Microglia activation,classification and microglia-mediated neuroinflammatory modulators in subarachnoid hemorrhage

Subarachnoid hemorrhage is a devastating disease with significant mortality and morbidity,despite advances in treating cerebral aneurysms.There has been recent progress in the intensive care management and monitoring of patients with subarachnoid hemorrhage,but the results remain unsatisfactory.Microglia,the resident immune cells of the brain,are increasingly recognized as playing a significant role in neurological diseases,including subarachnoid hemorrhage.In early brain injury following subarachnoid hemorrhage,microglial activation and neuroinflammation have been implicated in the development of disease complications and recovery.To understand the disease processes following subarachnoid hemorrhage,it is important to focus on the modulators of microglial activation and the pro-inflammatory/anti-inflammatory cytokines and chemokines.In this review,we summarize research on the modulators of microglia-mediated inflammation in subarachnoid hemorrhage,including transcriptome changes and the neuroinflammatory signaling pathways.We also describe the latest developments in single-cell transcriptomics for microglia and summarize advances that have been made in the transcriptome-based classification of microglia and the implications for microglial activation and neuroinflammation.

Microglia accumulation and activation after subarachnoid hemorrhage

Subarachnoid hemorrhage(SAH) is a severe cerebrovascular disease accounting for a significant portion of young patients with stroke with high morbidity and mortality(van Gijn et al., 2007). Secondary brain injury resulting from neuroinflammation is considered to be a key pathological process(Zheng and Wong, 2017). Microglia, the resident immune cells of the brain, are implicated in numerous neurological diseases, such as Alzheimer's disease。

Phase Ⅰ/Ⅱ randomized controlled trial of autologous bone marrow-derived mesenchymal stem cell therapy for chronic stroke

AIM To examine the safety and efficacy of mesenchymal stem cell(MSC) therapy for intracerebral haemorrhage with neurological dysfunctions for a year.METHODS MSC were ex vivo expanded from 29 mL(17-42 mL) autologous bone marrow. Patients were randomized to have two intravenous injections of autologous MSC or placebos in four weeks apart. Neurological functions and clinical outcomes were monitored before treatment and at 12^(th), 16^(th), 24^(th), 36^(th) and 60^(th) week upon completion of^(th)e treatment. RESULTS A mean of 4.57 × 10~7(range: 1.43 × 10~7-8.40 × 10~7) MSC per infusion was administered accounting to 8.54 × 10~5(2.65 × 10~5-1.45 × 10~6) per kilogram body weight in two occasions. There was neither adverse event at time of administration nor sign of de novo tumour development among patients after monitoring for a year post MSC therapy. Neuro-restoration and clinical improvement in terms of modified Barthel index, functional independence measure and extended Glasgow Outcome Scale were evident among patients having MSC therapy compared to patients receiving placebos. CONCLUSION Intravenous administration of autologous bone marrowderived MSC is safe and has the potential of improving neurological functions in chronic stroke patients with severe disability.

ABC/2 formula for"bedside"postoperative pneumocephalus volume measurement

Background:Postoperative pneumocephalus is associated with a higher risk of recurrence of chronic subdural hematoma(cSDH).However,there is no verified simple way to measure the pneumocephalus volume at the bedside for daily clinical use.The ABC/2 method was shown to be a simple and reliable technique to estimate volumes of intracranial lesions,such as intracranial hematomas.This study aims to evaluate the accuracy of the ABC/2 formula in estimating volumes of pneumocephalus,as compared to the gold standard with computer-assisted volumetric analysis.Methods:A total of 141 postoperative computed tomographic(CT)brain scans of cSDH patients with burr-hole drainage were analysed.Pneumocephalus volume was measured independently by both the ABC/2 formula and the computer-assisted volumetric measurement.For the computer-assisted measurement,the volume of the air was semiautomatically segmented and calculated by computer software.Linear regression was used to determine the correlation between the ABC/2 method and computer-assisted measurement.Results:The postoperative pneumocephalus volume after bilateral burr-hole drainage was significantly larger than that of unilateral burr-hole drainage(29.34 ml versus 12.21 ml,p<0.001).The estimated volumes by the formula ABC/2 significantly correlated to the volumes as measured by the computer-assisted volumetric technique,with r=0.992(p<0.001).The Pearson correlation coefficient is very close to 1,which signifies a very strong positive correlation,and it is statistically significant.Conclusions:An excellent correlation is observed between the ABC/2 method and the computer-assisted measurement.This study verified that the ABC/2 method is an accurate and simple"bedside"technique to estimate pneumocephalus volume.

Chronic subdural haematoma during the COVID-19 lockdown period:late presentation with a longer interval from the initial head injury to the final presentation and diagnosis

Background:The COVID-19 novel coronavirus is contagious,and the mortality is higher in the elderly population.Lockdown in different parts of the world has been imposed since January 2020.Chronic subdural haematoma (cSDH) has a unique natural history in which symptoms can be non-specific,and the onset is insidious.This study aims to evaluate the impact of the COVID-19 pandemic on the presentation of cSDH.Methods:Consecutive adult cSDH patients admitted from 1 March 2020 to 30 April 2020 were reviewed.Exclusion criteria including those who had no definite history of head injury or the diagnosis of cSDH were made from a scheduled follow-up scan.Corresponding data during the same period in 2019 were reviewed for comparison.The primary outcome was the interval between the initial head injury and the final radiological diagnosis of cSDH.Secondary outcomes include Markwalder chronic subdural haematoma grade upon admission,length of stay in the acute hospital,and the modified Rankin scale (mRS) upon discharge.Results:For the primary outcome,the average interval between head injury and the diagnosis of cSDH was significantly longer at 56.6 days (49 to 74 days,SD 9.83 days) during the period from March to April 2020,versus 29.4 days (17 to 42 days,SD 8.59 days) in 2019 for the corresponding period (p = 0.00703).There was no significant difference in the functional outcome upon discharge.Conclusions:cSDH patients can present late during the COVID-19 lockdown period.The functional outcome was comparable when operations for drainage were timely performed.