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*

Brain Ischemia ; Cerebral Infarction ; Humans ; Subarachnoid Hemorrhage ; Vasospasm, Intracranial/etiology*

A 50-year-old woman reported to the emergency department with thunderclap headache and vomiting. Non-enhanced brain computed tomography (CT) showed a subarachnoid hemorrhage of Hunt-Hess Grade II and Fisher Grade III. Brain angiography CT and transfemoral cerebral angiography (TFCA) revealed an aneurysm of the anterior communicating artery. A direct neck clipping was performed using the pterional approach. The post-operation CT was uneventful. Six days postoperatively, the patient became lethargic. The mean velocity (cm/s) of the middle cerebral artery peaked at 173 cm/s on the right side and 167 cm/s on the left. A TFCA revealed decreased perfusion in both recurrent arteries of Heubner (RAH), but no occlusion in either. Intra-arterial nimodipine injection was administered. On the 7th postoperative day, CT demonstrated a newly developed low-density lesion in the RAH territory bilaterally. The cause of the infarction was attributed to decreased perfusion caused by cerebral vasospasm. The patient was discharged with no definite neurologic deficit except for mild cognitive disorder.
Aneurysm ; Angiography ; Arteries* ; Brain ; Cerebral Angiography ; Emergency Service, Hospital ; Female ; Headache Disorders, Primary ; Humans ; Infarction* ; Infarction, Anterior Cerebral Artery ; Intracranial Aneurysm* ; Middle Aged ; Middle Cerebral Artery ; Neck ; Neurologic Manifestations ; Nimodipine ; Perfusion ; Subarachnoid Hemorrhage ; Vasospasm, Intracranial ; Vomiting

OBJECTIVE: The purpose of this retrospective study is to determine the accuracy of maximum intensity projection (MIP) images of computed tomographic angiography (CTA) for diagnosis of cerebral vasospasm (CV) following subarachnoid hemorrhage (SAH) compared with that of digital subtraction angiography (DSA). MATERIALS AND METHODS: For patients admitted to our hospital for SAH, MIP images of CTA and DSA were checked at admission, and images were taken again 1 week later. This protocol was used in 39 cases. MIP images of CTA and DSA examinations were reviewed by two independent readers. RESULTS: Accuracy of MIP images of CTA in various arterial segments, using DSA as the gold standard: the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for different segments varied from 84 to 97, 33–100, 84–100%, 25–85, and 79–97%, respectively, for readers. Accuracy of CTA in various vasospasm severity, using DSA as the gold standard: the sensitivity, specificity, PPV, NPV, and accuracy for different vasospasm severity varied from 44 to 100, 69–100, 36–100%, 61–100, and 88–100%, respectively, for readers. Accuracy of CTA in central segments versus peripheral segments, using DSA as the gold standard: the sensitivity, specificity, PPV, NPV, and accuracy for central segments and peripheral segments varied from 90 to 94, 68–83, 93–97%, 56–69, and 87–93%, respectively, for readers. CONCLUSION: MIP imaging of CTA is a useful modality when diagnosing CV after SAH.
Angiography* ; Angiography, Digital Subtraction* ; Diagnosis* ; Humans ; Retrospective Studies ; Sensitivity and Specificity ; Subarachnoid Hemorrhage* ; Vasospasm, Intracranial*

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

An 8-month old female presented with spontaneous subarachnoid hemorrhage and was treated successfully with endovascular coil embolization of the ruptured aneurysm. Transcranial Doppler ultrasound performed four days later demonstrated middle cerebral artery (MCA) velocities greater than 350 cm/sec on the right and greater than 200 cm/sec on the left, despite medical management. The patient demonstrated no focal neurological deficits, though examination was limited by our patient's sedation and intubation. Angiography revealed severe vasospasm of the supraclinoid internal carotid and MCA territories, bilaterally. The vasospasm was refractory to the administration of intra-arterial verapamil. Balloon angioplasty was attempted, but the device could not be advanced safely due to the small size of the patient's vessels and the stiffness of the device. A microcatheter (0.0165" diameter) was advanced over a J-shaped soft microwire (0.014" diameter) to perform mechanical angioplasty in the internal carotid artery and MCA vessels bilaterally. Dramatic improvement was seen angiographically and on transcranial Doppler, and no complications were seen.
Aneurysm ; Aneurysm, Ruptured ; Angiography ; Angioplasty ; Angioplasty, Balloon ; Carotid Artery, Internal ; Embolization, Therapeutic ; Female ; Humans ; Infant* ; Intubation ; Middle Cerebral Artery ; Subarachnoid Hemorrhage ; Ultrasonography ; Vasospasm, Intracranial* ; Verapamil

Traumatic pseudoaneurysms of middle meningeal artery (MMA) and medial sphenoid wing dural arteriovenous fistula (dAVF) are rare. These lesions usually result from traumatic brain injury, and associated with skull fracture. In this paper, the authors report a case of a patient with a ruptured traumatic pseudoaneurysm of MMA and medial sphenoid wing dAVF presented with an intracerebral hemorrhage in the left temporal region and subarachnoid hemorrhage. These lesions were completely obliterated by endovascular treatment, and the patient was recovered without any neurologic deficit. However, 18-day after the procedure, delayed neurologic deficits were developed due to cerebral vasospasm.
Aneurysm, False* ; Arteriovenous Fistula ; Brain Injuries ; Central Nervous System Vascular Malformations* ; Cerebral Hemorrhage ; Humans ; Meningeal Arteries* ; Neurologic Manifestations ; Skull Fractures ; Subarachnoid Hemorrhage* ; Subarachnoid Hemorrhage, Traumatic ; Temporal Lobe ; Vasospasm, Intracranial

