Brain Edema Research Articles

Alternating cerebral edema and arterial dilations in Molybdenum cofactor deficiency type-A.

Alternating cerebral edema and arterial dilations in Molybdenum cofactor deficiency type-A.

Intravenous Administration of Anti-CD47 Antibody Augments Hematoma Clearance, Mitigates Acute Neuropathology, and Improves Cognitive Function in a Rat Model of Penetrating Traumatic Brain Injury.

Traumatic brain injury (TBI)-induced intracerebral hematoma is a major driver of secondary injury pathology such as neuroinflammation, cerebral edema, neurotoxicity, and blood-brain barrier dysfunction, which contribute to neuronal loss, motor deficits, and cognitive impairment. Cluster of differentiation 47 (CD47) is an antiphagocytic cell surface protein inhibiting hematoma clearance. This study was designed to evaluate the safety and efficacy of blockade of CD47 via intravenous (i.v.) administration of anti-CD47 antibodies following penetrating ballistic-like brain injury (PBBI) with significant traumatic intracerebral hemorrhage (tICH). The pharmacokinetic (PK) profile of the anti-CD47 antibody elicited that antibody concentration decayed over 7 days post-administration. Blood tests and necropsy analysis indicated no severe adverse events following treatment. Cerebral hemoglobin levels were significantly increased after injury, however, anti-CD47 antibody administration at 0.1 mg/kg resulted in a significant reduction in cerebral hemoglobin levels at 72 h post-administration, indicating augmentation of hematoma clearance. Immunohistochemistry assessment of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule 1 (IBA1) demonstrated a significant reduction of GFAP levels in the lesion core and peri-lesional area. Based on these analyses, the optimal dose was identified as 0.1 mg/kg. Lesion volume showed a reduction following treatment. Rotarod testing revealed significant motor deficits in all injured groups but no significant therapeutic benefits. Spatial learning performance revealed significant deficits in all injured groups, which were significantly improved by the last testing day. Anti-CD47 antibody treated rats showed significantly improved attention deficits, but not retention scores. These results provide preliminary evidence that blockade of CD47 using i.v. administration of anti-CD47 antibodies may serve as a potential therapeutic for TBI with ICH.

1011 A Rare Case of Left Sided Hemiparesis Following a Pneumatic Gun-Shot Injury to Left Anterior Chest Wall in a 13-Year-Old Boy

Abstract Introduction Even though pneumatic weapons rarely cause severe direct trauma, pellet embolisation can lead to unexpected, catastrophic events. Case Report A 13-year-old, previously healthy boy was injured by an accidentally fired pneumatic gun, while playing with his twin brother. He sustained a penetrating wound to left anterior chest wall and resultant bleeding was self-limiting. He was hospitalised within 15minutes. On admission, he was hemodynamically stable with normal Respiratory, Cardiovascular and Neurological system findings. Entry wound measuring 5*5 mm was present at 5th intercostal space just left to the sternum. No exit wound was detected. Initial chest radiograph and ultra-sound abdomen and chest were normal. 2D echocardiogram revealed only a very thin layer(3mm) of pericardial effusion. Four hours later, He developed a focal seizure followed by left sided hemiparesis. Urgent NCCT brain and carotid artery duplex showed a high dense pellet in right internal carotid artery at the level of petrous temporal bone and hypo-dense Middle Cerebral Artery (MCA) suggestive of right MCA thrombosis. He was transferred to a tertiary care centre. Interventional radiological and endo-vascular attempts of pellet retrieval have been failed. Ischemic stroke pursued with worsening cerebral oedema; thus decompression craniotomy was performed on day 3. He is currently being rehabilitated in a specialised centre. Conclusions High degree of suspicion should be maintained on the possibility of projectile embolisation, in pneumatic gun-shot injuries, especially in the absence of an exit wound. Extensive early investigations should be performed to localise the projectile and retrieval should be planned.

