Recent clinical trials have reported that methylprednisolone sodium succinate administered within 8 hours improves neurological recovery in human spinal cord injury (SCI). Methylprednisolone, however, was ineffective and possibly even deleterious when given more than 8 hours after injury. This finding suggests that a therapeutic time window exists in spinal cord injury. In order to determine the doses, durations and timing of methylprednisolone treatment for optimal neuroprotection, a single or two bolus dose of methylprednisolone (30 mg/kg) was administered at 10, 30, 120, 150 and 240 min. after three graded spinal cord injury. The primary outcome measure was 24-hour spinal cord lesion volumes estimated from spinal cord Na+ and K+ shifts. A single 30 mg/kg dose of methylprednisolone at 10 min. after injury significantly reduced 24-hour lesion volumes in injured rat spinal cords. However, any other methylprednisolone treatment starting 30 min. or more after injury had no effect on 24-hour lesion volumes compared to the vehicle control group. Moreover, delayed treatment increased lesion volumes in some cases. These results suggest that the NYU SCI model has a very short therapeutic window.
Animal ; Drug Administration Schedule ; Male ; Methylprednisolone Hemisuccinate/therapeutic use ; Methylprednisolone Hemisuccinate/administration & dosage* ; Neuroprotective Agents/therapeutic use ; Neuroprotective Agents/administration & dosage* ; Rats ; Rats, Long-Evans ; Spinal Cord/pathology ; Spinal Cord Injuries/pathology ; Spinal Cord Injuries/drug therapy*

Bronchopulmonary Dysplasia ; prevention & control ; Continuous Positive Airway Pressure ; Humans ; Infant, Newborn ; Neuroprotective Agents ; pharmacology ; Nitric Oxide ; administration & dosage ; Pulmonary Surfactants ; administration & dosage ; Respiratory Distress Syndrome, Newborn ; therapy

Survival rates after cardiac arrest have not changed substantially over the past 5 decades. Postcardiac arrest (CA) syndrome (PCAS) is the primary reason for the high mortality rate after successful restoration of spontaneous circulation (ROSC). Intravenous administration of Shenfu Injection (, SFI) may attenuate post-CA myocardial dysfunction and cerebral injury, inhibit systemic ischemia/reperfusion responses, and treat underlying diseases. In this article, we reviewed the therapeutic effects of SFI in PCAS. SFI might be useful in the treatment of PCAS, incorporating the multi-link and multi-target advantages of Chinese medicine into PCAS management. Further experimental and clinical research to verify the therapeutic effects of SFI in PCAS is required.
Cardiotonic Agents ; pharmacology ; therapeutic use ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Heart Arrest ; drug therapy ; physiopathology ; Humans ; Injections ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Syndrome

OBJECTIVETo investigate whether the protective effect of therapy with different combined neuroprotectant agents was better than that of single agent on focal cerebral ischemia.

METHODSThe right middle cerebral artery in the rats was occluded with suture occlusion technique. The rats were divided into five groups treated with FDP (50 mg/kg, n = 10), MK-801 (1 mg/kg, n = 10) and NAC (150 mg/kg, n = 10) singly, or in combination, respectively, by intraperitoneal infusion 30 minutes after vessel occlusion. The rats were weighed and assessed neurologically, based on a 5-point scale, six and 24 hours after focal cerebral ischemia. The expression of anti-apoptotic protein bcl-2 was observed with SDS-PAGE protein electrophoresis and Western blot technique.

RESULTThe optical density of bcl-2 increased more distinctly in the rats treated with combined neuroprotective agents than that with any single agent six and 24 hours after cerebral ischemia, with a statistically significant difference (P < 0.05).

CONCLUSIONSTreatment with combined neuroprotectant agents could un-regulate the anti-apoptotic protein bcl-2 more distinctly than that with any single agents. Combined use of neuroprotectants might be more effective than that of single agent in protecting rats' brain from ischemia.