Therapeutic hypothermia (TH) improves the neurological outcome in patients after cardiac arrest and neonatal hypoxic brain injury. We studied the safety and feasibility of mild TH in patients with poor-grade subarachnoid hemorrhage (SAH) after successful treatment. Patients were allocated randomly to either the TH group (34.5°C) or control group after successful clipping or coil embolization. Eleven patients received TH for 48 hours followed by 48 hours of slow rewarming. Vasospasm, delayed cerebral ischemia (DCI), functional outcome, mortality, and safety profiles were compared between groups. We enrolled 22 patients with poor-grade SAH (Hunt & Hess Scale 4, 5 and modified Fisher Scale 3, 4). In the TH group, 10 of 11 (90.9%) patients had a core body temperature of < 36°C for > 95% of the 48-hour treatment period. Fewer patients in the TH than control group (n = 11, each) had symptomatic vasospasms (18.1% vs. 36.4%, respectively) and DCI (36.3% vs. 45.6%, respectively), but these differences were not statistically significant. At 3 months, 54.5% of the TH group had a good-to-moderate functional outcome (0–3 on the modified Rankin Scale [mRS]) compared with 9.0% in the control group (P = 0.089). Mortality at 1 month was 36.3% in the control group compared with 0.0% in the TH group (P = 0.090). Mild TH is feasible and can be safely used in patients with poor-grade SAH. Additionally, it may reduce the risk of vasospasm and DCI, improving the functional outcomes and reducing mortality. A larger randomized controlled trial is warranted.
Aneurysm ; Body Temperature ; Brain Injuries ; Brain Ischemia ; Embolization, Therapeutic ; Heart Arrest ; Humans ; Hypothermia, Induced* ; Mortality ; Pilot Projects* ; Prospective Studies* ; Rewarming ; Subarachnoid Hemorrhage* ; Vasospasm, Intracranial

OBJECTIVE: The cause of severe clinical vasospasm after aneurysmal subarachnoid hemorrhage remains unknown, despite extensive research over the past 30 years. However, the intra-arterial administration of vasodilating agents and balloon angioplasty have been successfully used in severe refractory cerebral vasospasm. MATERIALS AND METHODS: We retrospectively analyzed the data of 233 patients admitted to our institute with aneurysmal subarachnoid hemorrhage (SAH) over the past 3 years. RESULTS: Of these, 27 (10.6%) developed severe symptomatic vasospasm, requiring endovascular therapy. Vasospasm occurred at an average of 5.3 days after SAH. A total of 46 endovascular procedures were performed in 27 patients. Endovascular therapy was performed once in 18 (66.7%) patients, 2 times in 4 (14.8%) patients, 3 or more times in 5 (18.5%) patients. Intra-arterial vasodilating agents were used in 44 procedures (27 with nimodipine infusion, 17 with nicardipine infusion). Balloon angioplasty was performed in only 2 (7.4%) patients. The Average nimodipine infusion volume was 2.47 mg, and nicardipine was 3.78 mg. Most patients recovered after the initial emergency room visit. Two patients (7.4%) worsened, but there were no deaths. CONCLUSION: With advances in endovascular techniques, administration of vasodilating agents and balloon angioplasty reduces the morbidity and mortality of vasospasm after aneurysmal SAH.
Aneurysm* ; Angioplasty, Balloon ; Emergency Service, Hospital ; Endovascular Procedures ; Humans ; Mortality ; Nicardipine ; Nimodipine ; Retrospective Studies ; Subarachnoid Hemorrhage* ; Vasospasm, Intracranial

Cerebral vasospasm associated with hyperthyroidism has not been reported to cause cerebral infarction. The case reported here is therefore the first of cerebral infarction co-existing with severe vasospasm and hyperthyroidism. A 30-year-old woman was transferred to our hospital in a stuporous state with right hemiparesis. At first, she complained of headache and dizziness. However, she had no neurological deficits or radiological abnormalities. She was diagnosed with hyperthyroidism 2 months ago, but she had discontinued the antithyroid medication herself three days ago. Magnetic resonance imaging and angiography showed cerebral infarction with severe vasospasm. Thus, chemical angioplasty using verapamil was performed two times, and antithyroid medication was administered. Follow-up angiography performed at 6 weeks demonstrated complete recovery of the vasospasm. At the 2-year clinical follow-up, she was alert with mild weakness and cortical blindness. Hyperthyroidism may influence cerebral vascular hemodynamics. Therefore, a sudden increase in the thyroid hormone levels in the clinical setting should be avoided to prevent cerebrovascular accidents. When neurological deterioration is noticed without primary cerebral parenchyma lesions, evaluation of thyroid function may be required before the symptoms occur.
Adult ; Angiography ; Angioplasty ; Blindness, Cortical ; Cerebral Infarction ; Dizziness ; Female ; Follow-Up Studies ; Headache ; Hemodynamics ; Humans ; Hyperthyroidism* ; Magnetic Resonance Imaging ; Paresis ; Stroke ; Stupor ; Thyroid Gland ; Vasospasm, Intracranial* ; Verapamil