2020年 · 第06卷第01期

Cerebral cavernous malformations (CCMs), a major neurosurgical condition, characterized by abnormally dilated intracranial capillaries, result in increased susceptibility to stroke. KRIT1 (CCM1), MGC4607 (CCM2), and PDCD10 (CCM3) have been identified as causes of CCMs in which at least one of them is disrupted in most familial cases. Our goal is to identify potential biomarkers and genetic modifiers of CCMs, using a global comparative omics approach across several in vitro studies and multiple in vivo animal models. We hypothesize that through analysis of the CSC utilizing various omics, we can identify potential biomarkers and genetic modifiers, by systemically evaluating effectors and binding partners of the CSC as well as second layer interactors.

We utilize a comparative omics approach analyzing multiple CCMs deficient animal models across nine independent studies at the genomic, transcriptomic, and proteomic levels to dissect alterations in various signaling cascades.

Our analysis revealed a large set of genes that were validated across multiple independent studies, suggesting an important role for these identified genes in CCM pathogenesis.

This is currently one of the largest comparative omics analysis of CCM deficiencies across multiple models, allowing us to investigate global alterations among multiple signaling cascades involved in both angiogenic and non-angiogenic events and to also identify potential biomarker candidates of CCMs, which can be used for new therapeutic strategies.

Subarachnoid hemorrhage (SAH), an acute cerebrovascular accident, features with its high death and disability rate. Sirtuin3 (SIRT3) is a NAD+ dependent deacetylase which mainly located in mitochondria. Reduced SIRT3 function was indicated to involve in many disorders of central nervous system. Herein, we aimed to explore the neuroprotective effects of SIRT3 on SAH and to furtherly explore the underlying mechanisms.

Adult C57BL/6 J male mice (8-10 weeks) were used to establish SAH models. The pharmacological agonist of SIRT3, Honokiol (HKL), was injected in an intraperitoneal manner (10 mg/kg) immediately after the operation. Brain edema and neurobehavioral score were assessed. Nissl staining and FJC staining were used to evaluate the extent of neuronal damage. The changes of mitochondria morphology were observed with transmission electron microscopy. Western blot was used for analyzing the protein level of SIRT3 and the downstream signaling molecules.

SIRT3 was downregulated after SAH, and additional treatment of SIRT3 agonist HKL alleviated brain edema and neurobehavioral deficits after SAH. Additionally, electron microscopy showed that HKL significantly alleviated the morphological damage of mitochondria induced by SAH. Further studies showed that HKL could increase the level of mitochondrial fusion protein Mfn1 and Mfn2, thus maintaining (mitochondrial morphology), protecting mitochondrial function and promoting neural survival. While, additional Compound C (CC) treatment, a selective AMPK inhibitor, abolished these protective effects.

Activation of SIRT3 protects against SAH injury through improving mitochondrial fusion in an AMPK dependent manner.

Moyamoya disease (MMD) is a relatively important and common disease, especially in East Asian children. There are few reports about EEG in children with MMD in China till now. This study is aimed to analyze the electroencephalographic features of MMD in pediatric patients in China preliminarily.

Pediatric patients with MMD who were hospitalized in Peking University International Hospital and Beijing Tiantan Hospital from January 2016 to December 2018 were collected. Clinical and electroencephalography (EEG) findings were analyzed retrospectively.

A total of 110 pediatric patients with MMD were involved, and 17 (15.5%) cases had a history of seizure or epilepsy. Ischemic stroke was associated with a 1.62-fold relative risk of seizure. A subset of 15 patients with complete EEG data was identified. Indications for EEG in patients with MMD included limb shaking, unilateral weakness, or generalized convulsion. Abnormal EEG was seen in 14 (93.3%) cases, with the most common findings being focal slowing 12 (80.0%), followed by epileptiform discharge 10 (66.7%), and diffuse slowing 9 (60.0%). "Rebuild up" phenomenon on EEG was observed in one patient.

Seizure and abnormal background activity or epileptiform discharge on EEG were common in pediatric patients with MMD. EEG may play a role in differential diagnosis among the transient neurological events in MMD such as transient ischemic attack and seizure.

