Primary head injury is often followed by secondary brain damage. However, the association between injury circumstances and the prevalence of secondary injuries remains unclear. We report the prevalence and association of secondary brain injuries with the circumstances in which a head injury was sustained. The sample comprised 76 neuropathologically examined medico-legal autopsy cases with an acute primary head injury. Neuropathology reports were analysed to determine the prevalence of various secondary injuries, i.e., hypoxic-ischaemic neuronal injury, brain oedema, and vascular axonal injury (VAI). The prevalences were compared between cases from three distinct injury circumstances, i.e., fall, assault, and strangulation. The sample had a median age of 49 years (interquartile range 27-73) and 71.1% were identified as male. As for distinct injury circumstances, the sample comprised 14 fall cases, 21 assault victims, and 6 strangulation victims. The prevalence of hypoxic-ischaemic neuronal injury was highest in strangulations (100.0%), followed by assaults (81.0%) and falls (64.3%); of specific brain regions, statistically significant differences between the three case groups were found in frontal and parietal cortex (p ≤ 0.018) and the hippocampus (p = 0.005). Brain oedema was present in approximately half of assault (47.6%) and strangulation cases (50.0%), contrastingly to the lower prevalence in falls (7.1%; p = 0.024). The prevalence of VAI appeared higher among assault (23.8%) and strangulation cases (16.7%) compared to falls (7.1%), but the differences were not statistically significant. We conclude that hypoxic-ischaemic neuronal injury and brain oedema were more prevalent among assault and strangulation cases compared to falls.

Aim To investigate the correlations between tumour characteristics, symptoms, intraoperative findings, and outcomes in patient with meningioma. Methods A retrospective study was conducted on 86 surgically treated patients at Department of Neurosurgery of Cantonal Hospital Zenica from 2010 to 2020. Patients with intracranial meningiomas underwent neurological evaluation and MRI scans to analyse tumour characteristics, including volume (TV), peritumoral brain oedema (PTBE) and oedema index (EI). Surgical treatment was performed, followed by postoperative MRI and outcome assessment. Intraoperatively, the tumour\'s relationship with cortex, pial membrane, skull bones, and sinuses was evaluated, and the extent of tumour resection was graded. Meningioma samples underwent histopathological analysis to assess the grade and regularity of borders, and Ki-67 labelling index was determined using immunohistochemistry. Results Significant correlations were found between PTBE and Ki67 expression (p<0.001), PTBE and vomiting/nausea (p=0.002), cognitive impairment (p=0.047), venous compression (p=0.001), cortical, pial and dural invasion (p<0.05), and the postoperative presence of oedema (p=0.002). Venous compression, cortical, pial, dural and bone invasion positively correlated with Ki-67 expression (p<0.001). Grade and tumour border positively correlated with Ki-67 expression (p<0.001). Oedema persistence postoperatively showed a positive correlation with Ki-67 expression (p<0.001). Conclusion The study revealed significant correlations between Ki-67 expression and PTBE, with notable associations with clinical symptoms, tumour characteristics, and postoperative oedema presence.

暂无摘要。

Brain oedema is a life-threatening complication of various neurological conditions. Understanding molecular mechanisms of brain volume regulation is critical for therapy development. Unique insight comes from monogenic diseases characterized by chronic brain oedema, of which megalencephalic leukoencephalopathy with subcortical cysts (MLC) is the prototype. Variants in MLC1 or GLIALCAM, encoding proteins involved in astrocyte volume regulation, are the main causes of MLC. In some patients, the genetic cause remains unknown. We performed genetic studies to identify novel gene variants in MLC patients, diagnosed by clinical and MRI features, without MLC1 or GLIALCAM variants. We determined subcellular localization of the related novel proteins in cells and in human brain tissue. We investigated functional consequences of the newly identified variants on volume regulation pathways using cell volume measurements, biochemical analysis and electrophysiology. We identified a novel homozygous variant in AQP4, encoding the water channel aquaporin-4, in two siblings, and two de novo heterozygous variants in GPRC5B, encoding the orphan G protein-coupled receptor GPRC5B, in three unrelated patients. The AQP4 variant disrupts membrane localization and thereby channel function. GPRC5B, like MLC1, GlialCAM and aquaporin-4, is expressed in astrocyte endfeet in human brain. Cell volume regulation is disrupted in GPRC5B patient-derived lymphoblasts. GPRC5B functionally interacts with ion channels involved in astrocyte volume regulation. In conclusion, we identify aquaporin-4 and GPRC5B as old and new players in genetic brain oedema. Our findings shed light on the protein complex involved in astrocyte volume regulation and identify GPRC5B as novel potentially druggable target for treating brain oedema.

