Association of Renal Dysfunction With Remote Diffusion-Weighted Imaging Lesions and Total Burden of Cerebral Small Vessel Disease in Patients With Primary Intracerebral Hemorrhage.

Objective: Remote diffusion-weighted imaging (DWI) lesions (R-DWIL) found in intracerebral hemorrhage (ICH) patients are considered as an additional marker of cerebral small vessel disease (cSVD). This study aimed to investigate the association of renal dysfunction and R-DWIL, as well as the total burden of cSVD on magnetic resonance imaging among patients with primary ICH. Methods: One hundred and twenty-six consecutive patients were prospectively enrolled. R-DWIL on DWI, as well as other imaging markers of cSVD, including lacunes, white matter lesions, cerebral microbleeds, and enlarged perivascular spaces were rated using validated scales. Renal dysfunction was evaluated either by reduced estimated glomerular filtration rate (eGFR) or the presence of proteinuria or increased cystatin C. Results: After adjustments for potential confounders by logistic regression, impaired eGFR [odds ratio (OR) 6.00, 95% confidence interval (CI) 1.73-20.78], proteinuria (OR 3.07, 95% CI 1.25-7.54) and increased cystatin C (OR 2.73, 95% CI 1.11-6.72) were correlated with presence of R-DWIL. A similar association was also found between cystatin C levels (OR 3.16, 95% CI 1.39-7.19), proteinuria (OR 2.79, 95% CI 1.34-5.83) and the comprehensive cSVD burden. Conclusions: Renal dysfunction are associated with the presence of R-DWIL, and total burden of cSVD in patients with primary ICH.

Congenital anomaly of the posterior arch of the atlas: a rare risk factor for posterior circulation stroke.

We report an extremely rare case involving a posterior arch anomaly of the atlas, causing a vertebral artery dissection (VAD) induced posterior circulation stroke. A 16-year-old girl was admitted to hospital because of new onset dizziness. VAD related multiple infarction in the posterior circulation was revealed. The congenital posterior arch anomaly of the atlas, along with instability of the atlantoaxial joint, were discovered accidentally during follow-up. This is the first case of ischemic stroke related to atlantal posterior arch aplasia and atlantoaxial instability. Although rare, it reminds us that investigation of the craniovertebral junction should be considered when stroke occurs in young patients.

Recombinant Gas6 augments Axl and facilitates immune restoration in an intracerebral hemorrhage mouse model.

Axl, a tyrosine kinase receptor, was recently identified as an essential component regulating innate immune response. Suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3 are potent Axl-inducible negative inflammatory regulators. This study investigated the role of Axl signaling pathway in immune restoration in an autologous blood-injection mouse model of intracerebral hemorrhage. Recombinant growth arrest-specific 6 (Gas6) and R428 were administrated as specific agonist and antagonist. In vivo knockdown of Axl or suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3 by siRNA was applied. After intracerebral hemorrhage, the expression of endogenous Axl, soluble Axl, and Gas6 was increased, whereas the expression of suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3 was inhibited. Recombinant growth arrest-specific 6 administration alleviated brain edema and improved neurobehavioral performances. Moreover, enhanced Axl phosphorylation with cleavage of soluble Axl (sAxl), and an upregulation of suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3 were observed. In vivo knockdown of Axl and R428 administration both abolished the effect of recombinant growth arrest-specific 6 on brain edema and also decreased the expression suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3. In vivo knockdown of suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3 aggravated cytokine releasing despite of recombinant growth arrest-specific 6. In conclusion, Axl plays essential role in immune restoration after intracerebral hemorrhage. And recombinant growth arrest-specific 6 attenuated brain injury after intracerebral hemorrhage, probably by enhancing Axl phosphorylation and production of suppressor of cytokine signaling 1 and suppressor of cytokine signaling 3.

Hyperbaric Oxygen Preconditioning Attenuates Hemorrhagic Transformation Through Reactive Oxygen Species/Thioredoxin-Interacting Protein/Nod-Like Receptor Protein 3 Pathway in Hyperglycemic Middle Cerebral Artery Occlusion Rats.

OBJECTIVES: To clarify whether hyperbaric oxygen preconditioning can attenuate hyperglycemia-enhanced hemorrhagic transformation and to establish a role for Nod-like receptor protein 3 inflammasome in the pathophysiology of hemorrhagic transformation. DESIGN: Controlled prospective animal study. SETTING: University research laboratory. SUBJECTS: Male Sprague-Dawley rats weighing 260-280 g. INTERVENTIONS: Rats received 1-hour-long hyperbaric oxygen preconditioning for five consecutive days. Hyperglycemic middle cerebral artery occlusion model was induced at 24 hours after the last hyperbaric oxygen exposure. Reactive oxygen species scavenger (N-acetyl-L-cysteine), thioredoxin-interacting protein small interfering RNA, and Nod-like receptor protein 3 small interfering RNA were given in different groups separately to verify the possible pathway. MEASUREMENTS AND MAIN RESULTS: Rats were randomly divided into sham, middle cerebral artery occlusion, middle cerebral artery occlusion + dextrose, middle cerebral artery occlusion + dextrose + normobaric oxygen preconditioning, middle cerebral artery occlusion + dextrose + hyperbaric oxygen, middle cerebral artery occlusion + dextrose + hyperbaric oxygen + N-acetyl-L-cysteine, middle cerebral artery occlusion + dextrose + hyperbaric oxygen + control small interfering RNA, middle cerebral artery occlusion + dextrose + hyperbaric oxygen + thioredoxin-interacting protein small interfering RNA, and middle cerebral artery occlusion + dextrose + hyperbaric oxygen + Nod-like receptor protein 3 small interfering RNA groups. Hyperglycemia was induced by administration of 50% dextrose (6 mL/kg) intraperitoneally 30 minutes before middle cerebral artery occlusion. Control small interfering RNA/thioredoxin-interacting protein small interfering RNA or Nod-like receptor protein 3 small interfering RNA (500 pmol/5 µL) were injected intracerebroventricularly 72 hours before middle cerebral artery occlusion for intervention. The neurologic scores, infarction and hemorrhage volumes, the expression of Nod-like receptor protein 3, and its downstream targets were analyzed. Hyperbaric oxygen preconditioning decreased both infarction and hemorrhage volumes and improved neurobehavioral function. In addition, hyperbaric oxygen preconditioning provided additional protective effects in hemorrhagic transformation, which was independent of infarction volume. The benefits of hyperbaric oxygen preconditioning on hyperglycemic middle cerebral artery occlusion rats were reversed after blocking the reactive oxygen species/thioredoxin-interacting protein/Nod-like receptor protein 3 pathway. CONCLUSIONS: Nod-like receptor protein 3 inflammasome played an important role in hyperglycemia-enhanced hemorrhagic transformation. Hyperbaric oxygen preconditioning attenuated hemorrhagic transformation through reactive oxygen species/thioredoxin-interacting protein/Nod-like receptor protein 3 pathway.