Although many agents for acute ischemic stroke treatment have been developed from extensive preclinical studies, most have failed in clinical trials. As a result, researchers are seeking other methods or agents based on previous studies. Among the various prospective approaches, vascular protection might be the key for development of therapeutic agents for stroke and for improvements in the efficacy and safety of conventional therapies. Traditional medicines in Asian countries are based on clinical experiences and literature accumulated over thousands of years. To date, many studies have used traditional herbal medicines to prove or develop new agents based on stroke treatments mentioned in traditional medicinal theory or other clinical data. In the current review, we describe the vascular factors related to ischemic brain damage and the herbal medicines that impact these factors, including Salviae Miltiorrhizae Radix, Notoginseng Radix, and Curcumae Rhizoma, based on scientific reports and traditional medical theory. Further, we point out the problems associated with herbal medicines in stroke research and propose better methodologies to address these problems.
Blood Vessels ; drug effects ; pathology ; Brain Edema ; drug therapy ; Brain Ischemia ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Humans ; Medicine, Traditional ; Stroke ; drug therapy

Brain edema leading to an expansion of brain volume has a crucial impact on morbidity and mortality following traumatic brain injury as it increases intracranial pressure, impairs cerebral perfusion and oxygenation, and contributes to additional ischemic injuries. Classically, two major types of traumatic brain edema exist: "vasogenic" and "cytotoxic/cellular". However, the cellular and molecular mechanisms contributing to the development/resolution of traumatic brain edema are poorly understood and no effective drugs can be used now. Aquaporin-4 (AQP4) is a water-channel protein expressed strongly in the brain, predominantly in astrocyte foot processes at the borders between the brain parenchyma and major fluid compartments, including cerebrospinal fluid and blood. This distribution suggests that AQP4 controls water fluxes into and out of the brain parenchyma. In cytotoxic edema, AQP4 deletion slows the rate of water entry into brain, whereas in vasogenic edema, AQP4 deletion reduces the rate of water outflow from brain parenchyma. AQP4 has been proposed as a novel drug target in brain edema. These findings suggest that modulation of AQP4 expression or function may be beneficial in traumatic brain edema.
Animals ; Aquaporin 4 ; analysis ; antagonists & inhibitors ; chemistry ; physiology ; Brain ; metabolism ; Brain Edema ; drug therapy ; etiology ; Brain Injuries ; complications ; Humans ; Mice

OBJECTIVE: To investigate the protective effect of edaravone and danshensu conjugate (IM-009) on focal cerebral ischemia-reperfusion injury in rats and its underlying mechanisms.
 METHODS: Rats were randomly assigned into 6 groups, including a sham group, a model group, an edaravone-treated group, a danshensu-treated group, a low dose of IM-009-treated group and a high dose of IM-009-treated group. The focal cerebral ischemia-reperfusion model was established by intraluminal filament. After the drug treatment, the infarct volume and extent of brain edema were measured. The levels of MDA and SOD were determined by the corresponding assay kit. The scavenging effect of IM-009 on hydroxyl radical and superoxide anion was also measured in a cell free system.
 RESULTS: 1) In comparison with the model group, the infarct volume and water content in rat brain after IM-009 treatment were significantly reduced. The protective effect of IM-009 at higher dose was much stronger than that of edaravone or danshensu (all P<0.05). 2) IM-009 significantly reduced the levels of MDA and increased the activity of SOD (all P<0.05). 3) IM-009 demonstrated strong activities in scavenging .OH and .O(2)(-) (all P<0.05).
 CONCLUSION IM-009 is able to protect rats from ischemia-reperfusion injury. The protective effect of IM-009 could be due to its radical-scavenging action.
Animals ; Antipyrine ; analogs & derivatives ; pharmacology ; Brain Edema ; Brain Ischemia ; drug therapy ; Cerebral Infarction ; drug therapy ; Edaravone ; Lactates ; pharmacology ; Malondialdehyde ; metabolism ; Rats ; Reperfusion Injury ; drug therapy ; Superoxide Dismutase ; metabolism

OBJECTIVETo explore the effects of Xingnaojing injection on cerebral edema and blood-brain barrier (BBB) in rats following traumatic brain injury (TBI).

METHODSA total of 108 adult male Sprague-Dawley rats were used as subjects and randomly assigned to three groups: sham-operation, TBI and Xingnaojing injection groups (10 ml/kg/d, intraperitoneal injection). TBI in rats was set up by the improved device of Feeney's weight-dropping model with the impact of 600 g.cm. Brain water content and BBB permeability expressed as Evans blue content were measured at 1, 3, 5 and 7 days after surgery.