The effects and mechanisms of AM1241 in alleviating cerebral ischemia-reperfusion injury

ObjectiveResearch has shown that cerebral ischemia-reperfusion injury (CIRI) involves a series of physiological and pathological mechanisms, including inflammation, oxidative stress, and cell apoptosis. The cannabinoid receptor 2 agonist AM1241 has been found to have anti-inflammatory and anti-oxidative stress effects. However, it is unclear whether AM1241 has a protective effect against brain ischemia-reperfusion injury, and its underlying mechanisms are not yet known. MethodsIn this study, we investigated the anti-inflammatory, anti-oxidative stress, and anti-apoptotic effects of AM1241 and its mechanisms in BV2 cells stimulated with H2O2 and in a C57BL/6 mouse model of CIRI in vitro and in vivo, respectively. ResultsIn vitro, AM1241 significantly inhibited the release of pro-inflammatory cytokines TNF-α and IL-6, reactive oxygen species (ROS), and the increase in Toll-like receptor 4/myeloid differentiation protein 2 (MD2/TLR4) complex induced by H2O2. Under H2O2 stimulation, MD2 overexpression resulted in increased levels of MD2/TLR4 complex, TNF-α, IL-6, NOX2, BAX, and Cleaved-Caspase3 (C-Caspase3), as well as the activation of the MAPK pathway and NF-κB, which were reversed by AM1241. In addition, molecular docking experiments showed that AM1241 directly interacted with MD2. Surface Plasmon Resonance (SPR) experiments further confirmed the binding of AM1241 to MD2. In vivo, AM1241 significantly attenuated neurofunctional impairment, brain edema, increased infarct volume, oxidative stress levels, and neuronal apoptosis in CIRI mice overexpressing MD2. ConclusionOur study demonstrates for the first time that AM1241 alleviates mouse CIRI by inhibiting the MD2/TLR4 complex, exerting anti-inflammatory, anti-oxidative stress and anti-apoptotic effects.

Reducing Brain Edema Using Berotralstat, an Inhibitor of Bradykinin, Repurposed as Treatment Adjunct in Glioblastoma

Glioblastomas synthesize, bear receptors for, and respond to bradykinin, triggering migration and proliferation. Since centrifugal migration into uninvolved surrounding brain tissue occurs early in the course of glioblastoma, this attribute defeats local treatment attempts and is the primary reason current treatments almost always fail. Stopping bradykinin-triggered migration would be a step closer to control of this disease. The recent approval and marketing of an oral plasma kallikrein inhibitor, berotralstat (Orladeyo™), and pending FDA approval of a similar drug, sebetralstat, now offers a potential method for reducing local bradykinin production at sites of bradykinin-mediated glioblastoma migration. Both drugs are approved for treating hereditary angioedema. They are ideal for repurposing as a treatment adjunct in glioblastoma. Furthermore, it has been established that peritumoral edema, a common problem during the clinical course of glioblastoma, is generated in large part by locally produced bradykinin via kallikrein action. Both brain edema and the consequent use of corticosteroids both shorten survival in glioblastoma. Therefore, by (i) migration inhibition, (ii) growth inhibition, (iii) edema reduction, and (iv) the potential for less use of corticosteroids, berotralstat may be of service in treatment of glioblastoma, slowing disease progression. This paper recounts the details and past research on bradykinin in glioblastoma and the rationale of treating it with berotralstat.

Association of Dynamic Trajectories of Time-Series Data and Life-Threatening Mass Effect in Large Middle Cerebral Artery Stroke.

Life-threatening, space-occupying mass effect due to cerebral edema and/or hemorrhagic transformation is an early complication of patients with middle cerebral artery stroke. Little is known about longitudinal trajectories of laboratory and vital signs leading up to radiographic and clinical deterioration related to this mass effect. We curated a retrospective data set of 635 patients with large middle cerebral artery stroke totaling 95,463 data points for 10 longitudinal covariates and 40 time-independent covariates. We assessed trajectories of the 10 longitudinal variables during the 72h preceding three outcomes representative of life-threatening mass effect: midline shift ≥ 5mm, pineal gland shift (PGS) > 4mm, and decompressive hemicraniectomy (DHC). We used a "backward-looking" trajectory approach. Patients were aligned based on outcome occurrence time and the trajectory of each variable was assessed before that outcome by accounting for cases and noncases, adjusting for confounders. We evaluated longitudinal trajectories with Cox proportional time-dependent regression. Of 635 patients, 49.0% were female, and the mean age was 69years. Thirty five percent of patients had midline shift ≥ 5mm, 24.3% of patients had PGS > 4mm, and 10.7% of patients underwent DHC. Backward-looking trajectories showed mild increases in white blood cell count (10-11K/UL within 72h), temperature (up to half a degree within 24h), and sodium levels (1-3mEq/L within 24h) before the three outcomes of interest. We also observed a decrease in heart rate (75-65 beats per minute) 24h before DHC. We found a significant association between increased white blood cell count with PGS > 4mm (hazard ratio 1.05, p value 0.007). Longitudinal profiling adjusted for confounders demonstrated that white blood cell count, temperature, and sodium levels appear to increase before radiographic and clinical indicators of space-occupying mass effect. These findings will inform the development of multivariable dynamic risk models to aid prediction of life-threatening, space-occupying mass effect.

