Triggering receptor expressed on myeloid cells 2 (TREM2) plays important roles in brain microglial function in neurodegenerative diseases, but the role of TREM2 in the GBM TME has not been examined. Here, we found that TREM2 is highly expressed in myeloid subsets, including macrophages and microglia in human and mouse GBM tumors and that high TREM2 expression correlates with poor prognosis in patients with GBM. TREM2 loss of function in human macrophages and mouse myeloid cells increased interferon-γ–induced immunoactivation, proinflammatory polarization, and tumoricidal capacity. In orthotopic mouse GBM models, mice with chronic and acute Trem2 loss of function exhibited decreased tumor growth and increased survival. Trem2 inhibition reprogrammed myeloid phenotypes and increased programmed cell death protein 1 (PD-1) ⁺ CD8 ⁺ T cells in the TME. Last, Trem2 deficiency enhanced the effectiveness of anti–PD-1 treatment, which may represent a therapeutic strategy for patients with GBM.

OBJECT: The authors present a retrospective cohort study examining complications in patients undergoing surgery for craniosynostosis using both minimally invasive endoscopic and open approaches. METHODS: Over the past 10 years, 295 nonsyndromic patients (140 undergoing endoscopic procedures and 155 undergoing open procedures) and 33 syndromic patients (endoscopic procedures in 10 and open procedures in 23) met the authors’ criteria. Variables analyzed included age at surgery, presence of a preexisting CSF shunt, skin incision method, estimated blood loss, transfusions of packed red blood cells, use of intravenous steroids or tranexamic acid, intraoperative durotomies, procedure length, and length of hospital stay. Complications were classified as either surgically or medically related. RESULTS: In the nonsyndromic endoscopic group, the authors experienced 3 (2.1%) surgical and 5 (3.6%) medical complications. In the nonsyndromic open group, there were 2 (1.3%) surgical and 7 (4.5%) medical complications. Intraoperative durotomies occurred in 5 (3.6%) endoscopic and 12 (7.8%) open cases, were repaired primarily, and did not result in reoperations for CSF leakage. Similar complication rates were seen in syndromic cases. There was no death or permanent morbidity. Additionally, endoscopic procedures were associated with significantly decreased estimated blood loss, transfusions, procedure length, and length of hospital stay compared with open procedures. CONCLUSIONS: Rates of intraoperative durotomies and surgical and medical complications were comparable between endoscopic and open techniques. This is the largest direct comparison to date between endoscopic and open interventions for synostosis, and the results are in agreement with previous series that endoscopic surgery confers distinct advantages over open surgery in appropriate patient populations.

Neuroinflammation has been implicated in the pathophysiology of post-hemorrhagic hydrocephalus (PHH) of prematurity, but no comprehensive analysis of signaling molecules has been performed using human cerebrospinal fluid (CSF). Lumbar CSF levels of key cytokines (IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12, TNF-α, TGF-β1, IFN-γ) and chemokines (XCL-1, CCL-2, CCL-3, CCL-19, CXCL-10, CXCL-11, CXCL-12) were measured using conventional and multiplexed Enzyme-linked Immunosorbent Assays and compared between preterm infants with PHH and those with no known neurological injury. The relationships between individual biomarker levels and specific CSF cell counts were examined. Total protein (TP) CSF levels were elevated in the PHH subjects compared to controls. CSF levels of IL-1α, IL-4, IL-6, IL-12, TNF-α, CCL-3, CCL-19, and CXCL-10 were significantly increased in PHH whereas XCL-1 was significantly decreased in PHH. When normalizing by TP, IL-1α, IL-1β, IL-10, IL-12, CCL-3, and CCL-19 levels were significantly elevated compared to controls, while XCL-1 levels remained significantly decreased. Among those with significantly different levels in both absolute and normalized levels, only absolute CCL-19 levels showed a significant correlation with CSF nucleated cells, neutrophils, and lymphocytes. IL-1β and CXCL-10 also were correlated with total cell count, nucleated cells, red blood cells, and neutrophils. Neuroinflammation is likely to be an important process in the pathophysiology of PHH. To our knowledge, this is the first study to investigate CSF levels of chemokines in PHH as well as the only one to show XCL-1 selectively decreased in a diseased state. Additionally, CCL-19 was the only analyte studied that showed significant differences between groups and had significant correlation with cell count analysis. The selectivity of CCL-19 and XCL-1 should be further investigated. Future studies will further delineate the role of these cytokines and chemokines in PHH.

Background This study examines relationships between neonatal white and gray matter microstructure and neurodevelopment in very preterm (VPT) infants (≤30 weeks gestation) with high-grade brain injury (BI). Methods Term-equivalent diffusion tensor magnetic resonance imaging data were obtained in 32 VPT infants with high-grade BI spanning grade III/IV intraventricular hemorrhage, post-hemorrhagic hydrocephalus (PHH), and cystic periventricular leukomalacia (BI group); 69 VPT infants without high-grade injury (VPT group); and 55 term-born infants. The Bayley-III assessed neurodevelopmental outcomes at age 2 years. Results BI infants had lower fractional anisotropy (FA) in the posterior limb of the internal capsule (PLIC), cingulum, and corpus callosum, and higher mean diffusivity (MD) in the optic radiations and cingulum than VPT infants. PHH was associated with higher MD in the optic radiations and left PLIC, and higher FA in the right caudate. For BI infants, higher MD in the right optic radiation and lower FA in the right cingulum, PLIC, and corpus callosum were related to motor impairments. Conclusions BI infants demonstrated altered white and gray matter microstructure in regions affected by injury in a manner dependent upon injury type. PHH infants demonstrated the greatest impairments. Aberrant white matter microstructure was related to motor impairment in BI infants.