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1.
Front Neurol ; 15: 1413904, 2024.
Article in English | MEDLINE | ID: mdl-39099781

ABSTRACT

Introduction: Brain edema is a life-threatening complication that occurs after glioma surgery. There are no noninvasive and specific treatment methods for brain edema. Hydrogen is an anti-inflammatory and antioxidant gas that has demonstrated therapeutic and preventative effects on several diseases, particularly in the nervous system. This study aimed to determine the therapeutic effects of hydrogen administration on brain edema following glioma surgery and elucidate its mechanism. Methods: A single-center, randomized controlled clinical trial of hydrogen inhalation was conducted (China Clinical Trial Registry [ChiCTR-2300074362]). Participants in hydrogen (H) group that inhaled hydrogen experienced quicker alleviation of postoperative brain edema compared with participants in control (C) group that inhaled oxygen. Results: The volume of brain edema before discharge was significantly lower in the H group (p < 0.05). Additionally, the regression rate of brain edema was higher in the H group than in the C group, which was statistically significant (p < 0.05). Furthermore, 3 days after surgery, the H group had longer total sleep duration, improved sleep efficiency, shorter sleep latency, and lower numerical rating scale (NRS) scores (p < 0.05). Discussion: In conclusion, hydrogen/oxygen inhalation effectively reduced postoperative brain edema in glioma patients. Further research is necessary to understand the underlying mechanisms of hydrogen's therapeutic effects. Hydrogen is expected to become a new target for future adjuvant therapy for brain edema.

2.
Neurocrit Care ; 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39117964

ABSTRACT

BACKGROUND: This study aims to investigate the efficacy and safety of glibenclamide treatment in patients with acute aneurysmal subarachnoid hemorrhage (aSAH). METHODS: The randomized controlled trial was conducted from October 2021 to May 2023 at two university-affiliated hospitals in Beijing, China. The study included patients with aSAH within 48 h of onset, of whom were divided into the intervention group and the control group according to the random number table method. Patients in the intervention group received glibenclamide tablet 3.75 mg/day for 7 days. The primary end points were the levels of serum neuron-specific enolase (NSE) and soluble protein 100B (S100B) between the two groups. Secondary end points included evaluating changes in the midline shift and the gray matter-white matter ratio, as well as assessing the modified Rankin Scale scores during follow-up. The trial was registered at ClinicalTrials.gov (identifier NCT05137678). RESULTS: A total of 111 study participants completed the study. The median age was 55 years, and 52% were women. The mean admission Glasgow Coma Scale was 10, and 58% of the Hunt-Hess grades were no less than grade III. The baseline characteristics of the two groups were similar. On days 3 and 7, there were no statistically significant differences observed in serum NSE and S100B levels between the two groups (P > 0.05). The computer tomography (CT) values of gray matter and white matter in the basal ganglia were low on admission, indicating early brain edema. However, there were no significant differences found in midline shift and gray matter-white matter ratio (P > 0.05) between the two groups. More than half of the patients had a beneficial outcome (modified Rankin Scale scores 0-2), and there were no statistically significant differences between the two groups. The incidence of hypoglycemia in the two groups were 4% and 9%, respectively (P = 0.439). CONCLUSIONS: Treating patients with early aSAH with oral glibenclamide did not decrease levels of serum NSE and S100B and did not improve the poor 90-day neurological outcome. In the intervention group, there was a visible decreasing trend in cases of delayed cerebral ischemia, but no statistically significant difference was observed. The incidence of hypoglycemia did not differ significantly between the two groups.

3.
Neurocrit Care ; 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39138715

ABSTRACT

Traumatic brain injury leads to glutamate release, which overstimulates N-methyl-D-aspartate (NMDA) receptors, leading to neurotoxicity and cytotoxic edema. NMDA receptor antagonists may offer neuroprotection by blocking this pathway. The objective of this systematic review is to assess the efficacy of NMDA receptor antagonists for traumatic brain injury-induced brain edema in rodent models. This systematic review followed Cochrane Handbook guidelines and registered its protocol in PROSPERO (ID: CRD42023440934). Here, we included controlled rodent animal models comparing NMDA antagonist use with a placebo treatment. Outcome measures included the reduction of cerebral edema, Neurobehavioral Severity Scale, and adverse effects. The search strategy used Medical Subject Headings terms related to traumatic brain injury and NMDA receptor antagonists. The Collaborative Approach to Meta Analysis and Review of Animal Experimental Studies (CAMARADES) checklist and Systematic Review Centre for Laboratory Animal Experimentation's (SYRCLE's) tools were used to measure the quality and bias of included studies. The synthesis of results was presented in a meta-analysis of standard mean difference. Sixteen studies were included, with the predominant drugs being ifenprodil, MK-801, magnesium, and HU-211. The subjects consisted of Sprague-Dawley or Sabra rats. The analysis showed a significant reduction in brain edema with NMDA antagonist treatment (Standardized mean difference [SMD] - 1.17, 95% confidence interval [CI] - 1.59 to - 0.74, p < 0.01), despite high heterogeneity (I2 = 72%). Neurobehavioral Severity Scale also significantly improved (mean difference - 3.32, 95% CI - 4.36 to - 2.28, p < 0.01) in animals receiving NMDA antagonists. Administration within 1 h after injury showed a modest enhancement in reducing brain edema compared with the baseline (SMD - 1.23, 95% CI - 1.69 to - 0.77, p < 0.01). Studies met standards for animal welfare and model appropriateness. Although baseline comparability and selective reporting bias were generally addressed, key biases such as randomization, allocation concealment, and blinding were often unreported. Overall, NMDA antagonists exhibit promising efficacy in the treatment of traumatic brain injury. Notably, our systematic review consistently demonstrated a significant reduction in brain edema with compounds including HU-211 and NPS 150.

