Brain Edema Research Articles

HUC-MSCs Prevent Acute High-Altitude Injury through Apoe/Pdgf-b/p-Erk1/2 Axis in Mice.

The hypobaric hypoxic atmosphere can cause adverse reactions or sickness. The purpose of this study was to explore the preventive effect and mechanism of human umbilical cord mesenchymal stem cells (hUC-MSCs) on acute pathological injury in mice exposed to high-altitude. We pretreated C57BL/6 mice with hUC-MSCs via the tail vein injection, and then the mice were subjected to hypobaric hypoxic conditions for five days. The effects of hUC-MSCs on the pathological injury of lung, heart, brain were assessed by biochemical analysis, histopathological testing, quantitative real-time polymerase chain reaction (qPCR), and western blot (WB). Further, transcriptome sequencing was used to screen for the potential therapeutic targets of hUC-MSCs in acute pathological injury, the identified signaling axis was characterized using Apoe-/- mice, qPCR and WB. hUC-MSCs administration notably prevented and relieved gastrointestinal symptoms and inflammation of lung and heart, increased blood oxygen saturation and serum superoxide dismutase (SOD) level, decreased serum malondialdehyde (MDA) level, rescued lung tissue injury and myocardial mitochondrial disorder, elevated nissl bodies number in brain tissue and reduced the degree of pulmonary and cerebral edema. Furthermore, hUC-MSCs pretreatment reversed the down-regulated Apoe and up-regulated Pdgf-b and p-Erk1/2 in the lung of hypobaric hypoxic mice. Thus, hUC-MSCs protected against acute pathological injury caused by hypobaric hypoxic condition via the Apoe/Pdgf-b/p-Erk1/2 axis, and the identified pathway was confirmed by the negative results of Apoe-/- mice. hUC-MSCs possess the preventive effect on acute pathological injury caused by hypobaric hypoxia environment at high-altitude.

A fatal case of accidental asphyxia following nitrous oxide inhalation and alcohol consumption.

Nitrous oxide (N2O) abuse is becoming increasingly popular worldwide. Moreover, the use of N2O combined with other substances, such as alcohol, is also common. Accidental deaths associated with N2O abuse are rare in forensic practice, with most fatal cases involving continuous inhalation equipment or exposure in a confined space. In contrast, the inhalation of N2O using balloons is traditionally regarded as a relatively safe method. In this report, we present an unusual fatal case of a 16-year-old girl who died after drinking alcohol and inhaling N2O from balloons. The decedent was found in a prone position with the nose and mouth compressed against the bed. Cyanosis of nails, pulmonary and cerebral edema, and the positive expression of HIF-1α in lung, myocardium and brain, were indicative of asphyxiation. Toxicological analysis revealed a peripheral blood ethanol concentration of 140mg/dL and cardiac blood N2O concentration of 74.5 μL/mL. N2O was also positively detected in the lungs, stomach contents, gastric air, and the brain. In conclusion, we determined that the decedent died from accidental asphyxia related to N2O inhalation, prone positioning, and alcohol consumption. We also investigated chronic N2O abuse from a forensic perspective. This report aims to help forensic pathologists manage similar cases. It also reminds N2O abusers of potential dangers.

Hyponatremia is associated with malignant brain edema after mechanical thrombectomy in acute ischemic stroke