Serial Assessment of Hemodynamic and Cerebrovascular Changes After Administration of Mannitol in Postoperative Neurosurgical Patients in the Intensive Care Unit: A Combined Transthoracic and Transcranial Color Doppler Study.

Mannitol is widely used in neurosurgical units to mitigate raised intracranial pressure and cerebral edema, crucial in postoperative management. Its hyperosmolar properties reduce brain extracellular fluid, thereby altering cerebral perfusion and cardiac dynamics. However, the temporal and combined effects of mannitol on cardiovascular and cerebrovascular parameters remain inadequately explored in postoperative settings. This prospective observational study enrolled 20 adult patients who underwent elective craniotomies for tumor excision. Mannitol was administered to the patients at a dose of 0.5 mg/kg/dose as a bolus dose over 20 to 30 minutes. The time interval was eight hours between the doses (scheduled dosing). Patients received their first dose of mannitol in the ICU after eight hours of intraoperative dose. The patients were given mannitol for two postoperative days and followed up for two days in the postoperative period. Transthoracic echocardiography and transcranial color Doppler were used to assess cardiovascular and cerebrovascular parameters at multiple intervals post-mannitol administration. Significant increases in mean flow velocities were observed bilaterally immediately post-mannitol administration on the first postoperative day, indicative of improved cerebral blood flow. However, these changes were transient, with no significant variations noted on the second postoperative day. Cerebrovascular resistance, as measured by the pulsatility index, showed non-significant changes bilaterally across both days. Cardiovascular parameters, including stroke volume and cardiac output, remained stable throughout the study period. Mannitol administration at 0.5 g/kg in postoperative neurosurgical patients transiently improves cerebral perfusion without causing significant hemodynamic instability. This study underscores the importance of monitoring both cerebrovascular and cardiovascular parameters post-mannitol administration to optimize patient management and outcomes.

Contrast-induced transient cortical blindness

A 58-year-old Malay man with a history of ischemic heart disease, well-controlled diabetes mellitus, and hypertension presented with sudden loss of vision after he underwent angiogram (cardiac catheterization) with contrast. Post-angiogram, his visual acuity deteriorated gradually to no perception of light bilaterally within 1 h duration. Clinically, there was no new intraocular pathology and neurologic examination was normal. An urgent noncontract computed tomography (CT) scan of the brain showed the presence of contrast in the venous sinuses but no obvious acute intracranial hemorrhage. Bilateral frontal and anterior parietal regions appeared hypodense with loss of gray white matter differentiation and relative effacement of the sulci. CT brain reported that infarction or cerebral edema may represent. Patient’s condition was observed, and after 24 h, his vision recovered to baseline and he was discharged well.

Comparative Evaluation of Neuroprotective Activity of Tryptanthrin and Its Oxime in Middle Cerebral Artery Occlusion in Rats.

The neuroprotective activity of tryptanthrin and its oxime was compared in male Wistar rats with a model of intraluminal occlusion of the middle cerebral artery. Neurobehavioral tests were performed 4, 24, and 48 h after focal cerebral infarction (FCI) using a modified neurological severity score (mNSS); additionally, the horizontal stability test, the plantar sensitivity test of the fore and hind limbs, holding on the tilted cage top test, and negative geotaxis test were performed. The size of FCI and the severity of brain tissue swelling were examined on day 2 after occlusion. Tryptanthrin and its oxime were administered at a dose of 10 mg/kg intraperitoneally during FCI, then daily for 2 days. In the control group, the mean score of neurological deficit remained at a high level for 2 days. FCI size was 43.8±3.4% of hemisphere area, and the hemisphere volume increased by 18.5±2.0% due to brain tissue swelling and edema. Administration of tryptanthrin and its oxime significantly decreased neurological deficits at all control points and reduced FCI size (by 24.2 and 30.4%, respectively) and brain tissue swelling of the affected hemisphere (by 64.9 and 62.7%, respectively). Therefore, the neuroprotective effect of tryptanthrine and its oxime in the acute period of FCI is largely determined by their anti-inflammatory activity.

