The AGTR1 gene A1166C polymorphism as a risk factor and outcome predictor of primary intracerebral and aneurysmal subarachnoid hemorrhages

Associations between the angiotensin II type 1 receptor (AGTR1) gene A1166C polymorphism and hypertension, aortic abdominal aneurysms (as a risk factor) as well as cardiovascular disorders (as a risk factor and an outcome predictor) have been demonstrated. We aimed to investigate the role of this polymorphism as risk factors and outcome predictors in primary intracerebral hemorrhage (PICH) and aneurysmal subarachnoid hemorrhage (aSAH). We have prospectively recruited 1078 Polish participants to the study: 261 PICH patients, 392 aSAH patients, and 425 unrelated control subjects. The A1166C AGTR1 gene polymorphism was studied using the tetra-primer ARMS-PCR method. Allele and genotype frequencies were compared with other ethnically different populations. The A1166C polymorphism was not associated with the risk of PICH or aSAH. Among the aSAH patients the AA genotype was associated with a good outcome, defined by a Glasgow Outcome Scale of 4 or 5 (p<0.02). The distribution of A1166C genotypes in our cohort did not differ from other white or other populations of European descent. In conclusion, we found an association between the A1166C AGTR1 polymorphism and outcome of aSAH patients, but not with the risk of PICH or aSAH

Neuromarkers of anxiety and depression in a patient after neuro-ophthalmic surgery of the meningioma - Effect of individually-tailored tDCS and neurofeedback

The aim of the study was to evaluate the effectiveness of individually tailored anodal tDCs/ neurofeedback protocol for the reduction of post-operative depression after a neuroophtalmological operation of the meningioma. The neuromarkers in Quantitative EEG (QEEG) and Event-related potentials (ERPs) were utilized in the construction of protocol and evaluation. Case description. A 45-year-old female after successful neuro-ophthalmic surgery of the meningioma, complained of severe pain and anxiety, difficulties with sleeping, attention and memory problems, as well as inability to continue working in her given profession. Neuropsychological testing showed lack of cognitive disturbances and post-operative depression. Two working hypotheses were tested to find neuromarkers of depression and anxiety. In line with the ‘depression hypothesis’ a frontal alpha asymmetry pattern was found in the patient, and in line with the ‘anxiety’ hypothesis an increased left temporal P1 wave in response to visual stimuli was found in ERPs. A specific alpha asymmetry neurofeedback protocol combined with an anodal tDCS was suggested. Twenty sessions of individually-tailored anodal tDCs/ neurofeedback protocol were performed. The QEEG frontal asymmetry pattern and the excessive temporal P1 wave were normalized after the intervention. Conclusions.The patient recovered from post-operative depression and returned to work after 20 sessions of the combined neurofeedback/tDCS protocol. Specific patterns of QEEG and ERPs serve as neuromarkers for constructing the protocol and for monitoring the results of intervention

Systemic response to rupture of intracranial aneurysms involves expression of specific gene isoforms

Abstract Background Rupture of an intracranial aneurysm (IA) causes a systemic response that involves an immune/inflammatory reaction. Our previous study revealed a downregulation of genes related to T lymphocytes and an upregulation of genes related to monocytes and neutrophils after IA rupture. It remains unknown whether that resulted from alterations in transcription or cell count. We sought to characterize the systemic response to IA rupture through analysis of transcript expression profiles in peripheral blood cells. We also investigated effects of IA rupture on the composition of mononuclear cells in peripheral blood. Methods We included 19 patients in the acute phase of IA rupture (RAA, first 72 h), 20 patients in the chronic phase (RAC, 3–15 months), and 20 controls. Using deep transcriptome sequencing, we analyzed the expression of protein-coding and noncoding RNAs. Expression levels, transcript biotypes, alternative splicing and other features of the regulated transcripts were studied. A functional analysis was performed to determine overrepresented ontological groups among gene expression profiles. Flow cytometry was used to analyze alterations in the level of mononuclear leukocyte subpopulations. Results Comparing RAA and controls, we identified 491 differentially expressed transcripts (303 were downregulated, and 188 were upregulated in RAA). The results indicate that the molecular changes in response to IA rupture occur at the level of individual transcripts. Functional analysis revealed that the most impacted biological processes are related to regulation of lymphocyte activation and toll-like receptor signaling pathway. Differences between RAC and controls were less prominent. Analysis of leukocyte subsets revealed a significantly decreased number of CD4+ lymphocytes and increase of classical and intermediate monocytes in RAA patients compared to controls. Conclusions IA rupture in the acute phase strongly influences the transcription profiles of peripheral blood cells as well as the composition of mononuclear cells. A specific pattern of gene expression alteration was found, suggesting a depression of lymphocyte response and enhancement of monocyte activity

Gene Expression Profiling of Blood in Ruptured Intracranial Aneurysms: in Search of Biomarkers

The molecular mechanisms underlying the systemic response to subarachnoid hemorrhage (SAH) from ruptured intracranial aneurysms (RAs) are not fully understood. We investigated whether the analysis of gene expression in peripheral blood could provide clinically relevant information regarding the biologic consequences of SAH. Transcriptomics were performed using Illumina HumanHT-12v4 microarrays for 43 RA patients and 18 controls (C). Differentially expressed transcripts were analyzed for overrepresented functional groups and blood cell type-specific gene expression. The set of differentially expressed transcripts was validated using quantitative polymerase chain reaction in an independent group of subjects (15 RA patients and 14 C). There were 135 differentially expressed genes (false discovery rate ⩽1%, absolute fold change ⩾1.7): the abundant levels of 78 mRNAs increased and 57 mRNAs decreased. Among RA patients, transcripts specific to T lymphocyte subpopulations were downregulated, whereas those related to monocytes and neutrophils were upregulated. Expression profiles of a set of 16 genes and lymphocyte-to-monocyte-and-neutrophil gene expression ratios distinguished RA patients from C. These results indicate that SAH from RAs strongly influences the transcription profiles of blood cells. A specific pattern of these changes suggests suppression in lymphocyte response and enhancements in monocyte and neutrophil activities. This is probably related to the immunodepression observed in SAH