BackgroundHyponatremia (< 135 mmol/L) is the most common electrolyte disturbance in patients with stroke. However, few studies have reported the relationship between hyponatremia at admission and outcomes in patients with acute ischemic stroke (AIS) treated with mechanical thrombectomy (MT). This study is aimed to explore the association between hyponatremia and clinical outcomes following MT.MethodsA retrospective study was conducted at our center. The primary outcome was postoperative malignant brain edema (MBE). The secondary outcomes included mortality and adverse function at the 90-day follow-up, which were defined as modified Rankin scale scores of 6 and > 2, respectively. Patients were classified into hyponatremia and nonhyponatremia groups based on their serum sodium concentration at admission before drug use. The occurrence of MBE was evaluated via computed tomography after MT, and 90-day outcomes were obtained through in-person interviews at the clinic or via telephone. Multivariate analysis was performed to investigate the associations among postoperative MBE, 90-day mortality, adverse function and hyponatremia.ResultsA total of 342 patients were enrolled into the study, of whom 52 (15.2%) had hyponatremia, 86 (25.1%) developed postoperative MBE, 93 (27.2%) died within 90 days after MT, and 201 (58.8%) had adverse functions at the 90-day follow-up. Multivariate analysis revealed that hyponatremia was significantly associated with postoperative MBE (odds ratio [OR] 3.91, 95% confidence interval [CI] 1.66 − 9.23, p = 0.002), 90-day mortality (OR 5.49, 95% CI 2.48 − 12.14, p < 0.001), and 90-day adverse function (OR 3.25, 95% CI 1.29 − 8.12, p = 0.012). In addition, mediation analysis revealed that postoperative MBE may partially account for the 90-day mortality/adverse function of patients with hyponatremia (regression coefficients changed by 18.6% and 23.9%, respectively).ConclusionHyponatremia is an independent predictor of postoperative MBE, 90-day mortality, and adverse function. Correction of hyponatremia may reduce the postoperative MBE to improve the prognosis of patients.

Therapeutic effects of traditional Chinese medicine Hua-Feng-Dan in a rat model of ischemic stroke involve renormalization of gut microbiota

Hua-Feng-Dan is a traditional Chinese medicine used to treat ischemic stroke, but little is known about its therapeutic mechanism. This study explored whether and how the mechanism involves readjustment of gut microbiota. Rats were subjected to middle cerebral artery occlusion as a model of ischemic stroke or to sham surgery, then treated or not with Hua-Feng-Dan. The different groups of animals were compared in terms of neurological score, cerebral infarct volume, brain edema, brain and gut histopathology to assess stroke severity. They were also compared in terms of indices of intestinal barrier permeability, inflammation and oxidative stress, brain metabolites as well as composition of the gut microbiota and their metabolites. Hua-Feng-Dan significantly reduced cerebral infarct volume and brain water content and improved neurological score, ischemic brain histopathology, and gut histopathology. It partially reversed stroke-induced intestinal barrier disruption and leakage, inflammation, dyslipidemia and oxidative stress, as well as the stroke-induced increase in pathogenic gut microbiota (e.g., Escherichia-Shigella, Enterococcus, Clostridium_innocuum_group) and decrease in beneficial microbiota (e.g., Lachnospiraceae, unclassified__f__Lachnospiracea and Ruminococcus_torques_group). The treatment altered levels of 39 and 38 metabolites produced during gut microbial and brain tissue metabolism respectively, mainly of amino acids, nucleosides, short-chain fatty acids, and essential fatty acids. Levels of factors related to inflammation and intestinal barrier permeability correlated positively with relative abundance of Escherichia-Shigella and Clostridium_innocuum_group, and negatively with 4-(glutamylamino) butanoate, 2-hydroxy-3-methylbutyric acid, dihomo-α-linolenic acid, dihomolinoleic acid, and 10-nitrolinoleic acid. Conversely, levels of 4-(glutamylamino) butanoate, 2-hydroxy-3-methylbutyric acid, and 10-nitrolinoleic acid correlated positively with relative abundance of unclassified__f__Lachnospiracea. Our results suggest that Hua-Feng-Dan may mitigate ischemic stroke injury by renormalizing gut microbiota and restoring gut barrier function, gut metabolism, thereby helping to alleviate inflammatory, neurological damage, and brain metabolic disorders.

Ligustrazine hydrochloride Prevents Ferroptosis by Activating the NRF2 Signaling Pathway in a High-Altitude Cerebral Edema Rat Model