VASCULAR PARKINSONISM WITH EARLY COGNITIVE IMPAIRMENT: A CASE REPORT AND LITERATURE REVIEW

Cerebral venous sinus thrombosis (CVST) is an uncommon condition of cerebral venous sinus thrombosis with a varied clinical presentation that can be diagnostically challenging. Intravenous heparin is the optimal immediate anticoagulant according to the European Academy of Neurology (EAN) guideline 2017. This report aims to describe highly suspicious CVST clinical features and suggest a diagnostic algorithm based on two cases of CVST found in our center. The first case is a 52-year-old man who presented with serial seizures preceded by subacute headache and diparesis. Non-contrast head CT (NCCT) showed multifocal haemorrhages and cord signs. The second case is a 19-year-old woman who presented with slowly decreased consciousness, headache, and a history of upper respiratory infection. Diffuse cerebral edema was revealed in NCCT. Both of these patients had thrombosis in superior sagittal sinus, right transverse, and sigmoid sinus. Heparinization was conducted and continued with rivaroxaban with a good response. CVST is rare case and often unrecognized; since it has serious complications, early diagnosis and treatment improve prognosis and survival.

An integrated nomogram combining clinical and radiomic features of hyperattenuated imaging markers to predict malignant cerebral edema following endovascular thrombectomy.

Malignant cerebral edema (MCE), a potential complication following endovascular thrombectomy (EVT) in the treatment of acute ischemic stroke (AIS), can result in significant disability and mortality. This study aimed to develop a nomogram model based on the hyperattenuated imaging marker (HIM), characterized by hyperattenuation on head noncontrast computed tomography (CT) immediately after thrombectomy, to predict MCE in patients receiving EVT. In this retrospective cohort study, we selected 151 patients with anterior circulation large-vessel occlusion who received endovascular treatment. The patients were randomly allocated into training (n=121) and test (n=30) cohorts. HIM was used to extract radiomics characteristics. Conventional clinical and radiological features associated with MCE were also extracted. A model based on extreme gradient boosting (XGBoost) machine learning using fivefold cross-validation was employed to acquire radiomics and clinical features. Based on HIM, clinical and radiological signatures were used to construct a prediction nomogram for MCE. Subsequently, the signatures were merged through logistic regression (LR) analysis in order to create a comprehensive clinical radiomics nomogram. A total of 28 patients out of 151 (18.54%) developed MCE. The analysis of the receiver operating characteristic curve indicated an area under the curve (AUC) of 0.999 for the prediction of MCE in the training group and an AUC of 0.938 in the test group. The clinical and radiomics nomogram together showed the highest accuracy in predicting outcomes in both the training and test groups. The novel nomogram, which combines clinical manifestations and imaging findings based on postinterventional HIM, may serve as a predictor for MCE in patients experiencing AIS after EVT.

Step-down infusion of barbiturate improves neurofunction in a new rat model of rebleeding subarachnoid hemorrhage

Rebleeding from a ruptured aneurysm is a risk factor for fatal prognosis in subarachnoid hemorrhage (SAH). A novel barbiturate treatment, step-down infusion of barbiturate (sd-B), was previously developed; it showed beneficial effects on patients with severe traumatic brain injuries. The present study established a rebleeding SAH model in rats and evaluated the effect of sd-B. Fifty male Sprague-Dawley rats were divided into sham-operation with distilled water, sham-operation with barbiturate, SAH-rebleeding with distilled water, and SAH-rebleeding with barbiturate groups. For posttreatment with sd-B, thiamylal was intraperitoneally administered at 3 mg/kg/h on days 0–1, 2 mg/kg/h on days 1–2, and 1 mg/kg/h on days 2–3 after SAH using osmotic minipumps. We monitored neurofunction and case fatality as the primary endpoints and evaluated brain injuries, including brain edema and cortical neuronal cell death, as the secondary endpoints. Posttreatment with sd-B improved the modified Garcia test, reduced the brain water content, and inhibited the loss of neuronal cells and microglial expressions in the rat model. Our results revealed that sd-B ameliorated neurofunction and brain injuries on the rebleeding SAH model, suggesting that the novel treatment is a good candidate drug for patients with SAH with rebleeding.

