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 investigate the effects of propofol, midazolam and thiopental sodium on outcomes and amino acid accumulation in focal cerebral ischemia-reperfusion in rats.

METHODSMale Sprague Dawley (SD) rats were scheduled to undergo 3-hour middle cerebral artery occlusion by intraluminal suture and 24-hour reperfusion. Neurologic outcomes were scored on a 0-5 grading scale. Infarct volume was shown with triphenyltetrazolium chloride staining and measured by an image analysis system. Concentrations of various amino acids (aspartate, glutamate, glycine, taurine, and gama-aminobutyric acid) were measured after 3 hours of reperfusion using high performance liquid chromatography. Propofol, midazolam and thiopental sodium were given intraperitoneally at the beginning of reperfusion.

RESULTSBoth propofol and midazolam attenuated neurological deficits and reduced infarct and edema volumes. Propofol showed better neurological protection than midazolam while thiopental sodium did not exhibit any protective effect. Both propofol and midazolam decreased excitatory amino acids accumulation, while propofol increased gama-aminobutyric acid accumulation in ischemic areas in reperfusion.

CONCLUSIONPropofol and midazolam, but not thiopental sodium, may provide protective effects against reperfusion induced injury in rats subjected to focal cerebral ischemia. This neurological protection may be due to the acceleration of excitatory amino acids elimination in reperfusion.

Adenosine Triphosphate ; metabolism ; Animals ; Brain ; metabolism ; Brain Edema ; drug therapy ; Brain Ischemia ; metabolism ; Excitatory Amino Acids ; metabolism ; Male ; Midazolam ; pharmacology ; Myocardial Infarction ; drug therapy ; Neuroprotective Agents ; pharmacology ; Propofol ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; prevention & control ; Thiopental ; pharmacology

This study was done to determine the neuroprotective effect of cycloheximide on neonatal hypoxic-ischemic brain injury. Seven day-old newborn rat pups were subjected to 90 min of 8% oxygen following a unilateral carotid artery ligation. The extent of cerebral infarction was evaluated at 1 and 4 week of recovery. Apoptosis was identified by performing terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining and flow cytometry with a combination of fluoresceinated annexin V and propidium iodide. Brain infarction area was significantly increased at 4 week compared to 1 week after hypoxia-ischemia in the control group. With cycloheximide treatment, the number of TUNEL positive cells in the ipsilateral cerebral cortex at 48 hr and peri-infarct area at 1 and 4 week of recovery was significantly reduced, both apoptotic and necrotic cells by flow cytometry 48 hr after the injury were significantly reduced, and the extent of cerebral infarction at 1 and 4 week of recovery was also significantly attenuated compared to the hypoxia-ischemia control group. In summary, our data suggest that apoptosis plays an important role in the development of delayed infarction, and inhibition of apoptosis with cycloheximide significantly reduces the ensuing cerebral infarction in a newborn rat pup model of cerebral hypoxia-ischemia.
Time Factors ; Rats, Sprague-Dawley ; Rats ; Propidium ; Neuroprotective Agents/*pharmacology ; In Situ Nick-End Labeling ; Hypoxia-Ischemia, Brain/*drug therapy/metabolism/pathology ; Cycloheximide/*pharmacology ; Brain Infarction/pathology/prevention & control ; Apoptosis/drug effects ; Annexin A5/metabolism ; Animals, Newborn ; Animals

OBJECTIVETo evaluate the preventive and therapeutic effect of thymosin alpha(1) on lung infections in critical patients with tracheotomy.

METHODSForty-two patients were randomly divided into treatment group and control group to receive daily subcutaneous thymosin injection at 11.6 mg and saline of 2 ml for 7 days, respectively.

RESULTSCompared with the control group, the infection rate, white blood cell count, C-reactive protein, tumor necrosis factor-alpha and interleukiu-6 were significantly lower in the treatment group.

CONCLUSIONThymosin alpha(1) can be effective for prevention and treatment of lung infections in critical patients with tracheotomy and may improve the patients' immunity and prognosis.

Adjuvants, Immunologic ; therapeutic use ; Adolescent ; Adult ; Aged ; Brain Injuries ; drug therapy ; surgery ; Cerebral Infarction ; drug therapy ; Critical Illness ; Female ; Humans ; Intensive Care Units ; Male ; Middle Aged ; Pneumonia ; prevention & control ; Thymosin ; analogs & derivatives ; therapeutic use ; Tracheotomy ; adverse effects

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 explore the neuroprotective effect of vasoactive intestinal peptide (VIP) in rat ischemic brain injury.

METHODSVIP was administered via intracerebroventricular injection in SD rats prior to focal cerebral ischemia by intraluminal occlusion of the middle cerebral artery. The infarct volume was assessed with TTC staining, and immunohistochemistry was performed to analyze the S100beta expression in the cerebral tissue, with the serum concentrations of S100beta detected by double-antibody sandwich enzyme-linked immunosorbent assay.

RESULTSAfter VIP injection, the relative infarct volume in the rats with cerebral ischemia was significantly reduced by 32.3% as compared with the volume in the control group on day 1 (P<0.05), and the number of S100beta-positive cells was significantly decreased in the cerebral tissue (P<0.05). The injection also resulted in significantly decreased serum S100beta concentrations in the rats (P<0.05).

CONCLUSIONVIP injection can reduce the infarct volume in rats with focal cerebral ischemia, suggesting the neuroprotective effect of VIP in brain ischemia possibly by reducing S100beta overexpression.

Animals ; Brain Ischemia ; drug therapy ; Cerebral Infarction ; prevention & control ; Nerve Growth Factors ; blood ; Neuroprotective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; S100 Calcium Binding Protein beta Subunit ; S100 Proteins ; blood ; Vasoactive Intestinal Peptide ; pharmacology

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 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

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

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