High-altitude cerebral edema (HACE) is a disorder caused by low pressure and hypoxia at high altitudes. Nevertheless, as of now, there is still a scarcity of safe and effective prevention and treatment methods. The active component of Ligusticum Chuanxiong, namely Ligustrazine hydrochloride (LH), has shown potential in the prevention and treatment of HACE due to its anti-inflammatory, antioxidant, and neuroprotective effects in nervous system disorders. Consequently, the potential protective effect of LH on HACE and its mechanism still need to be further explored. Prior to modeling, 90 male Sprague-Dawley rats were pretreated with different doses of drugs, including LH (100 mg/kg and 50 mg/kg), dexamethasone (4 mg/kg), and ML385 (30 mg/kg). Subsequently, the pretreated rats were placed in a low-pressure anoxic chamber simulating a plateau environment to establish the rat HACE model. The effects and mechanisms of LH on HACE rats were further elucidated through determination of brain water content, HE staining, ELISA, immunofluorescence, molecular docking, molecular dynamics simulation, western blot, and other techniques. The results showed, first of all, that LH pretreatment can effectively reduce brain water content; down-regulate the expression of AQP4, HIF-1α, and VEGF proteins; and alleviate damage to brain tissue and nerve cells. Secondly, compared with the HACE group, LH pretreatment can significantly reduce MDA levels and increase GSH and SOD levels. Additionally, LH decreased the levels of inflammatory factors IL-1β, IL-6, and TNF-α; reduced total iron content in brain tissue; increased the expression of ferroptosis-related proteins such as SLC7A11, GPX4, and FTH1; and alleviated ferroptosis occurrence. Molecular docking and molecular dynamics simulations show that LH has a strong binding affinity for NRF2 signaling. Western blot analysis further confirmed that LH promotes the translocation of NRF2 from the cytoplasm to the nucleus and activates the NRF2 signaling pathway to exert an antioxidant effect. The NRF2 inhibitor ML385 can reverse the anti-oxidative stress effect of LH and its protective effect on HACE rat brain tissue. In summary, LH may have a protective effect on HACE rats by activating the NRF2 signaling pathway, inhibiting ferroptosis, and resisting oxidative stress.

Expression of TNF-α, VEGF-A and Microvessel Density in Cerebral Alveolar Echinococcosis and Their Correlation with Perilesional Brain Edema.

Alveolar echinococcosis (AE) is an infrequent zoonosis caused by Echinococcus multilocularis with a high degree of disability and mortality. Metastatic cerebral alveolar echinococcosis (CAE) is very rare and the lesions could lead to severe perilesional brain edema (PLBE) and subsequent uncontrollable intracranial hypertension. In this study, we sought to determine the expression of edema-associated factors in CAE lesions and their associations with PLBE. We retrospectively evaluated the clinical data of 18 CAE patients who received craniotomy. Severity of PLBE was described by edema index (EI). Archived specimens were processed for immunohistochemistry to detect tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor A (VEGF-A) and microvessel density (MVD) in CAE lesions. Expression intensity of CAE lesions was quantified by integral optical density (IOD) or count and was compared to the control group. The results showed TNF-α and VEGF-A were significantly expressed in CAE lesions (p < 0.001), their levels were positively correlated with PLBE (TNF-α: r = 0.701, p = 0.001; VEGF-A: r = 0.803, p < 0.001). The MVD of CAE lesions had a similar expression with normal brain tissue, and it was positively correlated with PLBE and VEGF-A (PLBE: r = 0.849, p < 0.001; VEGF-A: r = 0.687, p = 0.002). In conclusion, we speculated the upregulation of TNF-α and VEGF-A induced the formation of PLBE. Besides, though there was no extra increase of MVD, it was still regulated by VEGF-A and provided a better anatomical basis for the formation of PLBE and further promoted it.

Evaluation of contralateral arterial flow compensation using transcranial Doppler in acute internal carotid artery occlusion and implications for neurological outcome

Acute internal carotid artery occlusion (AICAO) can result in malignant cerebral edema and unfavorable patient outcomes. This study evaluated the utility of transcranial Doppler (TCD) in assessing contralateral flow compensation and predicting outcomes in patients with AICAO. We enrolled 51 patients within 6 h of symptom onset and conducted TCD examinations to evaluate collateral circulation. Among the 51 patients, 40 (78.4%) had collateral flow. TCD showed excellent agreement with magnetic resonance angiography (MRA)/CT angiography (CTA) in assessing anterior communicating artery (ACoA) status (kappa = 0.873, p < 0.001). Our findings indicated that the absence of collaterals (OR = 7.649, p = 0.032), younger age (OR = 0.907, p = 0.048), and lower Alberta Stroke Program Early CT Score 24 h after onset (ASPECTs1) (OR = 0.276, p = 0.025) were independent predictors of malignant cerebral edema. Additionally, advanced age, elevated National Institutes of Health Stroke Scale Score (NIHSSs) in the Emergency Department, sole extracranial-to-intracranial collateral circulation (EICC), and absence ACoA were independently associated with worse outcomes (all p < 0.05). In conclusion, TCD evaluation of collateral circulation in AICAO patients can effectively predict the risk of malignant cerebral edema, with ACoA presence correlating with favorable outcomes and sole EICC linked to poorer prognosis. While age, NIHSSs and ASPECTs also contribute, TCD’s assessment of collaterals provides key insights for patient management.