The neuroprotective effects of normobaric oxygen therapy after stroke.

Stroke, including ischemic and hemorrhagic stroke, is a severe and prevalent acute cerebrovascular disease. The development of hypoxia following stroke can trigger a cascade of pathological events, including mitochondrial dysfunction, energy deficiency, oxidative stress, neuroinflammation, and excitotoxicity, all of which are often associated with unfavorable prognosis. Nonetheless, a noninvasive intervention, referred to as normobaric hyperoxia (NBO), is known to have neuroprotective effects against stroke. NBO can exert neuroprotective effects through various mechanisms, such as the rescue of hypoxic tissues, preservation of the blood-brain barrier, reduction of brain edema, alleviation of neuroinflammation, improvement of mitochondrial function, mitigation of oxidative stress, reduction of excitotoxicity, and inhibition of apoptosis. These mechanisms may help improve the prognosis of stroke patients. This review summarizes the mechanism by which hypoxia causes brain injury and how NBO can act as a neuroprotective therapy to treat stroke. We conclude that NBO has significant potential for treating stroke and may represent a novel therapeutic strategy.

Convexity Meningioma, Parasagittal Meningioma, Falx Meningioma

During surgery for meningioma, basic surgical techniques and strategies required for the removal of the tumor are common, particularly for tumors located superficially, such as convexity, parasagittal, and falx meningiomas. Four basic surgical techniques, including detachment; devascularization; debulking; and dissection should be combined and repeated in appropriate sequence, tailored to the specific conditions of each tumor. This eventually enables the total circumferential dissection of the tumor from the surrounding tissues. It is essential to retract the tumor towards the space created at the tumor center through internal debulking, rather than retracting the normal brain, to avoid damage to the surrounding brain tissue. During surgery for parasagittal meningioma with venous sinus occlusion, it is crucial to preserve the cortical veins that have developed as collateral pathways to prevent venous complications. During surgery for falx meningioma, the selection of a surgical approach including a contralateral approach based on factors such as the development of bridging veins and significant peritumoral brain edema is required. In this article, detailed surgical procedures for convexity meningioma, parasagittal meningioma, and falx meningioma were described focusing on the application of fundamental surgical techniques tailored to each tumor type.

Perioperative optic nerve sheath diameter variations in patients with end-stage renal failure undergoing robotic-assisted kidney transplant: a prospective observational study.

Patients with chronic kidney disease (CKD) who undergo hemodialysis are predisposed to interstitial cerebral edema. Robotic-assisted laparoscopic surgery can increase optic nerve sheath diameter (ONSD) and intracranial pressure. The impact of robotic-assisted kidney transplant (RAKT) on ONSD is complicated by the presence of CKD, the administration of furosemide and mannitol, and the manipulation of hemodynamics. We examined ONSD variations in patients undergoing RAKT over a 1-year period at our institution. Furthermore, we attempted to identify any perioperative hemodynamic factors influencing these changes. This prospective study included 20 patients undergoing RAKT. ONSD, heart rate, central venous pressure, systolic blood pressure, diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured following intubation (T1), after assuming the steep Trendelenburg position (T2), 1 hour after docking (T3), upon reperfusion (T4), after transition to the supine position (T5), and 3 hours postextubation (T6). Repeated measures analysis of variance with post hoc Bonferroni correction was employed to compare variables at each time point. Pearson correlation analysis was utilized to assess relationships between variables. P-values ≤0.05 were considered to indicate statistical significance. ONSD (in mm) increased from T1 (3.60±0.44) to T3 (4.06±0.45, P=0.002) and T4 (3.99±0.62, P=0.046), before falling to its lowest value at T6 (3.42±0.64, P=0.002). Pearson correlation analysis revealed significant correlations (P<0.05) between changes in ONSD at T3 and both DBP (r=0.637) and MAP (r=0.522). During RAKT with open ureteric anastomosis, ONSD initially increased, then decreased following reperfusion. DBP and MAP displayed positive correlations with ONSD changes at T3.