RESULTSIn sham-operation group, brain water content and Evans blue content in brain tissue were 78.97%+/-1.22% and 5.13 microgram+/-0.71 microgram. Following TBI, water content in brain tissue was increased significantly at 1, 3, 5 and 7 days (83.49%+/-0.54%, 82.74%+/-0.72%, 80.22%+/-0.68%, 79.21%+/-0.60%), being significantly higher than that in sham operation group (P less than 0.05). Evans blue content was increased in TBI group (16.54 microgram+/-0.60 microgram, 14.92 microgram+/-0.71 microgram, 12.44 microgram+/-0.92 microgram, 10.14 microgram+/-0.52 microgram) as compared with sham-operation group(P less than 0.05). After treatment with Xingnaojing injection, brain water content decreased as compared with TBI group (81.91%+/-1.04%, 80.38%+/-0.72%, 79.54%+/-0.58%, 78.60%+/-0.77%, P less than 0.05). Xingnaojing injection also reduced the leakage of BBB as compared with TBI group (15.11 microgram+/-0.63 microgram, 13.62 microgram+/-0.85 microgram, 10.06microgram+/-0.67 microgram, 9.54 microgram+/-0.41 microgram, P less than 0.05).

CONCLUSIONXingnaojing injection could alleviate cerebral edema following TBI via reducing permeability of BBB.

Animals ; Blood-Brain Barrier ; drug effects ; Brain ; pathology ; Brain Edema ; drug therapy ; Brain Injuries ; drug therapy ; pathology ; Drugs, Chinese Herbal ; administration & dosage ; Injections ; Male ; Medicine, Chinese Traditional ; Permeability ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the neuro-protective effect of Xuesaitong Injection (XST) on brain inflammatory response after transient focal cerebral ischemia/reperfusion in rats.

METHODSFocal cerebral ischemia/reperfusion models of male rats were induced by transient occlusion for 2 h of middle cerebral artery (MCA) which was followed by 24 h reperfusion. XST was administered through intraperitoneal injection of 25 mg/kg or 50 mg/kg at 4 h after the onset of ischemia. After reperfusion for 24 h, the neurological function score was evaluated, the brain edema was detected with dry-wet weight method, the myeloperoxidase (MPO) activity and the expression of intercellular adhesion molecule-1 (ICAM-1) of ischemic cerebral cortex and caudate putamen was determined by spectrophotometry and immunohistochemistry respectively.

RESULTSXST not only lowered neurological function score at the dose of 50 mg/kg, but reduced brain edema and inhibited MPO activity and ICAM-1 expression as compared with the ischemia/reperfusion model group (P < 0.01).

CONCLUSIONXST has a definite effect on inhibiting the expression of ICAM-1 and neutrophil infiltration in rats with cerebral ischemia/reperfusion when treatment started at 4 h after ischemia onset, and also attenuates inflammation in the infarcted cerebral area.

Animals ; Brain Edema ; drug therapy ; immunology ; Brain Ischemia ; drug therapy ; immunology ; Encephalitis ; drug therapy ; immunology ; Intercellular Adhesion Molecule-1 ; metabolism ; Male ; Neuroprotective Agents ; pharmacology ; Neutrophils ; immunology ; Peroxidase ; metabolism ; Rats ; Rats, Wistar ; Reperfusion Injury ; drug therapy ; immunology ; Saponins ; pharmacology

Adult ; Aged ; Bevacizumab ; therapeutic use ; Brain Neoplasms ; drug therapy ; therapy ; Edema ; drug therapy ; etiology ; Female ; Humans ; Male ; Middle Aged ; Re-Irradiation ; adverse effects