Catechin-Based Polyphenol Nanoparticles Ameliorated Ferroptosis to Alleviate Brain Injury after Intracerebral Hemorrhage.

Spontaneous intracerebral hemorrhagic stroke (ICH) is a highly aggressive disease, with a high incidence and mortality rate. Iron deposition following ICH leads to oxidative damage and motor dysfunction, significantly impacting the overall quality of life for those affected. Here, a polyphenolic nanomedicine, catechin-based polyphenol nanoparticles surface-modified by thiol-terminated poly(ethylene glycol) (CNPs@PEG), was developed through the oxidative polymerization and self-assembly of catechin, a natural compound in tea. Due to its potent antioxidant and metal-chelating properties, CNPs@PEG effectively maintained blood-brain barrier integrity, reduced brain edema, significantly increased the survival rate of mice with cerebral hemorrhage and markedly improved neurological deficits after ICH. Mechanistically, CNPs@PEG accomplishes this by chelating iron, enhancing tissue antioxidant capacity, reducing oxidative stress, and inhibiting iron deposition. This approach holds promise as a targeted therapeutic strategy for addressing cerebral hemorrhage and other conditions associated with iron overload.

Mogroside V ameliorates astrocyte inflammation induced by cerebral ischemia through suppressing TLR4/TRADD pathway.

Inflammation and oxidative stress are pivotal factors in the onset and progression of secondary injury following cerebral ischemia-reperfusion (I/R). Mogroside V (MV), a primary active compound of Siraitia grosvenorii, exhibits significant anti-inflammatory and antioxidant properties. However, its specific effects in cerebral ischemia remain unclear. In this study, we evaluated the neuroprotective effects of MV in a model of focal cerebral ischemia. Male C57BL/6J mice were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) as an in vivo model of cerebral ischemia-reperfusion injury (CIRI), while U87 cells were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) to simulate CIRI in vitro. MV administration was found to reduce mortality, infarct volume, cerebral edema, and alleviate neurological deficits in these I/R mice. Furthermore, MV mitigated cerebral I/R injury by decreasing oxidative stress markers, such as reactive oxygen species (ROS) and malondialdehyde (MDA), while enhancing superoxide dismutase (SOD) levels. Gene Set Enrichment Analysis (GSEA) of the KEGG pathway revealed that most differentially expressed genes (DEGs) were involved in the Toll-like receptor/NF-κB/TNF/apoptosis signaling pathway. These findings were confirmed by real-time PCR, western blotting, immunohistochemistry, and immunofluorescence co-localization which demonstrated that MV reduced astrocyte inflammatory responses by inhibiting cytokine secretion associated with the TLR4/TRADD pathway. Additionally, MV protected neurons from apoptosis, as supported by TUNEL, Nissl, and HE staining. In conclusion, MV attenuates astrocyte inflammation and exerts neuroprotective effects following cerebral I/R injury, likely through suppression of the TLR4/TRADD signaling pathway.

Meningeal Metastasis from Naso-Ethmoidal Malignancies: Pathogenesis, Risk Factors, and Prognostic Impact