To recalculate biological effective dose values (BED) for radio-surgical treatments of acoustic neuroma from a previous study. BEDs values were previously overestimated by only using beam-on times in calculations, so excluding the important beam-off-times (when deoxyribonucleic acid repair continues) which contribute to the overall treatment time. Simple BED estimations using a mono-exponential approximation may not always be appropriate but if used should include overall treatment time.
Time intervals between isocenters were estimated. These were especially important for the Gamma Knife Model 4C cases since manual changes significantly increase overall treatment times. Individual treatment parameters, such as iso-center number, beam-on-time, and beam-off-time, were then used to calculate BED values using a more appropriate bi-exponential model that includes fast and slow components of DNA damage repair over a wider time range.
The revised BED estimates differed significantly from previously published values. The overestimates of BED, obtained using beam-on-time only, varied from 0%-40.3%. BED subclasses, each with a BED range of 5 Gy2.47, indicated that revised values were consistently reduced when compared with originally quoted values, especially for 4C compared with Perfexion cases. Furthermore, subdivision of 4C cases by collimator number further emphasized the impact of scheduled gap times on BED. Further analysis demonstrated important limitations of the mono-exponential model. Target volume was a major confounding factor in the interpretation of the results of this study.
BED values should be estimated by including beam-on and beam-off times. Suggestions are provided for more accurate BED estimations in future studies.

暂无摘要。

In ischaemic stroke, a large reduction in blood supply can lead to the breakdown of the blood brain barrier and to cerebral oedema after reperfusion therapy. Cerebral oedema is marked by elevated intracranial pressure (ICP), tissue herniation and reduced cerebral perfusion pressure. In clinical settings, osmotherapy has been a common practice to decrease ICP. However, there are no guidelines on the choice of administration protocol parameters such as injection doses, infusion time and retention time. Most importantly, the effects of osmotherapy have been proven controversial since the infusion of osmotic agents can lead to a range of side effects. Here, a new Finite Element model of brain oedema and osmotherapy is thus proposed to predict treatment outcome. The model consists of three components that simulate blood perfusion, oedema, and osmotherapy, respectively. In the perfusion model (comprising arteriolar, venous, and capillary blood compartments), an anatomically accurate brain geometry is used to identify regions with a perfusion reduction and potential oedema occurrence in stroke. The oedema model is then used to predict ICP using a porous circulation model with four fluid compartments (arteriolar blood, venular blood, capillary blood, and interstitial fluid). In the osmotherapy model, the osmotic pressure is varied and the changes in ICP during different osmotherapy episodes are quantified. The simulation results of the model show excellent agreement with available clinical data and the model is employed to study osmotherapy under various parameters. Consequently, it is demonstrated how therapeutic strategies can be proposed for patients with different pathological parameters based on simulations.

Brain oedema is a common pathological phenomenon following many diseases and may lead to severe secondary damage. Astrocytes are the most numerous cells in the brain. Five aquaporins (AQPs) have been found in mature astrocytes, which play crucial roles in water transportation. However, most studies have focused on AQP4 or AQP9 and whether another aquaporin such as AQP5 involved in brain oedema is unclear. Here, we addressed the issue that the expression pattern of AQP5 in rat astrocytes in vitro was altered in the hypotonic condition through some mitogen-activated protein kinases (MAPK) pathways. Primary astrocytes were randomly divided into the control group and the hypotonic group. Cell viability was evaluated by MTT test. Immunofluorescence, Western blotting and real-time PCR were used to detect the expression of AQP5. Western blotting was used to detect the variation of MAPK pathway. The present study demonstrated that incubation of astrocytes in the hypotonic medium produced an increase inAQP5 expression, and AQP5 peaked at 6-12 h after hypotension solution exposure. In addition, MAPK pathways were set in motion under hypotension, but not all branches. Only the p38 inhibitor can inhibit AQP5 expression in cultured astrocytes. AQP5 is directly related to the extracellular hypotonic stimuli in astrocytes, which could be regulated through the p38 MAPK pathway.