Acetylcysteine ; administration & dosage ; Actins ; analysis ; Animals ; Brain Ischemia ; drug therapy ; metabolism ; Dizocilpine Maleate ; administration & dosage ; Drug Therapy, Combination ; Fructosediphosphates ; administration & dosage ; Male ; Molecular Weight ; Neuroprotective Agents ; administration & dosage ; Proto-Oncogene Proteins c-bcl-2 ; analysis ; Rats ; Rats, Wistar

OBJECTIVE: We investigated the neuroprotective effect of anthocyanin, oxygen radical scavenger extracted from raspberries, after traumatic spinal cord injury (SCI) in rats. METHODS: The animals were divided into two groups : the vehicle-treated group (control group, n=20) received an oral administration of normal saline via stomach intubation immediately after SCI, and the anthocyanin-treated group (AT group, n=20) received 400 mg/kg of cyanidin 3-O-beta-glucoside (C3G) in the same way. We compared the neurological functions, superoxide expressions and lesion volumes in two groups. RESULTS: At 14 days after SCI, the AT group showed significant improvement of the BBB score by 16.7+/-3.4%, platform hang by 40.0+/-9.1% and hind foot bar grab by 30.8+/-8.4% (p<0.05 in all outcomes). The degree of superoxide expression, represented by the ratio of red fluorescence intensity, was significantly lower in the AT group (0.98+/-0.38) than the control group (1.34+/-0.24) (p<0.05). The lesion volume in lesion periphery was 32.1+/-2.4 microL in the control and 24.5+/-2.3 microL in the AT group, respectively (p<0.05), and the motor neuron cell number of the anterior horn in lesion periphery was 8.3+/-5.1 cells/HPF in the control and 13.4+/-6.3 cells/HPF in the AT group, respectively (p<0.05). CONCLUSION: Anthocyanin seemed to reduce lesion volume and neuronal loss by its antioxidant effect and these resulted in improved functional recovery.
Administration, Oral ; Animals ; Anthocyanins ; Antioxidants ; Cell Count ; Fluorescence ; Foot ; Horns ; Intubation ; Motor Neurons ; Neurons ; Neuroprotective Agents ; Oxygen ; Spinal Cord ; Spinal Cord Injuries ; Stomach ; Superoxides

OBJECTIVETo investigate the neuroprotective effect, effective dose and time window of ginseng total saponins (GTS) treatment in rat after traumatic brain injury (TBI).

METHODSThe modified Feeney's method was used to establish TBI model in rat. GTS was treated intraperitoneally. The neurological function and histological morphology of brain tissue were observed.

RESULTSDifferent doses of GTS were used 6 h after TBI. The neurological and histological results showed that: compared with the TBI group, significant efficacy was observed 2 - 14 days after injury with GTS treatment at 10, 20, 40, 60 and 80 mg/kg (P < 0.05); The effects of GTS at 20, 40, and 60 mg/kg were better than those of GTS at 10 and 80 mg/kg. During the research on the time window of GTS intervention, GTS (20 mg/kg) showed significant effect when used at 3 h and 6 h after TBI; however 12 h, 24 h after TBI, application of GTS did not exert any significant effect.

CONCLUSIONGTS intervention after TBI could reduce brain damage and promote recovery of the neurological function. Among doses of GTS 5 - 80 mg/kg, 20 - 60 mg/kg is the best dose limit. The effective time window of GTS is 6 h after TBI.

Animals ; Brain Injuries ; drug therapy ; Male ; Neuroprotective Agents ; Panax ; chemistry ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Saponins ; administration & dosage ; therapeutic use ; Time Factors ; Treatment Outcome

Vascular endothelial growth factor (VEGF) has been found to be the most powerful angiogenic factor. Studies have shown that cerebral ischemia and hypoxia stimulate the expressions of VEGF and its receptors in the brain, while exogenous VEGF promotes the formation of new blood vessels in the ischemic brain penumbra, and reduce the volume of cerebral infarction. The effect of VEGF on cerebral ischemia was previously explained the mechanism that VEGF had a specific mitogenetic roles in cerebral endothelial cells and thus promoted neovascularization; however recent evidence has shown that VEGF also has direct effects on neural and glial cells. Its multiple protection roles on central nervous system involve vascularization, neurogenesis, direct neurotrophic and neuroprotective effect, as well as antiapoptosis effect, especially when brain ischemia occurs. Further elucidation of these mechanisms on central nervous system may serve as a key procedure in understanding the main aspects of neural repair and neural protection, and develop effective therapeutic measures for intervention in stroke.
Animals ; Brain Ischemia ; drug therapy ; physiopathology ; Dose-Response Relationship, Drug ; Neovascularization, Physiologic ; drug effects ; Nerve Regeneration ; drug effects ; Neuroprotective Agents ; pharmacology ; Vascular Endothelial Growth Factor A ; administration & dosage ; pharmacology