Introduction: Meningeal metastasis (MM) from naso-ethmoidal malignancies (NEMs) is rare, its metastatic route is still debated, and its prognostic impact remains unclear. Our aim is to analyze a retrospective series of NEMs with non-contiguous MM to study the possible route of spread and the prognostic value of MM. Materials and methods: The institutional database of SNC treated at the University of Brescia between 1995 and 2021 was reviewed. Clinical–pathological data were collected, and survivals were estimated with Kaplan–Meier. Univariate and multivariate logistic regression analysis were run to identify predictors of MM. Results: Among 296 patients, 17 experienced non-contiguous MM, all located along the dura. Intestinal-type adenocarcinoma (10/17) and olfactory neuroblastoma (3/17) were the most frequent histologies. At univariate analysis, brain edema (p &lt; 0.0001), resection (p = 0.026) or invasion (p = 0.006) of brain parenchyma, and local (p = 0.0004) and nodal (p = 0.021) recurrence were predictors of MM. At multivariate analysis, local recurrence was confirmed as an independent factor (odds ratio: 11.88, p = 0.0005). Dural surgical resection was not a risk factor. The five-year disease-specific survival was longer in patients with exclusive MM compared with patients with distant metastasis at other sites (64.3% vs. 30.1% p = 0.046). Conclusions: Dural venous shunt is the most likely pathway of spread of MM. Local recurrence is the only independent risk factor. Exclusive MM has a better prognosis than extrameningeal metastasis.

Chronic hypertension and perfusion deficits conjointly affect disease outcome after tPA treatment in a rodent model of thromboembolic stroke.

Futile recanalization hampers prognoses for ischemic stroke patients despite successful recanalization therapy. Allegedly, hypertension and reperfusion deficits contribute, but a better understanding is needed of how they interact and mediate disease outcome. We reassessed data from spontaneously hypertensive and normotensive Wistar-Kyoto rats (male, n = 6-7/group) that were subjected to two-hour embolic middle cerebral artery occlusion and thrombolysis in preclinical trials. Serial MRI allowed lesion monitoring and parcellation of regions-of-interest that represented infarcted (core) or recovered (perilesional) tissue. Imaging markers of hemodynamics and blood-brain barrier (BBB) status were related to tissue fate and neurological outcome. Despite comparable ischemic severity during occlusion between groups, hypertensive rats temporarily developed larger lesions after recanalization, with permanently aggravated vasogenic edema and BBB permeability. One day post-stroke, cerebral blood flow (CBF) was variably restored, but blood transit times were consistently prolonged in hypertensives. Compared to the core, perilesional CBF was normo-to-hyperperfused in both groups, yet this pattern reversed after seven days. Volumes of hypo- and hyperperfusion developed irrespective of strain, differentially associating with final infarct volume and behavioral outcome. Incomplete reperfusion and cerebral injury after thrombolysis were augmented in hypertensive rats. One day after thrombolysis, fractional volumes of hypoperfusion associated with worsened outcomes, while fractional volumes of hyperperfusion appeared beneficial or benign.

Analysis of clinical characteristics and risk factors for patients with heat stroke in western China in 2022: a multicenter retrospective study

ObjectivesTo analyzed the clinical characteristics and treatment modalities of heat stroke (HS) and to identify risk factors for a poor prognosis of HS and provide reference suggestions for its treatment and prevention.Measurements and main resultsWe enrolled a total of 247 patients, with hypertension, diabetes, and psychosis being the top three comorbidities associated with HS. The incidence of HS was higher among males and older individuals. Compared to the control group, the poor prognosis group experienced higher temperatures, a higher incidence of cerebral edema, and gastrointestinal bleeding (all p &amp;lt; 0.05). The poor prognosis group had significantly higher blood pH, HCO3-, Lac, Scr, AST, ALT, DBIL, CKMB, PT, DD, and PLT (all p &amp;lt; 0.05). Furthermore, logistic regression analysis revealed that Lac, Scr, and APACHE II were risk factors for poor prognosis (p &amp;lt; 0.05). The AUC values for the combined diagnostic model were 0.848 (95% CI: 0.781–0.914). Male morbidity, the number of patients with combined hypertension, the prognosis, and the APACHE II score and ALT level were all greater (p &amp;lt; 0.05) in the CHS group. The Kaplan–Meier analysis revealed that the CHS group had a significantly higher mortality rate than the EHS group.ConclusionA high incidence of hypertension, diabetes, psychosis, men, and older persons may be associated with HS. HS patients with high blood cell counts, impaired coagulation, liver and kidney diseases, and those with a specific type of CHS may face a poor prognosis. In patients with heart failure, APACHE II, Lac, and Scr were independent risk factors for a poor prognosis.

Methionine Sulfoximine as a Tool for Studying Temporal Lobe Epilepsy: Initiator, Developer, Attenuator.