4.
Clin Case Rep ; 12(8): e9100, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39091616

ABSTRACT

Key Clinical Message: Posterior Reversible Encephalopathy Syndrome, typically characterized by parieto-occipital vasogenic edema, can present atypically, as a bilateral symmetrical vasogenic edema in the basal ganglia, featuring the called "lentiform fork sign." Prompt recognition of such variations is crucial for accurate diagnosis and tailored management, highlighting the complexity of this syndrome's manifestations. Abstract: Posterior Reversible Encephalopathy Syndrome (PRES) manifests as transient neurological symptoms and cerebral edema, commonly associated with immunosuppressive drugs (ISDs) in transplant recipients. ISDs can lead to endothelial dysfunction and compromise the blood-brain barrier. Typically, PRES exhibits identifiable MRI patterns, often demonstrating vasogenic edema in the bilateral parieto-occipital white matter. Identifying unique presentations, such as the recently observed "lentiform fork sign," commonly seen in uremic encephalopathy, emphasizes this syndrome's broad spectrum manifestations. A 19-year-old male, who underwent bilateral lung and liver transplantation, experienced a bilateral tonic-clonic seizure of unknown onset 47 days post-surgery. MRI findings revealed an unconventional PRES pattern, featuring the "lentiform fork sign" as bilateral symmetrical vasogenic edema in the basal ganglia, surrounded by a hyperintense rim outlining the lentiform nucleus bilaterally. Subsequent management, including ISD modification and magnesium supplementation, resulted in clinical and neuroimaging resolution. An almost complete clinical and radiological resolution was achieved after 14 days. The occurrence of PRES in transplant recipients highlights the intricate interplay among ISDs, physiological factors, and cerebrovascular dynamics, potentially involving direct neurovascular endothelial toxicity and disruption of the blood-brain barrier. Neuroimaging plays a pivotal role in diagnosis. The distinctive "lentiform fork sign" was observed in this patient despite the absence of typical metabolic disturbances. Management strategies usually involve reducing hypertension, discontinuing ISDs, correcting electrolyte imbalances, and initiating antiseizure drugs if necessary. Identifying the presence of the "lentiform fork sign" alongside typical PRES edema in a patient lacking renal failure emphasizes that this manifestation is not solely indicative of uremic encephalopathy. Instead, it might represent the final common pathway resulting from alterations in the blood-brain barrier integrity within the deep white matter. Understanding such atypical imaging manifestations could significantly aid earlier and more precise diagnosis, influencing appropriate management decisions.

5.
JIMD Rep ; 65(4): 212-225, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38974613

ABSTRACT

Background: NAXE-encephalopathy or early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-1 (PEBEL-1) and NAXD-encephalopathy (PEBEL-2) have been described recently as mitochondrial disorders causing psychomotor regression, hypotonia, ataxia, quadriparesis, ophthalmoparesis, respiratory insufficiency, encephalopathy, and seizures with the onset being usually within the first three years of life. It usually leads to rapid disease progression and death in early childhood. Anecdotal reports suggest that niacin, through its role in nicotinamide adenine dinucleotinde (NAD) de novo synthesis, corrects biochemical derangement, and slows down disease progression. Reports so far have supported this observation. Methods: We describe a patient with a confirmed PEBEL-1 diagnosis and report his clinical response to niacin therapy. Moreover, we systematically searched the literature for PEBEL-1 and PEBEL-2 patients treated with niacin and details about response to treatment and clinical data were reviewed. Furthermore, we are describing off-label use of a COX2 inhibitor to treat niacin-related urticaria in NAXE-encephalopathy. Results: So far, seven patients with PEBEL-1 and PEBEL-2 treated with niacin were reported, and all patients showed a good response for therapy or stabilization of symptoms. We report a patient exhibiting PEBEL-1 with an unfavorable outcome despite showing initial stabilization and receiving the highest dose of niacin reported to date. Niacin therapy failed to halt disease progression or attain stabilization of the disease in this patient. Conclusion: Despite previous positive results for niacin supplementation in patients with PEBEL-1 and PEBEL-2, this is the first report of a patient with PEBEL-1 who deteriorated to fatal outcome despite being started on the highest dose of niacin therapy reported to date.

