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*

We present the case of a 23-year-old man who suddenly collapsed during a physical altercation with his friends while in a drunken state. The post-mortem computed tomography (CT) with angiography revealed acute basal subarachnoid hemorrhage with rupture of the left middle cerebral artery. On autopsy, the head, face, mandible and neck showed multifocal hemorrhages with fracture of the hyoid bone, and the pathologic findings of the brain was consistent with CT findings. However, the vascular rupture site was not observed macroscopically. On histologic examination, a microscopic focal rupture was identified at the proximal portion of the middle cerebral artery, and possibility of arteriopathy was considered. This case illustrates that other parts of intracerebral arteries (other than the vertebral arteries) can be the culprit of rupture in the case of traumatic basal subarachnoid hemorrhage, and the post-mortem angiographic findings can be helpful in targeting the site of vascular injury. Furthermore, meticulous sampling of intracranial vessels could help find the vascular rupture site and identify any histologic findings suspicious of arteriopathy. Therefore, we suggest that post-mortem angiography can be an effective and adjunctive tool for a tailored approach in finding the vascular injury, and that histologic examination of both the intracranial and extracranial arteries be important to medicolegally ensure the death of traumatic basal subarachnoid hemorrhage and to examine presence of arteriopathy as a predisposing factor.
Angiography ; Arteries ; Autopsy ; Brain ; Causality ; Forensic Pathology ; Friends ; Head ; Hemorrhage ; Humans ; Hyoid Bone ; Mandible ; Middle Cerebral Artery ; Neck ; Rupture ; Subarachnoid Hemorrhage ; Subarachnoid Hemorrhage, Traumatic ; Vascular System Injuries ; 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

Intracranial hemorrhage is common and is caused by diverse pathology, including trauma, hypertension, cerebral amyloid angiopathy, hemorrhagic conversion of ischemic infarction, cerebral aneurysms, cerebral arteriovenous malformations, dural arteriovenous fistula, vasculitis, and venous sinus thrombosis, among other causes. Neuroimaging is essential for the treating physician to identify the cause of hemorrhage and to understand the location and severity of hemorrhage, the risk of impending cerebral injury, and to guide often emergent patient treatment. We review CT and MRI evaluation of intracranial hemorrhage with the goal of providing a broad overview of the diverse causes and varied appearances of intracranial hemorrhage.
Arteriovenous Malformations ; Central Nervous System Vascular Malformations ; Cerebral Amyloid Angiopathy ; Cerebral Infarction ; Craniocerebral Trauma ; Hematoma, Subdural ; Hemorrhage ; Humans ; Hypertension ; Intracranial Aneurysm ; Intracranial Hemorrhages* ; Magnetic Resonance Imaging ; Neuroimaging ; Pathology ; Sinus Thrombosis, Intracranial ; Subarachnoid Hemorrhage ; Vasculitis

OBJECTIVETo explore the feasibility, safety and efficacy of endovascular reconstructive treatment by multiple overlapping stents with or without coils.

METHODSTotally 17 patients of vertebrobasilar fusiform aneurysms treated by multiple overlapping stents with or without coils between September 2011 and September 2015 in Department of Neurosurgery, Beijing Hospital were retrospectively reviewed. There were 15 male and 2 female patients with mean age of (47±13) years. Clinical manifestations included subarachnoid hemorrhage in 5 patients, cerebral ischemia or infarction in the posterior circulation in 5 patients, mass effect accompanied with brainstem infarction in 1 patients, headache or dizziness in 4, and incidental findings in 2 patients. Aneurysm located in intracranial vertebral artery in 11 patients, vertebrobasilar junction in 2 patients, and basilar trunk in 4 patients. Mean aneurysmal size was 18.5 mm×8.0 mm(length×width).

RESULTSSole stenting with overlapping stents was performed in 8 patients, and overlapping stents with coils was applied in 9 patients. Post-procedural hemorrhage occurred in a patient with a giant basilar trunk fusiform aneurysm and led to death. The 16 surviving patients were clinically followed up for a mean of 21.1 months. One patient had a modified Rankin score of 4, and the other patients had a good recovery. Among 15 patients with a mean angiographic follow-up of 8.6 months, 9 patients had their aneurysms further thrombosed, 3 patients were stable, and 3 patients with a recurred aneurysm. Final complete occlusion was achieved in 7 patients.

CONCLUSIONReconstructive treatment by overlapping stents with or without coils is feasible and relative safe in vertebrobasilar fusiform aneurysms.

