Administration, Topical ; Female ; Humans ; Intracranial Aneurysm ; complications ; Middle Aged ; Papaverine ; administration & dosage ; Vasospasm, Intracranial ; complications ; drug therapy

OBJECTIVETo observe the improvement of acupuncture in cerebral vasospasm (CVS) after embolization of ruptured aneurysms.

METHODSSixty cases were randomly divided into two groups, an acupuncture-medication group and a conventional treatment group, 30 cases in each one. The cases of CVS in conventional treatment group were treated with Nimodipine. In acupuncture-medication group, on the basis of the treatment as conventional treatment group, Baihui (GV 20) and Fengchi (GB 20) were selected as the main acupoints in the treatment of CVS. The treatment lasted for 3 weeks. Hunt-Hess scale for the standard assessment was adopted to determine the severity of disease before and after treatment and compare the efficacy between two groups. The transcranial Doppler (TCD) was conducted on the 1st, 4th, 7th, 10th, 14th and 21st days successively after operation, and the average flow velocity of 3 pairs of vessels (ACA, MCA, and PCA) was recorded. CT perfusion (CTP) was taken to test cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) on the 1st, 7th, 14th and 21st days successively.

RESULTSThe improvement of Hunt-Hess scale in acupuncture-medication group was superior to that in conventional treatment group (P < 0.05). The analysis of variance (ANOVA) was adopted in the comparison of ACA, MCA, PCA, CBF, CBV and MTT between two groups. The results showed that the therapy in either group achieved the effect on CVS (all P < 0.05). But, the improvements in the above mentioned indices in acupuncture-medication group were superior to those in conventional treatment group (all P < 0.05).

CONCLUSIONAcupuncture at Baihui (GV 20) and Fengchi (GB 20) down-regulates the peak values or upregulates the valley values. It releases the peak of CVS effectively, improves the clinical prognosis significantly and is the effective therapy for CVS after subarachnoid hemorrhage.

Acupuncture Therapy ; Adult ; Aged ; Aneurysm, Ruptured ; complications ; surgery ; therapy ; Balloon Occlusion ; Female ; Humans ; Male ; Middle Aged ; Treatment Outcome ; Vasospasm, Intracranial ; etiology ; therapy

OBJECTIVE: The management of patients with ruptured cerebral aneurysms and severe vasospasm is subject to considerable controversy. We intended to describe herein an endovascular technique for the simultaneous treatment of aneurysms and vasospasm. MATERIALS AND METHODS: A series of 11 patients undergoing simultaneous endovascular treatment of ruptured aneurysms and vasospasm were reviewed. After placement of a guiding catheter within the proximal internal carotid artery for coil embolization, an infusion line of nimodipine was wired to one hub, and of a microcatheter was advanced through another hub (to select and deliver detachable coils). Nimodipine was then infused continuously during the coil embolization. RESULTS: This technique was applied to 11 ruptured aneurysms accompanied by vasospasm (anterior communicating artery, 6 patients; internal carotid artery, 2 patients; posterior communicating and middle cerebral arteries, 1 patient each). Aneurysmal occlusion by coils and nimodipine-induced angioplasty were simultaneously achieved, resulting in excellent outcomes for all patients, and there were no procedure-related complications. Eight patients required repeated nimodipine infusions. CONCLUSION: Our small series of patients suggests that the simultaneous endovascular management of ruptured cerebral aneurysms and vasospasm is a viable approach in patients presenting with subarachnoid hemorrhage and severe vasospasm.
Adult ; Aged ; Aneurysm, Ruptured/*therapy ; Carotid Artery, Internal/radiography ; Embolization, Therapeutic ; *Endovascular Procedures ; Female ; Humans ; Intracranial Aneurysm/*therapy ; Magnetic Resonance Angiography ; Male ; Middle Aged ; Nimodipine/therapeutic use ; Retrospective Studies ; Vasodilator Agents/therapeutic use ; Vasospasm, Intracranial/*therapy

OBJECTIVETo evaluate the effects of urinary kallidinogenase on subarachnoid hemorrhage (SAH) in rabbits.

METHODSRabbits symptomatic cerebral vasospasm model was built though Endo method, among the 40 rabbits, 8 died or had severe nervous system syndrome, the other 32 were randomly divided into 4 groups:group A, control group, injection of normal saline to the cisterna magna;group B, subarachnoid hemorrhage;group C, injection of human urinary tissue kallikreins;group D, treated with Nimodipine. The behavior scores, neurological scores and cerebral angiography changes were observed.