6.
J Inherit Metab Dis ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38994653

ABSTRACT

Citrin deficiency (CD) is a complex metabolic condition due to defects in SLC25A13 encoding citrin, an aspartate/glutamate carrier located in the mitochondrial inner membrane. The condition was first described in Japan and other East Asian countries in patients who were thought to suffer from classical citrullinemia type 1, and was therefore classified as a urea cycle disorder. With an improved understanding of its molecular basis, it became apparent that a defect of citrin is primarily affecting the malate-aspartate shuttle with however multiple secondary effects on many central metabolic pathways including glycolysis, gluconeogenesis, de novo lipogenesis and ureagenesis. In the meantime, it became also clear that CD must be considered as a global disease with patients identified in many parts of the world and affected by SLC25A13 genotypes different from those known in East Asian populations. The present short review summarizes the (hi)story of this complex metabolic condition and tries to explain the relevance of including CD as a differential diagnosis in neonates and infants with cholestasis and in (not only adult) patients with hyperammonemia of unknown origin with subsequent impact on the emergency management.

7.
Curr Neurovasc Res ; 20(5): 535-543, 2024.
Article in English | MEDLINE | ID: mdl-39004958

ABSTRACT

AIMS: To investigate the factors of postoperative malignant brain edema (MBE) in patients with acute ischemic stroke (AIS) treated with endovascular treatment (EVT). BACKGROUND: MBE is a severe complication following EVT for AIS, and it is essential to identify risk factors early. Peripheral arterial lactate (PAL) levels may serve as a potential predictive marker for MBE. OBJECTIVE: To determine whether immediate postoperative PAL levels and the highest PAL level within 24 hours of EVT are independently associated with MBE development in AIS patients. METHODS: We retrospectively analyzed patients with AIS who underwent EVT from October 2019 to October 2022. Arterial blood was collected every 8 h after EVT to measure PAL, and record the immediate postoperative PAL and the highest PAL level within 24 h. Brain edema was evaluated using brain computed tomography scans within 7 days of EVT. RESULTS: The study included 227 patients with a median age of 71 years, of whom 59.5% were male and MBE developed in 25.6% of patients (58/227). Multivariate logistic regression analysis showed that the immediate postoperative PAL (odds ratio, 1.809 [95% confidence interval (CI), 1.215-2.693]; p = 0.004) and the highest PAL level within 24 h of EVT (odds ratio, 2.259 [95% CI, 1.407-3.629]; p = 0.001) were independently associated with MBE. The area under the curve for predicting MBE based on the highest PAL level within 24 hours of EVT was 0.780 (95% CI, 0.711-0.849). CONCLUSION: Early increase in PAL levels is an independent predictor of MBE after EVT in AIS patients.


Subject(s)
Brain Edema , Endovascular Procedures , Ischemic Stroke , Lactic Acid , Humans , Male , Female , Brain Edema/etiology , Brain Edema/blood , Brain Edema/diagnostic imaging , Aged , Retrospective Studies , Endovascular Procedures/adverse effects , Endovascular Procedures/methods , Middle Aged , Ischemic Stroke/blood , Ischemic Stroke/surgery , Lactic Acid/blood , Aged, 80 and over , Postoperative Complications/blood , Postoperative Complications/etiology , Postoperative Complications/diagnostic imaging
8.
Neuropharmacology ; 257: 110054, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38950691

ABSTRACT

Vasogenic brain edema, a potentially life-threatening consequence following an acute ischemic stroke, is a major clinical problem. This research aims to explore the therapeutic benefits of nimodipine, a calcium channel blocker, in mitigating vasogenic cerebral edema and preserving blood-brain barrier (BBB) function in an ischemic stroke rat model. In this research, animals underwent the induction of ischemic stroke via a 60-min blockage of the middle cerebral artery and treated with a nonhypotensive dose of nimodipine (1 mg/kg/day) for a duration of five days. The wet/dry method was employed to identify cerebral edema, and the Evans blue dye extravasation technique was used to assess the permeability of the BBB. Furthermore, immunofluorescence staining was utilized to assess the protein expression levels of matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1). The study also examined mitochondrial function by evaluating mitochondrial swelling, succinate dehydrogenase (SDH) activity, the collapse of mitochondrial membrane potential (MMP), and the generation of reactive oxygen species (ROS). Post-stroke administration of nimodipine led to a significant decrease in cerebral edema and maintained the integrity of the BBB. The protective effects observed were associated with a reduction in cell apoptosis as well as decreased expression of MMP-9 and ICAM-1. Furthermore, nimodipine was observed to reduce mitochondrial swelling and ROS levels while simultaneously restoring MMP and SDH activity. These results suggest that nimodipine may reduce cerebral edema and BBB breakdown caused by ischemia/reperfusion. This effect is potentially mediated through the reduction of MMP-9 and ICAM-1 levels and the enhancement of mitochondrial function.