Investigating the therapeutic effects of nimodipine on vasogenic cerebral edema and blood-brain barrier impairment in an ischemic stroke rat model

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.

Dystrophin 71 deficiency causes impaired aquaporin-4 polarization contributing to glymphatic dysfunction and brain edema in cerebral ischemia

ObjectiveThe 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. MethodsA 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. ResultsDuring 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. ConclusionAQP4 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.

The cornel Iridoid glycoside attenuated brain edema of the cerebral ischemia/reperfusion rats by modulating the polarized aquaporin 4

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.

Hypertrophic Pachymeningitis, Associated with Eosinophilic Granulomatosis with Polyangiitis, and ANCA-Negative Serology.

Hypertrophic pachymeningitis (HP) is a disease with diverse aetiologies, including the autoimmune one, either associated with antineutrophil cytoplasmic antibodies or immunoglobulin G4. A 65-year-old woman with a history of systemic arterial hypertension, presented with intense progressive headaches. HP and hemispheric vasogenic oedema were observed by nuclear magnetic resonance (NMR) study. During the six months before the headache, she had developed progressive hearing loss which she attributed to age. A biopsy of dura mater showed necrotising vasculitis with peripheral inflammatory infiltrate, made up of accumulations of epithelioid cells and multinucleated giant cells, and abundant eosinophils. A final diagnosis of HP with eosinophilic granulomatosis with polyangiitis (EGPA) was made. The patient had eosinophilic granulomatosis with polyangiitis (EGPA) histology, ANCA-negative serology and HP. This case is important because it shows that EGPA seems to have a spectrum of clinical diseases, including HP with negative serology, and bilateral sensorineural hearing loss. We are facing a wide spectrum of EGPA, breaking the paradigm of only systemic involvement. Hypertrophic pachymeningitis (HP) has several aetiologies; if the systemic investigation is not contributory to a diagnosis, a meningeal biopsy is necessary.This is the first case report of HP, associated with eosinophilic granulomatosis with polyangiitis (EGPA), and ANCA-negative serology.EGPA is probably a spectrum of diseases with predominant systemic involvement, but there may be cases where there is histological evidence, without the systemic context or positive serology.

Pathomorphology of severe Grade 3-4 hepatic encephalopathy in decompensated cirrhosis patients with acute-on-chronic liver failure

The study was aimed to determine of the most significant pathomorphological signs of severe hepatic encephalopathy (HE) in deceased cirrhotic patients with acute-on-chronic liver failure (ACLF) syndrome based on changes of the glioneuronal complex and the level of tissue ammonia. Using pathohistological, histochemical, and immunohistochemical methods, the cerebral cortex, thalamus, striatum, and cerebellum of 21 deceased patients with acutely decompensated liver cirrhosis with ACLF syndrome and HE Grade 3-4 were examined in comparison with control group, which included 30 deceased patients from acute cardiovascular failure. The study revealed that during HE Grade 3-4 as a component of ACLF, in all studied brain regions, there was a reliably (p&lt;0.05) higher histochemical level of tissue ammonia (up to 500%), increased numbers (up to 215.69%) of apoptotic neurons (according to caspase-3), reduced (up to 119.60%) level of synaptophysin, increased expression of glutamine synthetase (up to 253.02%) and aquaporin-4 (up to 481.81%) associated by reduced (up to 296.81%) expression of glial fibrillary acidic protein in astrocytes, increased (up to 11-fold) numbers of Alzheimer type 2-astrocytes, expansion of perivascular and pericellular «edematous» spaces (up to 890.81%), increased numbers of amyloid bodies (up to 5-fold), increased area of immunopositive material of CD68+ microgliocytes (up to 114.78%) with an increase (up to 71.91%) in the proportion of CD68+ amoeboid microglia. The above-mentioned changes confirm that the loss of consciousness and other psychoneurological manifestations of severe HE Grade 3-4 are due to compound am­monia-associated changes in the components of the glioneuronal complex, namely: adaptive remodeling and dystro­phic changes in astrocytes, reduced synaptic transmission and apoptotic neuronal death, reactive changes in microglia with a small proportion of microgliocytes involved in phagocytosis, cytotoxic brain edema and dysfunction of the glymphatic system