OBJECTIVETo compare the efficacy of 3% hypertonic saline solution with 20% mannitol in treatment of intracranial hypertension in patients with aneurysmal subarachnoid hemorrhage.

METHODSAn alternating treatment protocol was used to compare the efficacy of 160 mL 3% hypertonic saline solution (HSS) with 150 mL 20% mannitol for episodes of increased intracranial pressure (ICP) in patients with aneurysmal subarachnoid hemorrhage. The dependent variables were the extent and duration of reduction of increased ICP after each event.

RESULTSBoth 3% HSS and 20% mannitol rapidly decreased the ICP in patients with aneurysmal subarachnoid hemorrhage (P <0.01). No difference between two medications in the extent of duration of ICP and reduction of action (P >0.05).

CONCLUSION3% HSS should be considered as the first-line osmotic drug in treatment of intracranial hypertension in patients with aneurysmal subarachnoid hemorrhage.

Humans ; Intracranial Hypertension ; drug therapy ; Mannitol ; therapeutic use ; Saline Solution, Hypertonic ; therapeutic use ; Subarachnoid Hemorrhage ; drug therapy ; Treatment Outcome

Forty-three patients with aneurysmal subarachnoid hemorrhage entered a nimodipine trial in the Department of Neurosurgery, Yonsei university to determine the efficacy of the drug in preventing vasospasm and to evaluate the tolerability of this calcium channel blocker. Thirty-three patients completed the study. Treatment was started within four days of initial bleeding and continued for two weeks. Delayed neurological deficits developed in seven of the 33 patients-four from vasospasm, two from elevated intracranial pressure, and one from recurrent bleeding. The incidence of symptomatic vasospasm which developed after calcium channel blocker (nimodipine) treatment was 12.1%, which is about one third of the rate experienced at our department during the past five years (33.2%). Twenty-five patients were operated on without surgical mortality and the morbidity rate was 8%. Side effects due to nimodipine treatment were reversible and insignificant. This study suggests that treatment with a calcium channel blocker that has a selective cerebrovascular effect may prevent or reduce the incidence of delayed ischemic deficits in patients with aneurysmal subarachnoid hemorrhage.
Clinical Trials ; Human ; Ischemic Attack, Transient/prevention & control* ; Nimodipine/therapeutic use* ; Prospective Studies ; Subarachnoid Hemorrhage/drug therapy*

Animals ; Apoptosis ; Brain/metabolism* ; Male ; Phosphatidylinositol 3-Kinases/metabolism* ; Rats ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage/drug therapy* ; Thyroxine/pharmacology*

Diagnosis, Differential ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Phytotherapy ; Subarachnoid Hemorrhage ; diagnosis ; drug therapy ; Syndrome ; Vasodilator Agents ; therapeutic use

The authors report 2 cases of metastatic choriocarcinoma associated with intracranial hemorrhage. One of them had intracranial hemorrhage on the right frontal lobe and the other one developed intracranial hemorrhage and enhancing mass on the parietal lobe revealed by admission brain CT. They had rebled intracranially 2 and 3 times, respectively. Even though the patients had received intracranial decompressive operations, they eventually died of intracranial rebleeding or hemothorax, respectively. These tumors generally occur in women of childbearing age and commonly produce signs and symptoms of subarachnoid hemorrhage, intracerebral hemorrhage, or brain tumor. Metastatic choriocarcinoma of the brain is a curable lesion. Cure is geerally achieved by extirpation of the tumor, chemotherapy, and irradiation of the site of the cerebral metastasis. The two cases in this report have ben unsuccessful in their management.
Brain ; Brain Neoplasms ; Cerebral Hemorrhage ; Choriocarcinoma* ; Drug Therapy ; Female ; Frontal Lobe ; Hemothorax ; Humans ; Intracranial Hemorrhages* ; Neoplasm Metastasis ; Parietal Lobe ; Pregnancy ; Subarachnoid Hemorrhage

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

BACKGROUNDThe underlying mechanism of early neurobiological impairment after subarachnoid hemorrhage (SAH) is not well understood, but the system of reactive oxygen superoxide (ROS) might be involved. Edaravone (MCI-186), a potent free radical scavenger that prevents apoptosis of neurons, was thus used in this study to see its possible therapeutic effect in early brain injury due to SAH in a rat model.

METHODSOne hundred and twenty male Sprague-Dawley rats were randomly assigned to four groups: group 1, control rats receiving sham operation only; group 2, rats with SAH treated by saline; group 3, rats with SAH treated with 1 mg/kg MCI-186 injected intraperitoneally; and group 4, rats with SAH treated with 3 mg/kg MCI-186. Treated with either saline or MCI-186 twice daily for two consecutive days after SAH, the rats were sacrificed for measurements of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) and histological analysis of caspase-3 protein by Western blotting and immunohistochemical staining. In addition, mortality and neurological scores were statistically analyzed by the chi-square test and Dunn's procedure respectively for each group. One-way analysis of variance followed by the Tukey's procedure was also used in data analysis.

RESULTSThe rats in group 2 that received saline only showed neurological impairment as well as elevated mortality, and were found to have significantly increased levels of MDA and caspase-3, but reduced SOD activities in brain tissues (P < 0.05). When treated with MCI-186 at two different dosages, the rats in groups 3 and 4 had markedly decreased levels of MDA and caspase-3 but increased SOD activities in the brain tissue (P < 0.05), along with improved scores of neurological evaluation (P < 0.05).

CONCLUSIONSThis study sheds some lights on the therapy of SAH-induced early brain injury by providing the promising data indicating that MCI-186, a radical scavenger, can efficiently diminish apoptosis of neurons and thus prevent the function loss of the brain in rats with SAH.

Animals ; Antipyrine ; analogs & derivatives ; therapeutic use ; Blotting, Western ; Brain Injuries ; drug therapy ; etiology ; Immunohistochemistry ; Male ; Malondialdehyde ; metabolism ; Neuroprotective Agents ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage ; physiopathology ; Superoxide Dismutase ; metabolism

Rho kinase, also named Rho associated kinase, is one of the important kinases found in recent ten years, which regulates cell movement including cytodieresis, contraction, adherence, migration, secretion, etc. The Rho kinase up-regulation in activity or in expression involves the progress of cardio-cerebro-vascular disorders, and Rho kinase has been regarded as a key target in drug discovery and development. With more and more Rho kinase inhibitors popping up, Rho kinase inhibitors are becoming a promising solution to cardiovascular diseases, neural disorders and other diseases. The article reviews the advances in the study of Rho kinase pathway andits inhibitors, other information associated with Rho kinase is also discussed.
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine ; analogs & derivatives ; chemistry ; pharmacology ; therapeutic use ; Amides ; chemistry ; therapeutic use ; Antihypertensive Agents ; pharmacology ; therapeutic use ; Cardiovascular Diseases ; drug therapy ; Humans ; Pyridines ; chemistry ; therapeutic use ; Signal Transduction ; Subarachnoid Hemorrhage ; drug therapy ; Vasodilator Agents ; pharmacology ; therapeutic use ; rho-Associated Kinases ; antagonists & inhibitors ; chemistry ; metabolism