Subject(s)
Blood-Brain Barrier , Brain Edema , Calcium Channel Blockers , Ischemic Stroke , Matrix Metalloproteinase 9 , Nimodipine , Animals , Nimodipine/pharmacology , Brain Edema/drug therapy , Brain Edema/etiology , Brain Edema/metabolism , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/metabolism , Male , Rats , Ischemic Stroke/drug therapy , Ischemic Stroke/metabolism , Matrix Metalloproteinase 9/metabolism , Calcium Channel Blockers/pharmacology , Disease Models, Animal , Reactive Oxygen Species/metabolism , Membrane Potential, Mitochondrial/drug effects , Rats, Sprague-Dawley , Intercellular Adhesion Molecule-1/metabolism , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/complications , Mitochondrial Swelling/drug effects , Succinate Dehydrogenase/metabolism
9.
Acta Neurochir (Wien) ; 166(1): 286, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38980438

ABSTRACT

BACKGROUND: Intraventricular meningioma (IVM) is a rare subtype of intracranial meningioma, accounting for 9.8 to 14% of all intraventricular tumors. Currently, there is no clear consensus on which patients with IVM should receive conservative treatment, surgery, or stereotactic radiosurgery (SRS). This research aims to analyze the outcomes, including survival and recurrence rates of patients who undergo SRS for IVM as a primary or adjuvant treatment. METHODS: A systematic search was conducted in Scopus, Web of Science, PubMed, and Embase till June 5th 2023. Screening and data extraction were performed by two independent authors. Random-effect meta-analysis was performed to determine the tumor control proportion of IVM cases treated with SRS. Individual patient data (IPD) meta-analysis was performed for the progression-free survival (PFS) of the patients in the follow-up time. All analyses were performed using the R programming language. RESULTS: Out of the overall 132 records, 14 were included in our study, of which only 7 had enough data for the meta-analysis. The tumor control proportion was 0.92 (95% CI, 0.69-0.98) in patients who underwent SRS for primary IVM. The overall tumor control in both primary and adjuvant cases was 0.87 (95% CI, 0.34-0.99). the heterogeneity was not significant in both meta-analyses (P = 0.73 and P = 0.92, respectively). Post-SRS perifocal edema occurred in 16 out of 71 cases (0.16; 95% CI, 0.03-0.56), with no significant heterogeneity (P = 0.32). IPD meta-analysis showed a PFS of 94.70% in a 2-year follow-up. Log-rank test showed better PFS in primary SRS compared to adjuvant SRS (P < 0.01). CONCLUSIONS: According to this study, patients with IVM can achieve high rates of tumor control with a low risk of complications when treated with SRS, regardless of whether they have received prior treatment. Although SRS could be a promising first-line treatment option for asymptomatic IVM, its efficacy in symptomatic patients and its comparison with resection require further investigation.


Subject(s)
Meningeal Neoplasms , Meningioma , Radiosurgery , Humans , Meningioma/surgery , Meningioma/pathology , Radiosurgery/methods , Meningeal Neoplasms/surgery , Meningeal Neoplasms/radiotherapy , Cerebral Ventricle Neoplasms/surgery , Treatment Outcome
10.
Front Med (Lausanne) ; 11: 1422040, 2024.
Article in English | MEDLINE | ID: mdl-39040896

ABSTRACT

Objective: Globally, many societies are experiencing an increase in the number of older adults (>65 years). However, there has been a widening gap between the chronological and biological age of older adults which trend to a more active and social participating part of the society. Concurrently, the incidence of traumatic brain injury (TBI) is increasing globally. The aim of this study was to investigate the outcome after TBI and decompressive craniectomy (DC) in older adults compared with younger patients. Methods: A retrospective, multi-centre, descriptive, observational study was conducted, including severe TBI patients who were treated with DC between 2005 and 2022. Outcome after discharge and 12 months was evaluated according to the Glasgow Outcome Scale (Sliding dichotomy based on three prognostic bands). Significance was established as p ≤ 0.05. Results: A total of 223 patients were included. The majority (N = 158, 70.9%) survived TBI and DC at discharge. However, unfavourable outcome was predominant at discharge (88%) and after 12 months (67%). There was a difference in favour of younger patients (≤65 years) between the age groups at discharge (p = 0.006) and at 12 months (p < 0.001). A subgroup analysis of the older patients (66 to ≤74 vs. ≥75 years) did not reveal any significant differences. After 12 months, 64% of the older patients had a fatal outcome. Only 10% of those >65 years old had a good or very good outcome. 25% were depending on support in everyday activities. After 12 months, the age (OR 0.937, p = 0.007, CI 95%: 0.894-0.981; univariate) and performed cranioplasty (univariate and multivariate results) were influential factors for the dichotomized GOS. For unfavourable outcome after 12 months, the thresholds were calculated for age = 55.5 years (p < 0.001), time between trauma and surgery = 8.25 h (p = 0.671) and Glasgow Coma Scale (GCS) = 4 (p = 0.429). Conclusion: Even under the current modern conditions of neuro-critical care, with significant advances in intensive care and rehabilitation medicine, the majority of patients >65 years of age following severe TBI and DC died or were dependent and usually required extensive support. This aspect should also be taken into account during decision making and counselling (inter-, intradisciplinary or with relatives) for a very mobile and active older section of society, together with the patient's will.