Methionine sulfoximine (MSO) is a compound originally discovered as a byproduct of agene-based milled flour maturation. MSO irreversibly inhibits the astrocytic enzyme glutamine synthase (GS) but also interferes with the transport of glutamine (Gln) and of glutamate (Glu), and γ-aminobutyric acid (GABA) synthesized within the Glu/Gln-GABA cycle, in this way dysregulating neurotransmission balance in favor of excitation. No wonder that intraperitoneal administration of MSO has long been known to induce behavioral and/or electrographic seizures. Recently, a temporal lobe epilepsy (TLE) model based on local continuous infusion of MSO into the hippocampus has been developed reproducing the main features of human mesial TLE: induction of focal seizures, their spreading, increase in intensity over time, and development of spontaneous recurrent seizures. Fully developed TLE in this model is associated with hippocampal degeneration, hallmarked by reactive astrogliosis, and causally related to the concomitant loss of GS-containing astrocytes. By contrast, short-term pre-exposure of rats to relatively low MSO doses that only moderately inhibited GS, attenuated and delayed the initial seizures in the lithium-pilocarpine model of TLE and in other seizure-associated contexts: in the pentylenetetrazole kindling model in rat, and in spontaneously firing or electrically stimulated brain slices. The anti-initial seizure activity of MSO may partly bypass inhibition of GS: the postulated mechanisms include: (i) decreased release of excitatory neurotransmitter Glu, (ii) prevention or diminution of seizure-associated brain edema, (iii) stimulation of glycogenesis, an energy-sparing process; (iv) central or peripheral hypothermia. Further work is needed to verify either of the above mechanisms.

Nomogram model for decompressing craniectomy after mechanical thrombectomy in patients with acute ischemic stroke

The most common treatment method for patients with acute ischemic stroke with large vessel occlusion is mechanical thrombectomy. However, complications such as cerebral edema and hemorrhage transformation after MT can affect patient prognoses, while decompression craniectomy considerably improves patient prognoses. The aim of this study was to identify clinical indicators, such as the neutrophil/high-density lipoprotein cholesterol ratio, to predict DC. A retrospective analysis was conducted in AIS-LVO patients who received MT at Huizhou Central People’s Hospital and the Affiliated Hospital of Guilin Medical University. The patients were randomly divided into training, internal validation group and external validation group sets to generate and validate a nomogram model. Multivariate binary logistic analyses indicated that SBP > 178.5 mmHg, WBC > 12.05*109/L, PT > 14.54 s, and NHR > 8.874*109/mmol were independent risk factors for DC after MT in patients with AIS-LVO. In the training set, the area under the curve indicated good accuracy. Calibration curve results showed the average error in the training set was 0.038, and 0.036 in the validation set, showing good model fit. NHR was an independent risk factor for DC treatment after MT in AIS-LVO patients. A nomogram based on NHR accurately predicted if DC treatment was required after MT in patients with AIS-LVO.

Comparison of background characteristics and neuropathology findings between medico-legal autopsy cases with traumatic axonal injury, vascular axonal injury, or absence of axonal injury in β-amyloid precursor protein stain.

In forensic neuropathology, the β-amyloid precursor protein (β-APP) immunostain is used to diagnose axonal injury (AI). The two most common aetiologies are traumatic (TAI) and ischaemic (vascular; VAI). We aimed to identify background characteristics and neuropathology findings that are suggestive of TAI, VAI, or no AI in neuropathologically examined medico-legal autopsy cases. The dataset comprised 166 cases from Finland over the period 2016-2023. The diagnosis of AI was based on β-APP stain (TAI, VAI, or no AI). Data on background characteristics and neuropathology findings were collected from cause-of-death investigation documents. Prevalence ratios were calculated for each variable to enable comparisons between the AI categories. The sample were 71.7% males; median age was 41 years (range 0-96). There were 26 cases with TAI, 44 with VAI, and 96 with no AI. The variables that showed statistical significance and had at least two-fold prevalence among TAI cases compared to VAI cases were: a documented recent injury; and presence of any extracranial/cranial/intracranial injury (including subdural haemorrhage [SDH], subarachnoid haemorrhage [SAH], intracerebral/ventricular haemorrhage [ICVH], or contusion) in autopsy or neuropathology. Correspondingly, variables indicating TAI over no AI were: a documented recent injury; postinjury survival ≥ 24h; and presence of any extracranial/cranial/intracranial injury (including SDH, SAH, ICVH, contusion), herniation, or infarction in autopsy or neuropathology. Postinjury survival < 30min was identified as an indicator of no AI over TAI. Finally, variables indicating VAI over no AI were: postinjury survival ≥ 24h; lack of external injury to the head; and presence of SDH, brain oedema, herniation, or infarction in autopsy or neuropathology. In conclusion, we report several differences in characteristics and findings between cases diagnosed with TAI, VAI, and no AI. Our findings may help estimate the likelihood and potential aetiology of AI based on background characteristics and other neuropathology findings.