RESULTSFood intake obviously decreased and neurological deficit were seen in group B, while which were attenuated in group C and group D, and group A was normal. Comparing the diameter of basilar artery was (1.9 +/- 0.3) mm before SAH, the diameter of group B 4 d later was (1.5 +/- 0.3) mm, 7 d later (1.4 +/- 0.3) mm, the difference was significant (P < 0.05). Comparing with group C on the day 4th and 7th, the diameters of basilar artery were significantly different (P < 0.001). Comparing with group D on the day 4th, 7th and 14th, there was no obvious improvement.

CONCLUSIONUrinary kallidinogenase and Nimodipine can obviously alleviate symptomatic cerebral vasospasm in rabbits remarkably, but the former's effect of attenuating vasospasm is better than that of Nimodipine.

Animals ; Disease Models, Animal ; Female ; Humans ; Male ; Nimodipine ; therapeutic use ; Rabbits ; Random Allocation ; Tissue Kallikreins ; therapeutic use ; Vasodilator Agents ; therapeutic use ; Vasospasm, Intracranial ; drug therapy

OBJECTIVETo investigate the effects and possible mechanisms of puerarin on the vascular active factors correlated to cerebral vasospasm (CVS) after aneurysm subarachnoid hemorrhage (aSAH).

METHODSFifty-four patients with aSAH were randomly assigned to the puerarin group (30 cases) and the control group (24 cases) by lot. On the basis of routine treatment, the patients in the puerarin group were intravenously dripped with 0.5 g puerarin by adding in 250 mL glucose injection once daily. The injection was given starting from the 3rd day of the disease course, for 14 successive days. The plasma levels of nitric oxide (NO), endothelin-1 (ET-1), thromboxane B, (TXB2), 6-Keto-prostaglandin F1alpha (6-K-PGF1alpha) were compared between the two groups pre- and post-therapy. The incidence of cerebral vasospasm (CVS) was observed using transcranial Doppler (TCD). The Glasgow outcome scale (GOS) were compared at discharge between the two groups.

RESULTSCompared with the control group, the plasma levels of NO, ET-1, and 6-K-PGF1alpha increased in the puerarin group (P < 0. 05), the TXB2 level decreased (P < 0.05), the incidence of CVS decreased (P < 0.05), the mean MCA velocity increased (P < 0.05), and the GOS at discharge increased (P < 0.05).

CONCLUSIONSPuerarin is an effective agent for the prophylaxis and treatment of the CVS in patients after aSAH. Moreover, it can improve the prognosis. The mechanism might be correlated with improving the levels of the vascular active factors, i.e., increasing the plasma levels of NO and PGl2, decreasing TXA, in plasma, increasing the cerebral blood flow, and improving cerebral perfusion.

6-Ketoprostaglandin F1 alpha ; blood ; Adult ; Aged ; Endothelin-1 ; blood ; Female ; Humans ; Isoflavones ; therapeutic use ; Male ; Middle Aged ; Nitric Oxide ; blood ; Prognosis ; Subarachnoid Hemorrhage ; blood ; complications ; drug therapy ; Thromboxane B2 ; blood ; Vasospasm, Intracranial ; blood ; drug therapy ; etiology

