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*

OBJECTIVE: To determine whether Schisandrin B (Sch B) attenuates early brain injury (EBI) in rats with subarachnoid hemorrhage (SAH). METHODS: Sprague-Dawley rats were divided into sham (sham operation), SAH, SAH+vehicle, and SAH+Sch B groups using a random number table. Rats underwent SAH by endovascular perforation and received Sch B (100 mg/kg) or normal saline after 2 and 12 h of SAH. SAH grading, neurological scores, brain water content, Evan's blue extravasation, and terminal transferase-mediated dUTP nick end-labeling (TUNEL) staining were carried out 24 h after SAH. Immunofluorescent staining was performed to detect the expressions of ionized calcium binding adapter molecule 1 (Iba-1) and myeloperoxidase (MPO) in the rat brain, while the expressions of B-cell lymphoma 2 (Bcl-2), Bax, Caspase-3, nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis-associated specklike protein containing the caspase-1 activator domain (ASC), Caspase-1, interleukin (IL)-1β, and IL-18 in the rat brains were detected by Western blot. RESULTS: Compared with the SAH group, Sch B significantly improved the neurological function, reduced brain water content, Evan's blue content, and apoptotic cells number in the brain of rats (P<0.05 or P<0.01). Moreover, Sch B decreased SAH-induced expressions of Iba-1 and MPO (P<0.01). SAH caused the elevated expressions of Bax, Caspase-3, NLRP3, ASC, Caspase-1, IL-1β, and IL-18 in the rat brain (P<0.01), all of which were inhibited by Sch B (P<0.01). In addition, Sch B increased the Bcl-2 expression (P<0.01). CONCLUSION Sch B attenuated SAH-induced EBI, which might be associated with the inhibition of neuroinflammation, neuronal apoptosis, and the NLRP3 inflammatory signaling pathway.
Animals ; Apoptosis ; Brain/pathology* ; Brain Injuries/pathology* ; Caspase 3/metabolism* ; Cyclooctanes ; Evans Blue ; Inflammasomes/metabolism* ; Interleukin-18/metabolism* ; Lignans ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Polycyclic Compounds ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Rats ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage/drug therapy* ; Water ; bcl-2-Associated X Protein/metabolism*

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

PURPOSE: Contrast-induced acute kidney injury (CI-AKI) is associated with poor outcomes after percutaneous coronary intervention. However, CI-AKI has rarely been evaluated within the neurovascular field. The aim of this study was to investigate the incidence and clinical implication of CI-AKI after coil embolization in patients with an aneurysmal subarachnoid hemorrhage (aSAH). MATERIALS AND METHODS: Between January 2005 and March 2016, 192 patients who underwent coil embolization were enrolled in this study. CI-AKI was defined as an increase from baseline serum creatinine concentration of >25% or >0.5 mg/dL within 72 hours after coil embolization. A poor clinical outcome was defined as a score of ≥3 on the modified Rankin Scale at one-year post-treatment. RESULTS: A total of 16 patients (8.3%) died as a result of medical problems within one year. CI-AKI was identified in 14 patients (7.3%). Prominent risk factors for one-year mortality included CI-AKI [odds ratio (OR): 16.856; 95% confidence interval (CI): 3.437–82.664] and an initial Glasgow Coma Scale (GCS) score ≤8 (OR: 5.565; 95% CI: 1.703–18.184). A poor clinical outcome was associated with old age (≥65 years) (OR: 7.921; 95% CI: 2.977–21.076), CI-AKI (OR: 11.281; 95% CI: 2.138–59.525), an initial GCS score ≤8 (OR 31.02; 95% CI, 10.669–90.187), and a ruptured aneurysm (p=0.016, OR: 4.278) in posterior circulation. CONCLUSION: CI-AKI seems to be an independent predictor of the overall outcomes of aSAH after endovascular treatment.
Acute Kidney Injury/chemically induced ; Acute Kidney Injury/diagnostic imaging ; Acute Kidney Injury/etiology ; Acute Kidney Injury/mortality ; Adult ; Aged ; Aged, 80 and over ; Aneurysm/complications ; Aneurysm/diagnostic imaging ; Aneurysm/therapy ; Angiography ; Contrast Media/adverse effects ; Embolization, Therapeutic/adverse effects ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Subarachnoid Hemorrhage/complications ; Subarachnoid Hemorrhage/diagnostic imaging ; Subarachnoid Hemorrhage/therapy ; Treatment Outcome ; Young Adult

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

BACKGROUND: An incidental finding of unruptured aneurysm, which is a contraindication to the recombinant tissue plasminogen activator (rtPA), is common in patients with acute ischemic strokes. However, reports describing the rupture of intracranial aneurysm following the administration of rtPA are extremely rare. CASE REPORT: A 51-year-old man presented to the emergency room with global aphasia. A computed tomography (CT) of the brain revealed no intracranial hemorrhage. Since global aphasia occurred in an hour, rtPA was administrated intravenously. A CT angiography was performed 2 hours after an infusion of rtPA, which despite the absence of neurological deterioration and blood pressure surge, revealed subarachnoid hemorrhage in the right cerebral hemisphere, in addition to a 3-mm saccular aneurysm with a bleb in the right middle cerebral artery. CONCLUSIONS: Aneurysmal subarachnoid hemorrhage can develop following the infusion of rtPA. Hence, unruptured aneurysm may not simply be an “incidental finding” in stroke patients receiving rtPA.
Aneurysm ; Angiography ; Aphasia ; Blister ; Blood Pressure ; Brain ; Cerebral Infarction ; Cerebrum ; Emergency Service, Hospital ; Humans ; Incidental Findings ; Intracranial Aneurysm ; Intracranial Hemorrhages ; Middle Aged ; Middle Cerebral Artery ; Rupture ; Stroke ; Subarachnoid Hemorrhage ; Thrombolytic Therapy ; Tissue Plasminogen Activator