Article Review : Peran Hipertensi terhadap Patomekanisme Stroke Iskemik dan Hemoragik

Stroke is a syndrome characterized by sudden focal neurological deficits caused by vascular injury, either hemorrhage or infarction in the central nervous system. According to the World Health Organization, approximately 15 million people experience stroke worldwide each year, with 5 million resulting in death and another 5 million suffering permanent disability. Hypertension is a major risk factor for both ischemic and hemorrhagic stroke, mediated by complex pathophysiological mechanisms. This review aims to explore the mechanisms by which hypertension contributes to the pathophysiology of stroke based on current evidence. The study adopts a literature review approach, utilizing data sources from journal articles, books, and other relevant documents accessible online via search engines such as Google Scholar®, PubMed®, and ScienceDirect®. The findings indicate that ischemic stroke occurs due to atherosclerosis and microvascular dysfunction induced by hypertension, whereas hemorrhagic stroke involves vessel rupture resulting from arterial wall weakening. Hypertension also affects the permeability of the blood-brain barrier through molecular pathways such as vascular endothelial growth factor (VEGF) release, leading to cerebral edema. Studies demonstrate that effective blood pressure control can significantly reduce the risk of stroke by up to 41%, underscoring hypertension as a primary target in stroke prevention.

Location-specific net water uptake and malignant cerebral edema in acute anterior circulation occlusion ischemic stroke.

Early identification of malignant cerebral edema (MCE) in patients with acute ischemic stroke is crucial for timely interventions. We aimed to identify regions critically associated with MCE using the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) to evaluate the association between location-specific-net water uptake (NWU) and MCE. This multicentre, retrospective cohort study included patients with acute ischemic stroke following large anterior circulation occlusion. The ASPECTS was determined by RAPID ASPECTS software. ASPECTS-NWU and Region-NWU were calculated automatically by comparing the Hounsfield units values in the ischemic and contralateral regions. Critical ASPECTS MCE regions and Region-NWU were evaluated by multivariate logistic regression and the areas under the receiver operating characteristic curves (AUCs). The study included 513 patients. Multivariate analysis showed that the ASPECTS insula (OR=2.49; 95% CI, 1.44-4.31) and M5 (OR=1.59; 95% CI, 1.11-3.41) regions were significantly associated with MCE. After adjustment, only the insula (OR=2.34; 95% CI, 1.23-4.45) was independently associated with MCE. Univariable ROC analysis found AUCs for Insula-NWU (AUC, 0.70; 95% CI, 0.65- 0.76)and ASPECTS-NWU (AUC, 0.64; 95% CI, 0.58-0.70) .The Insula-NWU had better diagnostic power than ASPECTS-NWU (DeLong test; P=0.01). A multivariate regression model that combined the NIHSS, ASPECTS, insula involvement, and Insula-NWU had good discriminatory power (AUC=0.80; 95% CI, 0.74-0.86) and better diagnostic power than Insula-NWU (DeLong test; P<0.01). Brief statement directed to the stated purpose or hypothesis; no references should be cited.The insula region is critical for MCE, and Insula-NWU has better prediction efficacy than ASPECTS-NWU. This method does not rely on advanced imaging, facilitating rapid assessment in emergencies. ASPECTS = the Alberta Stroke Program Early Computed Tomography Score; AUC= the areas under the receiver operating characteristic curve; CT=computed tomography; CTP=CT perfusion; HU = hounsfield unit; MCE = malignant cerebral edema; NCCT=non-contrast Computed Tomography; NWU = net water uptake; ROC = receiver operating characteristic curve.