OBJECTIVES: Subarachnoid hemorrhage (SAH) is a serious cerebrovascular disease. Early brain injury (EBI) and cerebral vasospasm are the main reasons for poor prognosis of SAH patients. The specific inhibitor of histone deacetylase 6 (HDAC6), tubastatin A (TubA), has been proved to have a definite neuroprotective effect on a variety of animal models of acute and chronic central nervous system diseases. However, the neuroprotective effect of TubA on SAH remains unclear. This study aims to investigate the expression and localization of HDAC6 in the early stage of SAH, and to evaluate the protective effects of TubA on EBI and cerebral vasospasm after SAH and the underlying mechanisms. METHODS: Adult male SD rats were treated with modified internal carotid artery puncture to establish SAH model. In the first part of the experiment, rats were randomly divided into 6 groups: a sham group, a SAH-3 h group, a SAH-6 h group, a SAH-12 h group, a SAH-24 h group, and a SAH-48 h group. At 3, 6, 12, and 24 h after SAH modeling, the injured cerebral cortex of rats in each group was taken for Western blotting to detect the expression of HDAC6. In addition, the distribution of HDAC6 in the cerebral cortex of the injured side was measured by immunofluorescence double staining in SAH-24 h group rats. In the second part, rats were randomly divided into 4 groups: a sham group, a SAH group, a SAH+TubA_L group (giving 25 mg/kg TubA), and a SAH+TubA_H group (giving 40 mg/kg TubA). At 24 h after modeling, the injured cerebral cortex tissue was taken for Western blotting to detect the expression levels of HDAC6, endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS), terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining to detect apoptosis, and hematoxylin and eosin (HE) staining to detect the diameter of middle cerebral artery. RESULTS: The protein expression of HDAC6 began to increase at 6 h after SAH (P<0.05), peaked at 24 h (P<0.001), and decreased at 48 h, but there was still a difference compared with the sham group (P<0.05). HDAC6 is mainly expressed in the cytoplasm of the neurons. Compared with the sham group, the neurological score was decreased significantly and brain water content was increased significantly in the SAH group (both P<0.01). Compared with the SAH group, the neurological score was increased significantly and brain water content was decreased significantly in the SAH+TubA_H group (both P<0.05), while the improvement of the above indexes was not significant in the SAH+TubA_L group (both P>0.05). Compared with the sham group, the expression of eNOS was significantly decreased (P<0.01) and the expressions of iNOS and HDAC6 were significantly increased (P<0.05 and P<0.01, respectively) in the SAH group. Compared with the SAH group, the expression of eNOS was significantly increased, and iNOS and HDAC6 were significantly decreased in the SAH+TubA group (all P<0.05). Compared with the SAH group, the number of TUNEL positive cells was significantly decreased and the diameter of middle cerebral artery was significantly increased in the SAH+TubA group (both P<0.05) . CONCLUSIONS HDAC6 is mainly expressed in neurons and is up-regulated in the cerebral cortex at the early stage of SAH. TubA has protective effects on EBI and cerebral vasospasm in SAH rats by reducing brain edema and cell apoptosis in the early stage of SAH. In addition, its effect of reducing cerebral vasospasm may be related to regulating the expression of eNOS and iNOS.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage/drug therapy* ; Vasospasm, Intracranial/metabolism* ; Histone Deacetylase Inhibitors/therapeutic use* ; Neuroprotective Agents/therapeutic use* ; Histone Deacetylase 6/pharmacology* ; Apoptosis ; Brain Injuries/drug therapy*

Fluoxetine, an anti-depressant drug, has recently been shown to provide neuroprotection in central nervous system injury, but its roles in subarachnoid hemorrhage (SAH) remain unclear. In this study, we aimed to evaluate whether fluoxetine attenuates early brain injury (EBI) after SAH. We demonstrated that intraperitoneal injection of fluoxetine (10 mg/kg per day) significantly attenuated brain edema and blood-brain barrier (BBB) disruption, microglial activation, and neuronal apoptosis in EBI after experimental SAH, as evidenced by the reduction of brain water content and Evans blue dye extravasation, prevention of disruption of the tight junction proteins zonula occludens-1, claudin-5, and occludin, a decrease of cells staining positive for Iba-1, ED-1, and TUNEL and a decline in IL-1β, IL-6, TNF-α, MDA, 3-nitrotyrosine, and 8-OHDG levels. Moreover, fluoxetine significantly improved the neurological deficits of EBI and long-term sensorimotor behavioral deficits following SAH in a rat model. These results indicated that fluoxetine has a neuroprotective effect after experimental SAH.
Animals ; Apoptosis ; drug effects ; Blood-Brain Barrier ; drug effects ; Brain Edema ; drug therapy ; etiology ; Cytokines ; genetics ; metabolism ; Disease Models, Animal ; Fluoxetine ; pharmacology ; therapeutic use ; In Situ Nick-End Labeling ; Male ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Pain Measurement ; Psychomotor Performance ; drug effects ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage ; complications ; drug therapy ; pathology ; Time Factors ; Vasospasm, Intracranial ; drug therapy ; etiology

OBJECTIVETo discuss the mechanism of cerebral vessel spasm caused by concussion and the effect of Nimodipine on concussion.