BACKGROUND: Acute ischaemic stroke (AIS) is caused by significant disturbances in the cerebral bloodflow (CBF) that lead to brain ischaemia and eventually result in irreversible brain tissue damage. The main goal of its treatment is to restore bloodflow to the areas at risk of necrosis. Intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are the mainstay of current therapy, with the latter being widely employed in selected patients with radiologically proven large vessel occlusion (LVO). Despite convincing evidence of its efficacy, up to half of patients undergoing endovascular treatment (EVT) still do not achieve a beneficial functional outcome; this is mainly due to unfavourable brain tissue sequelae. Therefore, factors associated with known adverse brain changes, such as larger infarct size or haemorrhagic and oedematous complications, should be adequately addressed.
OBJECTIVE: To review the available literature describing AIS brain tissue outcome assessed by computed tomography (CT) and/ or magnetic resonance imaging (MRI) in patients undergoing MT treatment. Additionally, to evaluate the association of post-MT tissue changes with short- and long-term prognosis.
METHODS: We searched the PubMed, Scopus, EMBASE, and Google Scholar databases according to established criteria.
RESULTS: We found a total of 264 articles addressing the most common types of AIS tissue sequelae after EVT (i.e. MT with or without IVT as bridging therapy) by brain CT and MRI. These were: follow-up infarct volume (FIV), cerebral oedema (COD) and haemorrhagic transformation (HT). As the next step, 37 articles evaluating factors associated with defined outcomes were selected. Several non-modifiable factors such as age, comorbidities, pretreatment neurological deficit, and collateral circulation status were found to affect stroke tissue sequelae, to varying degrees. Additionally, some factors including time to treatment initiation, selection of treatment device, and periprocedural systemic blood pressure, the modification of which can potentially reduce the occurrence of an unfavourable tissue outcome, were identified. Some recently revealed biochemical and serological parameters may play a similar role.
CONCLUSIONS: The identification of factors that affect post-MT ischaemic area evolution may result in studies assessing the effects of their modification, and potentially improve clinical outcomes. Modifiable parameters, including periprocedural systemic blood pressure and some biochemical factors, may be of particular importance.

UNASSIGNED: Curcumin has a significant effect on cerebral ischaemia-reperfusion injury (CIRI). However, the underlying mechanism is less studied.
UNASSIGNED: This study investigates the role and mechanism of curcumin in CIRI.
UNASSIGNED: CIRI model Sprague-Dawley rats were divided into model, positive control and curcumin low/middle/high dose (50, 100 and 200 mg/kg/d) groups (n = 10 each). Drug intervention was administered by gavage once a day for 4 weeks. We calculated the neurobehavioural score and observed the cerebral infarct volume. Glial cytopathological changes were observed after haematoxylin-eosin staining. Apoptosis was detected by TUNEL (TdT mediated dUTP nick end labelling). Extracellular signal-regulated protein kinase (ERK), C/EBP-homologous protein (CHOP) and caspase-11 mRNA were detected by real-time PCR. Phosphorylated ERK (p-ERK), phosphorylated CHOP (p-CHOP) and caspase-11 were detected by Western blot. Superoxide dismutase (SOD) activity was detected by xanthine oxidation method; malondialdehyde (MDA) content by thiobarbituric acid colorimetry; and, glutathione (GSH) by spectrophotometry.
UNASSIGNED: Compared with control, the neurobehavioural scores, neuronal apoptosis, MDA, IL-1β, IL-18, mRNAs and protein levels of ERK/p-ERK, CHOP/p-CHOP and caspase-11 in model group were significantly higher (p < 0.01). Compared with model, the positive control and medium/high dose curcumin groups were significantly lower (p < 0.01). However, SOD and GSH decreased significantly in model group but increased significantly in positive control and medium/high dose curcumin groups (p < 0.01). Moreover, curcumin significantly alleviated ischaemic state and neuroinflammation (p < 0.01).
UNASSIGNED: Curcumin may alleviate CIRI through ERK-CHOP-caspase-11 pathway. Our results may provide new insights into the pathogenesis of CIRI, and contribute to the development of treatment strategies for CIRI.