Adult ; Endovascular Procedures ; Female ; Humans ; Intracranial Aneurysm ; surgery ; Male ; Middle Aged ; Retrospective Studies ; Stents ; Subarachnoid Hemorrhage ; surgery ; Treatment Outcome ; Vertebral Artery ; pathology

Early brain injury (EBI) plays a key role in the pathogenesis of subarachnoid hemorrhage (SAH). This study investigated the role of glucose-regulated protein 78 (GRP78) in EBI after SAH. Male Sprague-Dawley rats (n=108) weighing 260±40 g were divided into control, sham-operated, and operated groups. Blood was injected into the prechiasmatic cistern of rats in the operated group. Neurological scores, ultrastructures of neurons, apoptosis, and GRP78 expression in the hippocampus were examined using Garcia scoring system, transmission electron microscopy, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling, and Western blotting at 1, 6, 12, 24, 48, and 72 h after SAH, respectively. The results showed that neurological scores were significantly decreased in the operated group as compared with those in control and sham-operated groups at 12, 24, 48, and 72 h. Metachromatin, chromatin pyknosis at the edge, endoplasmic reticulum swelling, and invagination of nuclear membrane were observed at 24 h in the operated group, indicating the early morphological changes of apoptosis. The number of apoptotic cells was significantly increased in the operated group as compared with that in control and sham-operated groups at 6, 12, 24, 48, and 72 h. The GRP78 protein expression levels in the operated group were significantly elevated at all time points and reached the peak at 12 h. GRP78 expression was positively associated with apoptosis cells and negatively with neurological scores. In conclusion, EBI was demonstrated to occur after SAH and GRP78 was involved in the development of EBI after SAH.
Animals ; Apoptosis ; Brain Injuries ; complications ; metabolism ; pathology ; Chromatin ; pathology ; Endoplasmic Reticulum Stress ; Heat-Shock Proteins ; genetics ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage ; etiology ; metabolism ; pathology

Benign primary headaches are common during the postpartum period. However, there are several other kinds of headaches caused by specific underlying pathologies like post-dural puncture headache (PDPH), pregnancy induced hypertension, cortical vein thrombosis, posterior reversible encephalopathy syndrome (PRES), subarachnoid hemorrhage, intracranial hemorrhage, brain tumor, and so on. These headaches are rare but each can be life threatening conditions when diagnosis is delayed. If a patient was treated for another type of headache, like a PDPH, the diagnosis would be even more difficult. We report on the case of a 24 year-old woman who suffered with PDPH followed by postpartum eclampsia with PRES.
Diagnosis ; Eclampsia ; Female ; Headache ; Humans ; Hypertension ; Hypertension, Pregnancy-Induced ; Intracranial Hemorrhages ; Pathology ; Post-Dural Puncture Headache ; Posterior Leukoencephalopathy Syndrome* ; Postpartum Period ; Pregnancy ; Seizures ; Subarachnoid Hemorrhage ; Thrombosis ; Veins

OBJECTIVETo investigate the risk factors of progressive brain contusion and to evaluate their impact on patients' outcome.

METHODSOne hundred and thirty two patients with traumatic brain contusion were enrolled in the study, including 70 cases with progressive contusion and 62 cases with non-progressive contusion. The risk factors were investigated with univariate and multivariate Logistic regression analysis.

RESULTSThe univariate analysis showed that Glasgow Coma Score (GCS) at admission, contusion volume at the first brain CT scans, midline shift, combined with skull fracture, subarachnoid hemorrhage, epidural hematoma, subdural hematoma, location of brain contusion, D-dimer levels, combined with type 2 diabetes were associated with progressive brain contusion. Multivariate Logistic regression analysis showed that GCS at admission, contusion volume at the first CT scans, combined with subarachnoid hemorrhage, combined with type 2 diabetes were the independent risk factors for disease progression. The outcome in the progressive group was more aggravated than that in non-progressive group (P = 0.001).

CONCLUSIONPatients with disturbance of consciousness, the larger contusion volume, combined with subarachnoid hemorrhage and diabetes are at risk for progressive brain contusion and unfavorable outcome.

