Conventional surfactant proteins (A, B, C, and D) are important players of the innate immunity in the central nervous system and serve as effective regulators of cerebrospinal fluid rheology, probably being involved in clearance of detrimental metabolites like beta-amyloid and phospho-tau. Recently, a novel surfactant protein, SP-G, was described in kidneys and peripheral endocrine and exocrine glands. So far, its presence and possible functions in the central nervous system are unknown. Therefore, our study aimed to elucidate the presence of SP-G in the brain and its concentration in normal and pathologic samples of cerebrospinal fluid in order to gain first insight into its regulation and possible functions. A total of 121 samples of human cerebrospinal fluid (30 controls, 60 hydrocephalus patients, 7 central nervous system infections, and 24 brain hemorrhage patients) and 21 rat brains were included in our study. CSF samples were quantified using a commercially available ELISA system. Results were analyzed statistically using SPSS 22, performing Spearman Rho correlation and ANOVA with Dunnett's post hoc analysis. Rat brains were investigated via immunofluorescence to determine SP-G presence and colocalization with common markers like aquaporin-4, glial fibrillary acidic protein, platelet endothelial adhesion molecule 1, and neuronal nuclear antigen. SP-G occurs associated with brain vessels, comparable to other conventional SPs, and is present in a set of cortical neurons. SP-G is furthermore actively produced by ependymal and choroid plexus epithelium and secreted into the cerebrospinal fluid. Its concentrations are low in control subjects and patients suffering from aqueductal stenosis, higher in normal pressure hydrocephalus (p < 0.01), and highest in infections of the central nervous system and brain hemorrhage (p < 0.001). Interestingly, SP-G did correlate with total CSF protein in patients with CNS infections and hemorrhage, but not with cell count. Based on the changes in CSF levels of SP-G in hydrocephalus, brain hemorrhage, and CNS infections as well as its abundance at CSF flow-related anatomical structures closely associated with immunological barrier systems, importance for CSF rheology, brain waste clearance, and host defense is assumable. Thus, SP-G is a potential new CSF biomarker, possibly not only reflecting aspects of CNS innate immune responses, but also rheo-dynamically relevant changes of CSF composition, associated with CSF malabsorbtion. However, further studies are warranted to validate our findings and increase insight into the physiological importance of SP-G in the CNS.

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BackgroundThis case report describes a focal brain lesion in an alpaca (Vicugna pacos). Although this is a restricted study based on a single animal, neuropathological features are reported that are most likely attributed to a vascular event with either ischemic or hemorrhagic pathology. Concerning translational issues, these findings extend neurovascular unit concept to the alpacas’ brain and qualify a larger panel of stroke tissue markers for further exploration of ischemic or hemorrhagic consequences beyond the usually used small animal models in stroke research.Case presentationA brain lesion indicative of a stroke was diagnosed in a 3-year-old female alpaca as an incidental finding during a post mortem examination. The rostral portion of the right frontal lobe contained a 1.0 × 1.5 × 1.7 cm lesion that extended immediately to the overlying leptomeninges. Microscopically, it was composed of liquefactive necrosis with cholesterol crystal deposition and associated granulomatous inflammation as well as vascularized fibrous connective tissue rimmed by proliferated astrocytes. Multiple fluorescence labeling of the affected brain regions revealed strong microgliosis as shown by immunostaining of the ionized calcium binding adapter molecule 1 and astrogliosis as demonstrated by enhanced immunoreactivity for glial fibrillary acidic protein. In parallel, a drastic neuronal loss was detected by considerably diminished immunolabeling of neuronal nuclei. Concomitantly, up-regulated immunoreactivities for collagen IV and neurofilament light chains were found in the affected tissues, indicating vascular and cytoskeletal reactions.ConclusionsDriven by these neuropathological features, the incidental brain lesion found in this alpaca strongly suggests an ischemic or hemorrhagic etiology. However, since typical hallmarks became verifiable as previously described for other species affected by focal cerebral ischemia, the lesion is more likely related to an ischemic event. Nevertheless, as such cellular alterations might be difficult to distinguish from other brain lesions as for instance caused by inflammatory processes, adjuvant observations and species-related features need to be considered for etiological interpretations. Indeed, the lack of neurological deficits is likely attributed to the location of the lesion within the rostral aspect of the right frontal lobe of the alpacas’ brain. Further, fibroblast migration from the meninges likely caused the intralesional scar formation.

Introduction: Surfactant proteins (SP) have been shown to be inherent proteins of the human CNS and are altered during acute and chronic disturbances of CSF circulation. Aim of the study was to examine the changes of surfactant protein concentrations in CSF of preterm babies suffering from intraventricular hemorrhage. Patients and Methods: Consecutive CSF samples of 21 preterm infants with intraventricular hemorrhages (IVH) and posthemorrhagic hydrocephalus (PHHC) were collected at primary intervention, after 5-10 days and at time of shunt insertion ∼50 days after hemorrhage. Samples were analyzed for surfactant proteins A, B, C, and G by ELISA assays and the results were compared to 35 hydrocephalus patients (HC) without hemorrhage and 6 newborn control patients. Results and Discussion: Premature patients with IVH showed a significant elevation of surfactant proteins SPA , C, and G compared to HC and control groups: mean values for the respective groups were SPA 4.19 vs. 1.08 vs. 0.38 ng/ml. Mean SP-C 3.63 vs. 1.47 vs. 0.48 ng/ml. Mean SP-G 3.86 vs. 0.17 vs. 0.2 ng/ml. SPA and G concentrations were slowly falling over time without reaching normal values. SP-C levels declined faster following neurosurgical interventions and reached levels comparable to those of hydrocephalus patients without hemorrhage. Conclusion: Intraventricular hemorrhages of premature infants cause posthemorrhagic CSF flow disturbance and are associated with highly significant elevations of surfactant proteins A, C, and G independent of total CSF protein concentrations.

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