11.
Fitoterapia ; 177: 106098, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38950636

ABSTRACT

Brain edema after ischemic stroke could worsen cerebral injury in patients who received intravenous thrombolysis. Cornus officinalis Sieb. et Zucc., a long-established traditional Chinese medicine, is beneficial to the treatment of neurodegenerative diseases including ischemic stroke. In particular, its major component, cornel iridoid glycoside (CIG), was evidenced to exhibit neuroprotective effects against cerebral ischemic/reperfusion injury (CIR/I). Aimed to explore the effects of the CIG on brain edema of the CIR/I rats, the CIG was analyzed with the main constituents by using HPLC. The molecular docking analysis was performed between the CIG constituents and AQP4-M23. TGN-020, an AQP4 inhibitor, was used as a comparison. In the in vivo experiments, the rats were pre-treated with the CIG and were injured by performing middle cerebral artery occlusion/reperfusion (MCAO/R). After 24 h, the rats were examined for neurological function, pathological changes, brain edema, and polarized Aqp4 expressions in the brain. The HPLC analysis indicated that the CIG was composed of morroniside and loganin. The molecular docking analysis showed that both morroniside and loganin displayed lower binding energies to AQP4-M23 than TGN-020. The CIG pre-treated rats exhibited fewer neurological function deficits, minimized brain swelling, and reduced lesion volumes compared to the MCAO/R rats. In the peri-infarct and infarct regions, the CIG pre-treatment restored the polarized Aqp4 expression which was lost in the MCAO/R rats. The results suggested that the CIG could attenuate brain edema of the cerebral ischemia/reperfusion rats by modulating the polarized Aqp4 through the interaction of AQP4-M23 with morroniside and loganin.


Subject(s)
Aquaporin 4 , Brain Edema , Cornus , Iridoid Glycosides , Iridoids , Molecular Docking Simulation , Neuroprotective Agents , Reperfusion Injury , Animals , Male , Rats , Aquaporin 4/metabolism , Brain/drug effects , Brain Edema/drug therapy , Brain Ischemia/drug therapy , Cornus/chemistry , Glycosides , Infarction, Middle Cerebral Artery/drug therapy , Iridoid Glycosides/pharmacology , Iridoid Glycosides/isolation & purification , Iridoids/pharmacology , Molecular Structure , Neuroprotective Agents/pharmacology , Rats, Sprague-Dawley , Reperfusion Injury/drug therapy
12.
Neurobiol Dis ; 199: 106586, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38950712

ABSTRACT

OBJECTIVE: The glymphatic system serves as a perivascular pathway that aids in clearing liquid and solute waste from the brain, thereby enhancing neurological function. Disorders in glymphatic drainage contribute to the development of vasogenic edema following cerebral ischemia, although the molecular mechanisms involved remain poorly understood. This study aims to determine whether a deficiency in dystrophin 71 (DP71) leads to aquaporin-4 (AQP4) depolarization, contributing to glymphatic dysfunction in cerebral ischemia and resulting in brain edema. METHODS: A mice model of middle cerebral artery occlusion and reperfusion was used. A fluorescence tracer was injected into the cortex and evaluated glymphatic clearance. To investigate the role of DP71 in maintaining AQP4 polarization, an adeno-associated virus with the astrocyte promoter was used to overexpress Dp71. The expression and distribution of DP71 and AQP4 were analyzed using immunoblotting, immunofluorescence, and co-immunoprecipitation techniques. The behavior ability of mice was evaluated by open field test. Open-access transcriptome sequencing data were used to analyze the functional changes of astrocytes after cerebral ischemia. MG132 was used to inhibit the ubiquitin-proteasome system. The ubiquitination of DP71 was detected by immunoblotting and co-immunoprecipitation. RESULTS: During the vasogenic edema stage following cerebral ischemia, a decline in the efflux of interstitial fluid tracer was observed. DP71 and AQP4 were co-localized and interacted with each other in the perivascular astrocyte endfeet. After cerebral ischemia, there was a notable reduction in DP71 protein expression, accompanied by AQP4 depolarization and proliferation of reactive astrocytes. Increased DP71 expression restored glymphatic drainage and reduced brain edema. AQP4 depolarization, reactive astrocyte proliferation, and the behavior of mice were improved. After cerebral ischemia, DP71 was degraded by ubiquitination, and MG132 inhibited the decrease of DP71 protein level. CONCLUSION: AQP4 depolarization after cerebral ischemia leads to glymphatic clearance disorder and aggravates cerebral edema. DP71 plays a pivotal role in regulating AQP4 polarization and consequently influences glymphatic function. Changes in DP71 expression are associated with the ubiquitin-proteasome system. This study offers a novel perspective on the pathogenesis of brain edema following cerebral ischemia.


