Lymphocytes infiltrate the stroke core and penumbra and often exacerbate cellular injury. B cells, however, are lymphocytes that do not contribute to acute pathology but can support recovery. B cell adoptive transfer to mice reduced infarct volumes 3 and 7 d after transient middle cerebral artery occlusion (tMCAo), independent of changing immune populations in recipient mice. Testing a direct neurotrophic effect, B cells cocultured with mixed cortical cells protected neurons and maintained dendritic arborization after oxygen-glucose deprivation. Whole-brain volumetric serial two-photon tomography (STPT) and a custom-developed image analysis pipeline visualized and quantified poststroke B cell diapedesis throughout the brain, including remote areas supporting functional recovery. Stroke induced significant bilateral B cell diapedesis into remote brain regions regulating motor and cognitive functions and neurogenesis (e.g., dentate gyrus, hypothalamus, olfactory areas, cerebellum) in the whole-brain datasets. To confirm a mechanistic role for B cells in functional recovery, rituximab was given to human CD20+(hCD20+) transgenic mice to continuously deplete hCD20+-expressing B cells following tMCAo. These mice experienced delayed motor recovery, impaired spatial memory, and increased anxiety through 8 wk poststroke compared to wild type (WT) littermates also receiving rituximab. B cell depletion reduced stroke-induced hippocampal neurogenesis and cell survival. Thus, B cell diapedesis occurred in areas remote to the infarct that mediated motor and cognitive recovery. Understanding the role of B cells in neuronal health and disease-based plasticity is critical for developing effective immune-based therapies for protection against diseases that involve recruitment of peripheral immune cells into the injured brain.
Background: Intramedullary melanocytomas are exceedingly rare and their management is largely based on case reports and small clinical series. They have characteristic imaging and histologic findings that can aid in their diagnosis. Genetic testing may be required for definitive diagnosis and management guidance in ambiguous cases. Case Description: We present the case of a thoracic intramedullary meningeal melanocytoma in a patient unable to undergo an MRI. Conclusion: This is the first reported S-100-negative case with genetic testing to support the diagnosis of a rare intramedullary melanocytoma.
Previous data show that voluntary exercise prior to stroke reduces neuronal injury in wild type (WT) mice. Our lab found that exercise specifically modulates B cells to upregulate IL10, which could reduce post-stroke inflammation. To determine the influence of IL10 on exercise-mediated neuroprotection, IL-10-null mice (male, 12-16 weeks old) were randomly separated into sedentary and voluntary exercise (3 weeks on monitored running wheels) groups. Both groups were subjected to a 60 minute transient middle cerebral artery occlusion, with infarct volumes and splenic immune populations assessed 24 hours after stroke by a blinded observer. Voluntary exercise (n=11) did not reduce infarct volume compared to sedentary mice (n=8) in the absence of IL-10. Exercise increased B2 cell (CD1d-CD5-; p<0.05) and B regulatory (Breg) cell (CD1d+CD5+; p=0.08) populations in the spleen. Mice with the highest exercise intensity exhibited both the lowest splenic Breg populations (p<0.05) and the lowest infarct volumes (p=0.09). This would suggest an IL10-independent mobilization of Bregs by exercise prior to stroke, though future studies should determine if this neuroprotective Breg population moves into the ischemic brain to reduce neuronal injury.
Background: Increasing evidence shows a link between the central nervous system and the immune system in mediating damage, as well as regeneration and repair, following stroke, though most studies focus on T-cell-mediated pathology. While previous work links the B-cell secretion of IL-10 with acute neuroprotection following experimental stroke (PMID: 24374817), the role of B cells in long-term functional recovery is unknown. Hypothesis: The purpose of this study was to assess the protective role of B-cells in improving post-stroke motor function in B-cell deficient mice. Materials and Methods: Adult male transgenic mice expressing human CD20+ (hCD20+) or wild-type (WT) littermate controls (PMID: 17709552) were trained on rotorod for a 2 week duration. Following training, all mice were administered Rituximab (50g ip; PMID: 21359213) daily for 3 days and weekly thereafter. Stroke was induced by a 60-min transient middle cerebral artery occlusion (tMCAo). Post-stroke functional recovery was evaluated 2, 4, 7 and 14 days post-tMCAo. Lymphocytes were isolated from spleen 2 weeks post-tMCAo, stained with antibodies, profiled on a FACS Canto flow cytometer, and analyzed with FlowJo. Results: WT mice recovered to near pre-stroke rotorod performance by 4 days post-tMCAo. In contrast, hCD20+ mice exhibited deficits through 7 days (p<0.05). We confirmed that Rituximab depleted CD20+ B-cells (p<0.05) in the spleen of hCD20+ mice. This post-stroke B-cell depletion reduced CD45+ (p<0.0001) populations, as well as pro-inflammatory CD11b+ macrophage populations (p<0.01). Overall, B-cell depletion increased splenic T-cell percent representation (p<0.001), while decreasing monocyte (p<0.0005) and macrophage (p<0.0001) representation. Conclusions: B-cell depletion in hCD20+ mice prolonged motor deficits in rotorod performance beyond WT mice. B-cell depletion also enhanced a post-stroke immunosuppression of splenic immune cell populations. These data suggest a potential role for B-cells as a therapeutic tool to enhance functional recovery, and counter potentially detrimental post-stroke immunosuppression that contributes to comorbidity during recovery.
Background: Moyamoya (MM) is an uncommon cerebrovascular disease characterized by bilateral, progressive stenosis and occlusion at the terminal portion of the internal carotid arteries around the circle of Willis. MM has a higher prevalence in East Asian population; however, an increasing number of cases of MM are being reported in the US and may reflect a different entity often termed moyamoya syndrome (MMS). A study from 2005 to 2008, reported a 4-fold increase in the prevalence of MM in the US. In this study, we sought to describe the clinical features of patients diagnosed with MMS in a unique, primarily Caucasian Southern US population. Materials and Methods: We performed a retrospective chart review of patients evaluated at our institution from August 2012 to December 2018. Data collected included age, sex, ethnicity, comorbid medical conditions, and laboratory values. Results: Seventy-seven patients with MM were included (52 female and 25 male), average age at time of diagnosis was 42 for females and 48 for males. 81% were Caucasian while 17% were African American, and 3% were Asian. Hypertension was the most common comorbidity affecting these individuals (60%), with hyperlipidemia being the second most common (36%). Autoimmune disorders affected about 22% of this population. The average BMI of females and males was 35 and 29, respectively. Lipid analysis showed similarity in profiles between males and females, and no significant trends were appreciated respective to BMI and age. Interestingly, 85% of individuals had an elevation of sedimentation rate (ESR), Factor VIII, or C - reactive protein (CRP) at the time of diagnosis. Conclusions: Women are affected in a 2:1 ratio as compared to men; which is a consistent trend reported in other studies. Hypertension remains the most common comorbidity affecting these individuals. Though the etiology of MMS remains unclear, various autoimmune disorders have been reported in small case series. While ESR, factor VIII activity, and CRP are non-specific markers of inflammation, the high prevalence of these markers in this population further support an autoimmune or immunological component in MM. Additional prospective studies are needed to further elucidate this relationship.
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