Brain Injuries ; complications ; pathology ; Diabetes Mellitus, Type 2 ; complications ; Disease Progression ; Fibrin Fibrinogen Degradation Products ; metabolism ; Glasgow Coma Scale ; Hematoma, Epidural, Cranial ; complications ; Hematoma, Subdural ; complications ; Humans ; Risk Factors ; Subarachnoid Hemorrhage ; complications ; Tomography, X-Ray Computed

Cerebral amyloid angiopathy (CAA) involves cerebrovascular amyloid deposition and is classified into several types according to the amyloid protein involved. Of these, sporadic amyloid beta-protein (Abeta)-type CAA is most commonly found in older individuals and in patients with Alzheimer's disease (AD). Cerebrovascular Abeta deposits accompany functional and pathological changes in cerebral blood vessels (CAA-associated vasculopathies). CAA-associated vasculopathies lead to development of hemorrhagic lesions [lobar intracerebral macrohemorrhage, cortical microhemorrhage, and cortical superficial siderosis (cSS)/focal convexity subarachnoid hemorrhage (SAH)], ischemic lesions (cortical infarction and ischemic changes of the white matter), and encephalopathies that include subacute leukoencephalopathy caused by CAA-associated inflammation/angiitis. Thus, CAA is related to dementia, stroke, and encephalopathies. Recent advances in diagnostic procedures, particularly neuroimaging, have enabled us to establish a clinical diagnosis of CAA without brain biopsies. Sensitive magnetic resonance imaging (MRI) methods, such as gradient-echo T2* imaging and susceptibility-weighted imaging, are useful for detecting cortical microhemorrhages and cSS. Amyloid imaging with amyloid-binding positron emission tomography (PET) ligands, such as Pittsburgh Compound B, can detect CAA, although they cannot discriminate vascular from parenchymal amyloid deposits. In addition, cerebrospinal fluid markers may be useful, including levels of Abeta40 for CAA and anti-Abeta antibody for CAA-related inflammation. Moreover, cSS is closely associated with transient focal neurological episodes (TFNE). CAA-related inflammation/angiitis shares pathophysiology with amyloid-related imaging abnormalities (ARIA) induced by Abeta immunotherapies in AD patients. This article reviews CAA and CAA-related disorders with respect to their epidemiology, pathology, pathophysiology, clinical features, biomarkers, diagnosis, treatment, risk factors, and future perspectives.
Alzheimer Disease ; Amyloid ; Amyloid beta-Peptides ; Biomarkers ; Biopsy ; Blood Vessels ; Brain ; Cerebral Amyloid Angiopathy* ; Cerebrospinal Fluid ; Cerebrovascular Disorders ; Dementia ; Diagnosis ; Epidemiology ; Humans ; Immunotherapy ; Infarction ; Inflammation ; Leukoencephalopathies ; Ligands ; Magnetic Resonance Imaging ; Neuroimaging ; Pathology ; Plaque, Amyloid ; Positron-Emission Tomography ; Risk Factors ; Siderosis ; Stroke ; Subarachnoid Hemorrhage

OBJECTIVETo investigate the association of hypoxia-inducible factor-1α (HIF-1α) expression and apoptosis in the cerebral cortex following subarachnoid hemorrhage (SAH).

METHODSSubarachnoid hemorrhage was induced by modified monofilament puncture method in rats. Thirty-five adult male Sprague-Dawley rats were randomly assigned to five groups: sham-operated group, SAH 6 h, SAH 12 h, SAH 24 h and SAH 72 h groups. HIF-1α expression was assessed by immunofluorescence staining. TdT-mediated dUTP-biotin nick end-labeling (TUNEL) technique was adopted to detect apoptotic cells. Double immunolabeling was used to identify cell types with positive HIF-1α expression.

RESULTSThe expression of HIF-1α was increased at 6 h (4.65%±1.01%), peaked at 24 h (18.55%±4.23%), and decreased at 72 h (6.31%±1.15%) after SAH (P<0.05). TUNEL-positive cells were up-regulated in the brain at 6 h (7.09%±2.34%), peaked at 24 h (25.54%±7.36%), and down-regulated at 72 h (14.11%±3.03%) after SAH (P<0.05). A significant positive correlation was noted between HIF-1α positive rates and TUNEL positive rates following SAH (r=0.738, P<0.05). Double immunolabeling indicated that HIF-1α was expressed predominantly in neurons and some nuclei with positive HIF-1α were co-stained with TUNEL.

CONCLUSIONThe data indicate that HIF-1α might participate in the pathological progression of early brain injury after SAH.

Animals ; Apoptosis ; Brain ; metabolism ; pathology ; Disease Models, Animal ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage ; metabolism ; pathology