OBJECTIVE: To report effects of the pre-procedural rehydration for reduce thromboembolic complications in acute phase aneurysmal subarachnoid hemorrhage coil embolization. MATERIALS AND METHODS: From January 2009 to December 2013, 190 patients with ruptured aneurysmal subarachnoid hemorrhage (aSAH) treated by coil embolization at our institution were consecutively enrolled in this study. In period 1 (from January 2009 to June 2012, n = 122), pre-procedural fluid was not supplied. In period 2 (from July 2012 to December 2013, n = 68), depending on the state of the patient's body weight and degree of dehydration, intravenous fluid was started with infusion of approximately 7 mL/kg of 0.9 percent saline (minimum 300 to maximum 500 mL) over 30 minutes. RESULTS: A total of 190 patients were hospitalized due to aSAH and underwent coil embolization for five years between January 2009 and December 2013. Of these, 122 patients underwent coil embolization based on the old protocol before June 2012 (period 1) and 68 underwent the procedure based on the new protocol after the period 2. Neck size, width, maximum diameter of the aneurysm and procedure time were associated with procedure related thromboembolic complications in entire periods (multivariate analysis, p < 0.05, in respectively). The frequency of thromboembolism showed a drastic decrease in period 2 (re-hydration period), from 18.0% (22/123) to 4.4% (3/67), which was also statistically significant (p = 0.007, Chi-square test). CONCLUSION: Pre-procedural administration of a sufficient dose of fluid considering the patient's dehydration reduced the frequency of thromboembolism in cases of emergency coil embolization for ruptured aneurysm, without increasing additional specific complications.
Aneurysm ; Aneurysm, Ruptured* ; Body Weight ; Dehydration ; Embolization, Therapeutic ; Emergencies ; Fluid Therapy* ; Humans ; Neck ; Rehydration Solutions ; Subarachnoid Hemorrhage ; Thromboembolism

BACKGROUND AND PURPOSE: The claims data of the Korean National Health Insurance (NHI) system can be useful in stroke research. The aim of this study was to validate the accuracy of hospital discharge data used for NHI claims in identifying acute stroke and use of thrombolytic therapy. METHODS: The hospital discharge data of 1,811 patients with stroke-related diagnosis codes were obtained from Jeju National University Hospital (JNUH) and Seoul Medical Center (SMC). Three algorithms were tested to identify discharges with acute stroke [ischemic stroke (IS), intracranial hemorrhage (ICH), or subarachnoid hemorrhage (SAH)]: 1) all diagnosis codes up to nine positions, 2) one primary diagnosis and one secondary diagnosis, and 3) only one primary diagnosis code. Reviews of medical records were considered the gold standards. RESULTS: Overall, the degree of agreement (kappa) was higher for algorithms 1 and 2 than for algorithm 3, and the sensitivity and specificity of the first two algorithms for IS and SAH were both >90%, with almost perfect agreement (kappa=0.83-0.84) in the JNUH data set. Regarding ICH, only algorithm 1 yielded an almost perfect agreement (kappa=0.82). In the SMC data set, almost perfect agreement was found for both ICH and SAH in all three algorithms. In contrast, the three algorithms yielded a range of agreement levels, though all substantial, for IS. Almost perfect agreement was obtained for use of thrombolytic therapy in both data sets (kappa=0.91-0.99). CONCLUSIONS: Discharge with hemorrhagic stroke and use of thrombolytic therapy were identified with high reliability in administrative discharge data. A substantial level of agreement was also obtained for IS, despite variation between the algorithms and data sets.
Data Collection ; Dataset ; Diagnosis ; Hospital Records ; Humans ; Intracranial Hemorrhages ; Medical Records ; National Health Programs* ; Sensitivity and Specificity ; Seoul ; Stroke* ; Subarachnoid Hemorrhage ; Thrombolytic Therapy*

Prompt diagnosis and appropriate transport of patients with subarachnoid hemorrhage (SAH) is critical. We aimed to study differences in clinical outcomes by emergency medical services (EMS) usage and interhospital transfer in patients with SAH. We analyzed the CAVAS (CArdioVAscular disease Surveillance) database which is an emergency department-based, national cohort of cardiovascular disease in Korea. Eligible patients were adults with non-traumatic SAH diagnosed between January 2007 and December 2012. We excluded those whose EMS use and intershopital transfer data was unknown. The primary and secondary outcomes were mortality and neurologic status at discharge respectively. We compared the outcomes between each group using multivariable logistic regressions, adjusting for sex, age, underlying disease, visit time and social history. Of 5,461 patients with SAH, a total of 2,645 were enrolled. Among those, 258 used EMS and were transferred from another hospital, 686 used EMS only, 1,244 were transferred only, and 457 did not use EMS nor were transferred. In the regression analysis, mortality was higher in patients who used EMS and were transferred (OR 1.40, 95% CI 1.02-1.92), but neurologic disability was not meaningfully different by EMS usage and interhospital transfer. In Korea, SAH patients' mortality is higher in the case of EMS use or receiving interhospital transfer.
Adult ; Aged ; Emergency Medical Services/*utilization ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Outcome Assessment (Health Care) ; Patient Transfer/*utilization ; Republic of Korea/epidemiology ; Retrospective Studies ; Subarachnoid Hemorrhage/mortality/*therapy

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