METHODSA total of 224 patients who were treated from March 1995 to October 1999 were divided into two groups randomly, ie, Nimodipine group (113 cases) and control group (111 cases). Middle cerebral artery (MCA), basilar artery (BA) and the average peak forward velocity of cerebral blood flow were observed by color three-dimensional transcranial Doppler (3D-TCD) within 24 hours after admission and at the end of 3-6 days of treatment. Cerebral blood flow changes, characteristics and treatment effect were analyzed and determined by clinical main symptom disappearance rate.

RESULTSIn concussion, cerebral blood flow was divided into 3 phases: cerebral blood flow low infusion dilation phase, cerebral blood vessel spasm phase and cerebral blood flow recovery phase. In the Nimodipine group, clinical main symptom disappearance rate was higher than that in the control group in the cerebral spasm and recovery phases with a significant difference (P < 0.01).

CONCLUSIONSCerebral vessel spasm, hypoxia and ischemia lesion are the main pathological changes. Whether cerebral dysfunction is reversible or not is mainly determined by spasm time of cerebral blood vessel. Nimodipine has a good effect on releasing spasm and diminishing the cerebral blood flow velocity. It not only improves curative effect on concussion, but also reduces and prevents concussion sequelae. Hence, concussion patients who have cerebral spasm confirmed by 3D-TCD should be given Nimodipine routinely and early.

Adolescent ; Adult ; Aged ; Blood Flow Velocity ; Brain Concussion ; complications ; diagnostic imaging ; Cerebral Arteries ; diagnostic imaging ; drug effects ; Cerebrovascular Circulation ; drug effects ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Humans ; Infusions, Intravenous ; Injury Severity Score ; Male ; Mannitol ; administration & dosage ; Middle Aged ; Nimodipine ; administration & dosage ; Reference Values ; Treatment Outcome ; Ultrasonography, Doppler, Transcranial ; Vasospasm, Intracranial ; drug therapy ; etiology ; physiopathology

BACKGROUNDThe mechanism of cerebral vasospasm following subarachnoid haemorrhage (SAH) is not understood. Here, we hypothesized that apoptosis of endothelial cells induced by p53 and its target gene em dash p53 upregulated modulator of apoptosis (PUMA) played an important role in development of cerebral vasospasm. We also observed the effects of a p53 inhibitor, pifithrin-alpha (PFT-alpha), on reducing the expression of p53 and PUMA, consequently decreasing the apoptosis of endothelial cells and alleviating cerebral vasospasm.

METHODSMale Sprague-Dawley rats weighing 300-350 g were randomly divided into five groups: a control group (sham surgery), a SAH group, a SAH+dimethyl sulfoxide (DMSO) group, a SAH + PFT-alpha (0.2 mg/kg) group and a SAH + PFT-alpha (2.0 mg/kg) group. PFT-alpha was injected intraperitoneally immediately after SAH. Rats were sacrificed 24 hours after SAH. Western blot and immunohistochemical staining were used to detect the levels of p53, PUMA and caspase-3 protein. In addition, mortality and neurological scores were assessed for each group. Statistical significance was assured by analysis of variance performed in one way ANOVA followed by the Tukey test. The neurological and mortality scores were analyzed by Dunn's method and Fisher exact test, respectively.

RESULTSAfter SAH, Western blot and immunohistochemical staining showed the levels of p53, PUMA and caspase-3 in the endothelial cells and the numbers of TdT mediated dUTP nick end labelling (TUNEL) positive endothelial cells were all significantly increased in the basilar arteries (P<0.05), but significantly reduced by PFT-alpha (P<0.05). These changes were accompanied by increasing diameters and declining wall thickness of basilar arteries (P<0.05), as well as reduced mortality and neurological deficits of the rats (P<0.05).

CONCLUSIONSPFT-alpha could protect cerebral vessels from development of vasospasm and improve neurological outcome as well as reduce the mortality via suppressing apoptosis induced by p53 in the endothelial cells of cerebral vessels.

Animals ; Apoptosis ; drug effects ; Benzothiazoles ; pharmacology ; therapeutic use ; Blotting, Western ; Disease Models, Animal ; Endothelial Cells ; drug effects ; pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage ; complications ; drug therapy ; pathology ; physiopathology ; Toluene ; analogs & derivatives ; pharmacology ; therapeutic use ; Tumor Suppressor Protein p53 ; physiology ; Vasospasm, Intracranial ; prevention & control