Our study was designed to determine whether methylprednisolone exerts a beneficial effect after experimental moderate diffuse brain injury and whether this possible beneficial effect is affected by the dosage, the timing of administration, and the methods of treatment. A total of 200 anesthetized adult rats were injured utilizing a weight-drop device through a Plexiglas guide tube. These rats were divided into eight groups: Group 1 (n=35) was assigned to receive no methylprednisolone after impact (control group), Group 2 (n=25) received an initial intraperitoneal administration of methylprednisolone with a dose of 5 mg/kg at 1hour after cranial impact, followed by administration with a maintenance dose of 5 mg/kg/4 hours. Group 3 (n=25), group 5 (n=25), and group 7 (n=20) received an initial 30 mg/kg at 1 hour, 4 hours, and 8 hours, respectively without a maintenance dose. Group 4 (n=25), group 6 (n=25), and group 8 (n=20) received an initial 30 mg/kg at 1 hour, 4 hours, and 8 hours after impact, with a maintenance dose of 15 mg/kg/4 hours. Measured water content of brain tissue expressed the amount of water as the difference between fresh and dry weight. At 48 hours after impact, the water content in group 4 and 6 were significantly lower than group 1. Mean SD was 61.4 0.37% in group 4 (p<0.03), 61.5 0.34% in group 6 (p<0.001), and 63.6 0.48% in group 1. Compared to group 1, the difference was not statistically significant in group 2 (p>0.1), group 3 (p>0.5), group 5 (p>0.6), group 7 (p>0.1), and group 8 (p>0.5). Groups treated with mega dose before 4hours after head injury, including maintenance dose, showed beneficial effects. Our study suggests that the efficacy of methylprednisolone in head injury was related to the dosage, the timing of administration, and method of treatment.
Animal ; Brain Edema/prevention | control* ; Brain Injuries/drug therapy* ; Dose-Response Relationship, Drug ; Injections, Intraperitoneal ; Methylprednisolone/therapeutic use* ; Neuroprotective Agents/therapeutic use* ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: The authors analyze the clinical characteristics of the long-term survivors and elucidate the biological factors responsible for long-term survival. METHODS: The 166 cases of histologically confirmed glioblastoma from Jan 1983 to Aug 1999 were included. Medical records and radiological findings were reviewed to analyze age, performance status, location and number of the tumor, the amount of peri-tumoral edema, the extent of surgical resection and history of radiation and/or chemotherapy. The overall survival was 13.6 months and the 1-year survival rate was 59%. The thirteen patients(6.9%), lived more than three years after diagnosis, defined as the long-term survivors. RESULTS: Performance status(KPS>or=70), number of masses(single with no CSF seeding), and hemispheric location(not involving basal ganglia and/or brain stem) showed favorable influence on the patient survival in univariate analysis. Also post-operative radiation and chemotherapy resulted in significant improvement of the survival. However, in multivariate analysis, age(under 40 years) was the most significant prognostic factor. All the other factors which was significant in univariate analysis except the location of the tumor, also verified as significant prognostic factors in multivariate analysis. The long-term survivors had at least more than five out of seven significant prognostic factors in multivariate analysis. And these factors occurred more frequently and showed significances in the long-term survivors than the other patient group except the debulking surgery. CONCLUSION: The age at the diagnosis and invasiveness resulted in multiple tumor and/or CSF seeding were the most significant prognostic factors.
Basal Ganglia ; Biological Factors ; Brain ; Diagnosis ; Drug Therapy ; Edema ; Glioblastoma* ; Humans ; Medical Records ; Multivariate Analysis ; Survival Rate ; Survivors*

Glioma-related edema (GRE) is a significant contributor to morbidity and mortality from glioma. GRE is a complicated process involving not only peritumoral edema but also the water content of the tumor body. In terms of etiology, this condition derives from both GRE in the untreated state and GRE secondary to clinical intervention, and different cell types contribute to distinct components of GRE. Peritumoral edema was previously believed to loosen glioma tissue, facilitating tumor-cell invasion; however, the nutrition hypothesis of the tumor microecosystem suggests that tumor cells invade for the sake of nutrition. Edema is the pathologic consequence of the reconstructed trophic linkage within the tumor microecosystem. Glioma cells induce peritumoral brain edema via an active process that supplies a suitable niche for peritumoral invasive cells, suggesting that glioma-related peritumoral brain edema is determined by the invasive property of tumor cells. There are differences between pivotal molecular events and reactive molecular events in the development of GRE. Molecular therapy should target the former, as targeting reactive molecular events will produce undesired or even adverse results. At present, brain glioma angiogenesis models have not been translated into a new understanding of the features of brain images. The effect of these models on peritumoral brain edema is unclear. Clinical approaches should be transformed on the basis of new knowledge of the molecular mechanism underlying GRE. Exploring clinical assessment methods, optimizing the existing control strategy of GRE, and simultaneously developing new treatments are essential.
Brain Edema ; diagnosis ; drug therapy ; metabolism ; pathology ; Brain Neoplasms ; diagnosis ; drug therapy ; metabolism ; pathology ; Glioma ; diagnosis ; drug therapy ; metabolism ; pathology ; Humans ; Magnetic Resonance Imaging ; Molecular Targeted Therapy ; Vascular Endothelial Growth Factor A ; metabolism

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