compared to the hypoxia-ischemia control group. CONCLUSION: Our data suggest that G-CSF is neuroprotective by inhibiting apoptosis, thereby reducing the ensuing cerebral infarction in a newborn rat pup model of cerebral hypoxia-ischemia (HI).
Animals ; Apoptosis/*drug effects ; Brain/pathology ; Cerebral Infarction/pathology/prevention & control ; Flow Cytometry ; Granulocyte Colony-Stimulating Factor/*pharmacology/therapeutic use ; Hypoxia-Ischemia, Brain/*drug therapy/pathology ; In Situ Nick-End Labeling ; Male ; Organ Size ; Protective Agents/*pharmacology/therapeutic use ; Rats ; Rats, Sprague-Dawley ; Weight Gain