Subject(s)
Aquaporin 4 , Brain Edema , Brain Ischemia , Dystrophin , Glymphatic System , Animals , Aquaporin 4/metabolism , Aquaporin 4/genetics , Mice , Glymphatic System/metabolism , Brain Ischemia/metabolism , Brain Ischemia/pathology , Brain Edema/metabolism , Dystrophin/metabolism , Dystrophin/deficiency , Male , Astrocytes/metabolism , Mice, Inbred C57BL , Infarction, Middle Cerebral Artery/metabolism
13.
Clin Neurophysiol ; 164: 149-160, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38896932

ABSTRACT

OBJECTIVE: We aimed to determine whether quantitative electroencephalography (QEEG) measures have predictive value for cerebral edema (CED) and clinical outcomes in acute ischemic stroke (AIS) patients with anterior circulation large vessel occlusion who underwent mechanical thrombectomy (MT). METHODS: A total of 105 patients with AIS in the anterior circulation were enrolled in this prospective study. The occurrence and severity of CED were assessed through computed tomography conducted 24 h after MT. Clinical outcomes were evaluated based on early neurological deterioration (END) and 3-month functional status, as measured by the modified Rankin scale (mRS). Electroencephalography (EEG) recordings were performed 24 h after MT, and QEEG indices were calculated from the standard 16 electrodes and 2 frontal channels (F3-C3, F4-C4). The delta/alpha ratio (DAR), the (delta + theta) / (alpha + beta) ratio (DTABR), and relative delta power were averaged over all electrodes (global) and the F3-C3 and F4-C4 channels (frontal). The predictive effect and value of QEEG indices for CED and clinical outcomes were assessed using ordinal and logistic regression models, as well as receiver operating characteristic (ROC) curves. RESULTS: Significantly, both global and frontal DAR were found to be associated with the severity of CED, END, and poor functional outcomes at 90 days, while global and frontal DTABR and relative delta power were not associated with outcomes. In ROC analysis, the best predictive effect was observed in frontal DAR, with an area under the curve of approximately 0.80. It exhibited approximately 75% sensitivity and 71% specificity for radiological and clinical outcomes when a threshold of 3.3 was used. CONCLUSIONS: QEEG techniques may be considered an efficient bedside monitoring method for assessing treatment efficacy, identifying patients at higher risk of severe CED and END, and predicting long-term functional outcomes. SIGNIFICANCE: QEEG can help identify patients at risk of severe neurological complications that can impact long-term functional recovery in AIS patients who underwent MT.


Subject(s)
Brain Edema , Electroencephalography , Thrombectomy , Humans , Male , Female , Aged , Brain Edema/physiopathology , Brain Edema/diagnostic imaging , Brain Edema/etiology , Middle Aged , Thrombectomy/methods , Electroencephalography/methods , Prospective Studies , Delta Rhythm/physiology , Treatment Outcome , Alpha Rhythm/physiology , Ischemic Stroke/physiopathology , Ischemic Stroke/surgery , Aged, 80 and over , Stroke/physiopathology , Stroke/surgery , Predictive Value of Tests
14.
Eur Stroke J ; : 23969873241260965, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38872264

ABSTRACT

INTRODUCTION: Malignant middle cerebral artery infarction (MCI) needs rapid intervention. This study aimed to enhance the prediction of MCI using computed tomography perfusion (CTP) with varied quantitative benchmarks. MATERIALS AND METHODS: We retrospectively analyzed 253 patients from a single-center registry presenting with acute, severe, proximal large vessel occlusion studied with whole-brain CTP imaging at hospital arrival within the first 24 h of symptoms-onset. MCI was defined by clinical and imaging criteria, including decreased level of consciousness, anisocoria, death due to cerebral edema, or need for decompressive craniectomy, together with midline shift ⩾6 mm, or infarction of more than 50% of the MCA territory. The predictive accuracy of baseline ASPECTS and CTP quantifications for MCI was assessed by receiver operating characteristic (ROC) area under the curve (AUC) while F-score was calculated as an indicator of precision and sensitivity. RESULTS: Sixty-three out of 253 patients (25%) fulfilled MCI criteria and had worse clinical and imaging results than the non-MCI group. The capacity to predict MCI was lower for baseline ASPECTS (AUC 0.83, F-score 0.52, Youden's index 6), than with perfusion-based measures: relative cerebral blood volume threshold <40% (AUC 0.87, F-score 0.71, Youden's index 34 mL) or relative cerebral blood flow threshold <35% (AUC 0.87, F-score 0.62, Youden's index 67 mL). CTP based on rCBV measurements identified twice as many MCI as baseline CT ASPECTS. DISCUSSION AND CONCLUSION: CTP-based quantifications may offer enhanced predictive capabilities for MCI compared to non-contrast baseline CT ASPECTS, potentially improving the monitoring of severe ischemic stroke patients at risk of life-threatening edema and its treatment.

15.
Int J Mol Sci ; 25(12)2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38928322

ABSTRACT

Despite continuous medical advancements, traumatic brain injury (TBI) remains a leading cause of death and disability worldwide. Consequently, there is a pursuit for biomarkers that allow non-invasive monitoring of patients after cranial trauma, potentially improving clinical management and reducing complications and mortality. Aquaporins (AQPs), which are crucial for transmembrane water transport, may be significant in this context. This study included 48 patients, with 27 having acute (aSDH) and 21 having chronic subdural hematoma (cSDH). Blood plasma samples were collected from the participants at three intervals: the first sample before surgery, the second at 15 h, and the third at 30 h post-surgery. Plasma concentrations of AQP1, AQP2, AQP4, and AQP9 were determined using the sandwich ELISA technique. CT scans were performed on all patients pre- and post-surgery. Correlations between variables were examined using Spearman's nonparametric rank correlation coefficient. A strong correlation was found between aquaporin 2 levels and the volume of chronic subdural hematoma and midline shift. However, no significant link was found between aquaporin levels (AQP1, AQP2, AQP4, and AQP9) before and after surgery for acute subdural hematoma, nor for AQP1, AQP4, and AQP9 after surgery for chronic subdural hematoma. In the chronic SDH group, AQP2 plasma concentration negatively correlated with the midline shift measured before surgery (Spearman's ρ -0.54; p = 0.017) and positively with hematoma volume change between baseline and 30 h post-surgery (Spearman's ρ 0.627; p = 0.007). No statistically significant correlation was found between aquaporin plasma levels and hematoma volume for AQP1, AQP2, AQP4, and AQP9 in patients with acute SDH. There is a correlation between chronic subdural hematoma volume, measured radiologically, and serum AQP2 concentration, highlighting aquaporins' potential as clinical biomarkers.