Animals ; Animals, Newborn ; Antioxidants ; administration & dosage ; pharmacology ; Apoptosis ; drug effects ; Brain ; drug effects ; pathology ; Disease Models, Animal ; Female ; Hypoxia-Ischemia, Brain ; drug therapy ; metabolism ; pathology ; Immunohistochemistry ; Male ; Melatonin ; administration & dosage ; pharmacology ; Neuroprotective Agents ; administration & dosage ; pharmacology ; Rats ; Rats, Sprague-Dawley

To prepare rivastigmine liposome, rivastigmine was loaded into liposome via ammonium sulfate gradient method. Its pharmacokinetic profile in rats was evaluated after intranasal administration. The size, zeta potential, entrapped efficiency and release of rivastigmine from the liposome in vitro were determined. Plasma concentration of rivastigmine was determined by high performance liquid chromatography-tandem mass spectrometry (HPLC/MS) using antipyrine as internal standard. The pharmacokinetic parameters were calculated by DAS 2.0. The entrapped efficiency of rivastigmine liposome was (33.41 +/- 6.58) %, with the mean diameter of 154-236 nm and zeta potential of (-10.47 +/- 2.41) mV. The release behavior of rivastigmine was fitting the first order equation in vitro. The pharmacokinetic studies indicated that the C(max), T(max) and AUC(0-infinity), of rivastigmine liposome were (1.50 +/- 0.15) mg x L(-1), 15 min and (89.06 +/- 8.30) mg x L(-') x min, respectively. Rivastimine liposome was absorbed rapidly, and could reach a certain concentration in rat plasma after intranasal delivery.
Administration, Intranasal ; Animals ; Area Under Curve ; Chromatography, Liquid ; Drug Carriers ; Drug Compounding ; Liposomes ; Male ; Neuroprotective Agents ; administration & dosage ; blood ; chemistry ; pharmacokinetics ; Particle Size ; Phenylcarbamates ; administration & dosage ; blood ; chemistry ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Rivastigmine ; Tandem Mass Spectrometry

OBJECTIVETo observe the antidepressant effect of piperine and its neuroprotective mechanism.

METHODThe behavioral studies were performed in forced swimming test (FST) and tail suspension test (TST). To further explore the mechanisms underlying their antidepressant-like activities, CORT-induced neuroblastoma SH-SY5Y cells and isolated and cultured neural progenitor cells. By using MTT assay, the effect of piperine on neural cells proliferation was observed.

RESULTThe research results indicated that after a week of administration, piperine (10, 20 mg x kg(-1)) could significantly reduce the duration of immobility in both FST and TST. Piperine has the protective effect on neuroblastoma cells and increased proliferation of hippocampus neural progenitor cells.

CONCLUSIONIn the present study, we demonstrated that the antidepressant-like effects of piperine and its mechanisms might be involved by up-regulation of the progenitor cell proliferation of hippocampus and cytoprotective activity.

Alkaloids ; administration & dosage ; Animals ; Antidepressive Agents ; administration & dosage ; Benzodioxoles ; administration & dosage ; Cell Line ; Cell Proliferation ; drug effects ; Cells, Cultured ; Female ; Mice ; Motor Activity ; drug effects ; Neurons ; cytology ; drug effects ; Neuroprotective Agents ; administration & dosage ; Piperidines ; administration & dosage ; Polyunsaturated Alkamides ; administration & dosage ; Random Allocation ; Stem Cells ; cytology ; drug effects