The development of carotid-cavernous fistulas (CCFs) during surgical recanalization of chronic internal carotid artery occlusion (ICAO) may be secondary to severe ICA dissection rather than a focal tear of the cavernous ICA seen in typical traumatic CCFs. The purpose of this study is to investigate the causal relationship between the CCFs and severe ICA dissections and to characterize technical outcomes after treatment with stenting.

Five patients underwent treatment with self-expanding stents due to intraprocedural CCF and ICA dissection following surgical removal of ICAO plaque. The stents were telescopically placed via true channel of the dissection. Safety of the procedure was evaluated with 30-day stroke and death rate. Procedural success was determined by the efficacy of CCF obliteration and ICAO recanalization with angiography.

All CCFs were associated with spiral and long segmental dissection from the cervical to cavernous ICA. After stenting, successful dissection reconstruction with TICI 3 was achieved in all patients, with complete (n = 4) or partial CCF (n = 1) obliteration. No patient had CCF syndrome, stroke, or death during follow-up of 6 to 37 months; but one patient had pulsatile tinnitus, which resolved 1 year later. Angiography at 6 to 24 months demonstrated CCF obliteration in all 5 patients and durable ICA patency in 4 patients.

Intraprocedural CCFs with spiral and cervical-to-cavernous ICA dissection during ICAO surgery are dissection-related because of successful obliteration after stenting for dissection reconstruction. Self-expanding stenting through true channel of the dissection, serving as implanting stent-autograft, may be an optimal therapy for the atypical CCF complication from ICAO surgery.

Stroke is a devastating disease that occurs when a blood vessel in the brain is either blocked or ruptured, consequently leading to deficits in neurological function. Stroke consistently ranked as one of the top causes of mortality, and with the mean age of incidence decreasing, there is renewed interest to seek novel therapeutic treatments. The Scavenger Receptor Class B type 1 (SR-B1) is a multifunctional protein found on the surface of a variety of cells. Research has found that that SR-B1 primarily functions in an anti-inflammatory and antiatherosclerotic capacity. In this review, we discuss the characteristics of SR-B1 and focus on its potential correlation with the modifiable risk factors of stroke. SR-B1 likely has an impact on stroke through its interaction with smoking, diabetes mellitus, diet, physical inactivity, obesity, hypercholesterolemia, atherosclerosis, coronary heart disease, hypertension, and sickle cell disease, all of which are critical risk factors in the pathogenesis of stroke.

Neurosurgical procedures cause inevitable brain damage from the multitude of surgical manipulations utilized. Incisions, retraction, thermal damage from electrocautery, and intraoperative hemorrhage cause immediate and long-term brain injuries that are directly linked to neurosurgical operations, and these types of injuries, collectively, have been termed surgical brain injury (SBI). For the past decade, a model developed to study the underlying brain pathologies resulting from SBI has provided insight on cellular mechanisms and potential therapeutic targets. This model, as seen in a rat, mouse, and rabbit, mimics a neurosurgical operation and causes commonly encountered post-operative complications such as brain edema, neuroinflammation, and hemorrhage. In this review, we elaborate on SBI and its clinical impact, the SBI animal models and their clinical relevance, the importance of applying therapeutics before neurosurgical procedures (i.e., preconditioning), and the new direction of applying venom-derived proteins to attenuate SBI.

Giant serpentine aneurysms (GSA) originate from saccular or spindle aneurysm, dissimilar from dissected aneurysm, that are defined as partially thrombosed giant aneurysms with tortuous internal vascular channel. The clinical and neuroradiologic characteristics are clarified and the mechanism of formation and the efficacy of double stent implantation in GSA are discussed.

An 18-year-old man presented himself with a GSA arising from the internal cerebral artery (ICA). In addition, a mandibular aneurysm (MA) arose from the external cerebral artery (ECA). Success was achieved in treating GSA through endovascular treatment with double stents implanted in the parent artery, which were LEO stent and Tubridge flow diverter. After 1 year of follow-up, three-dimensional reconstruction of blood vessels revealed the disappearance of the serpentine access of GSA, which was found to be replaced with a roughly normal vascular structure.

Double stent implantation has provided a feasible treatment option for giant serpentine internal carotid aneurysms and eliminated the possibility of causing collateral circulation occlusion. Therefore, it represents a simple and suitable treatment method for anatomical structure and operation.