Subject(s)
Aquaporin 2 , Biomarkers , Brain Edema , Humans , Male , Female , Biomarkers/blood , Middle Aged , Aged , Prognosis , Brain Edema/blood , Brain Edema/etiology , Brain Edema/diagnostic imaging , Aquaporin 2/blood , Aquaporin 2/metabolism , Adult , Craniocerebral Trauma/blood , Craniocerebral Trauma/complications , Hematoma, Subdural, Chronic/blood , Hematoma, Subdural, Chronic/surgery , Aquaporin 1/blood , Aquaporin 1/metabolism , Tomography, X-Ray Computed , Brain Injuries, Traumatic/blood , Brain Injuries, Traumatic/diagnosis , Aquaporins/blood , Aquaporins/metabolism
16.
Int J Mol Sci ; 25(12)2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38928258

ABSTRACT

Aquaporins (AQPs), particularly AQP4, play a crucial role in regulating fluid dynamics in the brain, impacting the development and resolution of edema following traumatic brain injury (TBI). This review examines the alterations in AQP expression and localization post-injury, exploring their effects on brain edema and overall injury outcomes. We discuss the underlying molecular mechanisms regulating AQP expression, highlighting potential therapeutic strategies to modulate AQP function. These insights provide a comprehensive understanding of AQPs in TBI and suggest novel approaches for improving clinical outcomes through targeted interventions.


Subject(s)
Aquaporins , Brain Injuries, Traumatic , Brain Injuries, Traumatic/metabolism , Humans , Animals , Aquaporins/metabolism , Brain Edema/metabolism , Brain Edema/etiology , Aquaporin 4/metabolism , Hydrodynamics , Brain/metabolism
17.
Heliyon ; 10(10): e31184, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38799755

ABSTRACT

The effectiveness of radiation therapy in the treatment of cerebral cavernous malformations (CCM) remains debatable. However, numerous studies have shown a reduction in hemorrhage risk following radiotherapy for CCM. Therefore, herein, we share our experiences utilizing linear accelerator (LINAC)-based radiation for treating CCMs, with the aim of identifying the key factors influencing the therapeutic outcomes. We conducted a retrospective review of all patients with non-brainstem CCMs who underwent radiation treatment, as recorded in the NOVALIS registry at our institution. T2-weighted MR images were used for volumetric assessments using the iPlan radiotherapy planning software. To determine the independent predictors of nidus volume reduction and perilesional brain edema (PBE), we performed multivariate Cox regression analysis to calculate hazard ratios. Twenty patients with 31 non-brainstem CCMs were enrolled in this study. Analysis revealed age as an independent predictive factor for both nidus volume reduction and PBE after radiation treatment for CCM. Furthermore, a single fraction dose of 17 Gy or more was identified as an independent predictor of nidus volume decrease, while a single fraction dose of 18 Gy or more was found to be an independent risk factor for PBE in patients with CCM following LINAC-based radiation therapy. LINAC-based radiation therapy for non-brainstem CCMs with a single fraction radiation dose between 16.5 and 17.5 Gy, or a biologically equivalent dose of approximately 120 Gy, may be the most effective at reducing nidus volume and limiting side effects, particularly in patients under the age of 55 years. We further observed that the risk of PBE increased as the maximum radiation dose delivered to a 1 cc volume of the surrounding normal brain exceeded approximately 17.3 Gy. Therefore, we believe that calculating the D1cc of the normal brain may help to predict the occurrence of PBE when radiotherapy is administered to non-brainstem CCMs.

18.
Neurol Int ; 16(3): 590-604, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38804483

ABSTRACT

OBJECTIVE: There is a relationship between the incidence of spontaneous intracerebral haemorrhage (ICH) and age. The incidence increases with age. This study aims to facilitate the decision-making process in the treatment of ICH. It therefore investigated the outcome after ICH and decompressive craniectomy (DC) in older adults (>65 years of age). METHODS: Retrospective, multicentre, descriptive observational study including only consecutive patients who received DC as the consequence of ICH. Additive evacuation of ICH was performed after the individual decision of the neurosurgeon. Besides demographic data, clinical outcomes both at discharge and 12 months after surgery were evaluated according to the Glasgow Outcome Scale (GOS). Patients were divided into age groups of ≤65 and >65 years and cohorts with favourable outcome (GOS IV-V) and unfavourable outcome (GOS I to III). RESULTS: 56 patients were treated. Mean age was 53.3 (SD: 16.13) years. There were 41 (73.2%) patients aged ≤65 years and 15 (26.8%) patients aged >65 years. During hospital stay, 10 (24.4%) patients in the group of younger (≤65 years) and 5 (33.3%) in the group of older patients (>65 years) died. Mean time between ictus and surgery was 44.4 (SD: 70.79) hours for younger and 27.9 (SD: 41.71) hours for older patients. A disturbance of the pupillary function on admission occurred in 21 (51.2%) younger and 2 (13.3%) older patients (p = 0.014). Mean arterial pressure was 99.9 (SD: 17.00) mmHg for younger and 112.9 (21.80) mmHg in older patients. After 12 months, there was no significant difference in outcome between younger patients (≤65 years) and older patients (>65 years) after ICH and DC (p = 0.243). Nevertheless, in the group of younger patients (≤65 years), 9% had a very good and 15% had a good outcome. There was no good recovery in the group of older patients (>65 years). CONCLUSION: Patients >65 years of age treated with microsurgical haematoma evacuation and DC after ICH are likely to have a poor outcome. Furthermore, in the long term, only a few older adults have a good functional outcome with independence in daily life activities.

19.
Heliyon ; 10(10): e30700, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38770322

ABSTRACT

Rare sugars, which exist only in very small quantities in nature, have recently attracted attention for their various biological functions in medicine. Among them, d-allose is known to have cytoprotective effects by antioxidant effects. In this study, we investigated whether the antioxidant effects of d-allose reduce brain edema in a water intoxication model of cytotoxic brain edema. Methods: Mice were injected intraperitoneally with distilled water (10 % of body weight) to create a model of brain edema. d-allose was administered orally at 400 mg/kg 30 min before the model was created. Two hours later, the degree of brain edema was measured by the dry-weight method to determine whether d-allose reduced brain edema. As an index of antioxidant effects, we measured changes over time in inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6) induced by the water intoxication model, and whether d-allose reduced inflammatory cytokines 4 h after model creation. Results: Administration of d-allose significantly suppressed brain edema formation of the water-intoxication model. And it significantly reduced inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6). These results suggest that the antioxidant effect of d-allose exerts an anti-inflammatory effect and reduces brain edema.

20.
Glia ; 72(9): 1629-1645, 2024 09.
Article in English | MEDLINE | ID: mdl-38785370

ABSTRACT

We have previously shown that phosphodiesterase 4 (PDE4) inhibition protects against neuronal injury in rats following middle cerebral artery occlusion/reperfusion (MCAO/R). However, the effects of PDE4 on brain edema and astrocyte swelling are unknown. In this study, we showed that inhibition of PDE4 by Roflumilast (Roflu) reduced brain edema and brain water content in rats subjected to MCAO/R. Roflu decreased the expression of aquaporin 4 (AQP4), while the levels of phosphorylated protein kinase B (Akt) and forkhead box O3a (FoxO3a) were increased. In addition, Roflu reduced cell volume and the expression of AQP4 in primary astrocytes undergoing oxygen and glucose deprivation/reoxygenation (OGD/R). Consistently, PDE4B knockdown showed similar effects as PDE4 inhibition; and PDE4B overexpression rescued the inhibitory role of PDE4B knockdown on AQP4 expression. We then found that the effects of Roflu on the expression of AQP4 and cell volume were blocked by the Akt inhibitor MK2206. Since neuroinflammation and astrocyte activation are the common events that are observed in stroke, we treated primary astrocytes with interleukin-1ß (IL-1ß). Astrocytes treated with IL-1ß showed decreased AQP4 and phosphorylated Akt and FoxO3a. Roflu significantly reduced AQP4 expression, which was accompanied by increased phosphorylation of Akt and FoxO3a. Furthermore, overexpression of FoxO3a partly reversed the effect of Roflu on AQP4 expression. Our findings suggest that PDE4 inhibition limits ischemia-induced brain edema and astrocyte swelling via the Akt/FoxO3a/AQP4 pathway. PDE4 is a promising target for the intervention of brain edema after cerebral ischemia.


Subject(s)
Aminopyridines , Aquaporin 4 , Astrocytes , Benzamides , Brain Edema , Infarction, Middle Cerebral Artery , Phosphodiesterase 4 Inhibitors , Rats, Sprague-Dawley , Reperfusion Injury , Animals , Aquaporin 4/metabolism , Aquaporin 4/genetics , Astrocytes/metabolism , Astrocytes/drug effects , Reperfusion Injury/metabolism , Phosphodiesterase 4 Inhibitors/pharmacology , Male , Brain Edema/metabolism , Brain Edema/etiology , Brain Edema/pathology , Aminopyridines/pharmacology , Benzamides/pharmacology , Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism , Cyclopropanes/pharmacology , Forkhead Box Protein O3/metabolism , Rats , Proto-Oncogene Proteins c-akt/metabolism , Cells, Cultured , Brain Ischemia/metabolism , Brain Ischemia/pathology , Disease Models, Animal , Interleukin-1beta/metabolism
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