Severe Diabetic Ketoacidosis in Children with Type 1 Diabetes: Ongoing Challenges in Care.

Diabetic ketoacidosis is the most common acute complication in children and adolescents with type 1 diabetes, and contributes significantly to morbidity, mortality, and healthcare burden. This review aims to explore the multifaceted aspects of severe diabetic ketoacidosis in pediatric age, including its epidemiology, pathogenesis, risk factors, complications and emphasizing advances in prevention strategies. Incidence rates vary due to influences from geographic, socioeconomic, cultural and demographic factors. Pathogenesis is linked to insulin deficiency and an excess of counter-regulatory hormones, which disrupt glucose, protein, and lipid metabolism, causing hyperglycemia, ketosis, acidosis, dehydration, and electrolyte imbalances. According to the International Society for Pediatric and Adolescent Diabetes guidelines, severe diabetic ketoacidosis is characterized by a pH < 7.1 or bicarbonate < 5 mmol/L. This condition can lead to a wide range of life-threatening complications, including cerebral edema that represents the leading cause of death. Several prevention strategies, including awareness campaigns, early diagnosis of diabetes, regular monitoring and management, effective insulin therapy, education, access to healthcare and technological assistance, may contribute to reduce the risk of severe diabetic ketoacidosis episodes in children and adolescents.

Nanoparticle-in-Hydrogel Delivery System for the Sequential Release of Two Drugs.

Glioblastoma is the most common and lethal primary brain tumor. Patients often suffer from tumor- and treatment induced vasogenic edema, with devastating neurological consequences. Intracranial edema is effectively treated with dexamethasone. However, systemic dexamethasone requires large doses to surpass the blood brain barrier in therapeutic quantities, which is associated with significant side effects. The aim of this study was to investigate a biodegradable, dextran-hydroxyethyl methacrylate (dex-HEMA) based hydrogel, containing polymeric micelles loaded with dexamethasone and liposomes encapsulating dexamethasone phosphate for localized and prolonged delivery. Poly(ethylene glycol)-b-poly(N-2-benzoyloxypropyl methacrylamide (mPEG-b-p(HPMA-Bz)) micelles were loaded with dexamethasone and characterized. The dexamethasone micelles, together with dexamethasone phosphate liposomes, were dispersed in an aqueous dex-HEMA solution followed by radical polymerization using a photoinitiator in combination with light. The kinetics and mechanisms of drug release from this hydrogel were determined. The diameter of the nanoparticles was larger than the mesh size of the hydrogel, rendering them immobilized in the polymer network. The micelles immediately released free dexamethasone from the hydrogel for two weeks. The dexamethasone phosphate loaded in the liposomes was not released until the gel degraded and intact liposomes were released, starting after 15 days. The different modes of release result in a biphasic and sequential release profile of dexamethasone followed by dexamethasone phosphate liposomes. The results show that this hydrogel system loaded with both dexamethasone polymeric micelles and dexamethasone phosphate loaded liposomes has potential as a local delivery platform for the sequential release of dexamethasone and dexamethasone phosphate, for the intracranial treatment of glioblastoma associated edema.

Effects of blood pressure lowering in patients treated with intravenous thrombolysis before endovascular thrombectomy.

The effects of blood pressure (BP) lowering in patients treated with intravenous tissue plasminogen activator (IV tPA) before endovascular thrombectomy (EVT) are unclear. This study aims to investigate whether intensive and conventional BP management affect outcomes differently, depending on IV tPA administration before EVT. In this subgroup analysis of the Outcome in Patients Treated with Intra-Arterial Thrombectomy-Optimal Blood Pressure Control (OPTIMAL-BP; ClinicalTrials.gov Identifier: NCT04205305) trial, patients were divided into groups based on IV tPA use before EVT. Clinical outcomes of intensive (systolic BP target <140 mm Hg) or conventional BP management (systolic BP target 140-180 mm Hg) were compared among group. The primary efficacy outcome was a favorable outcome at 3 months (modified Rankin Scale score of 0-2). Primary safety outcomes included symptomatic intracerebral hemorrhage (sICH) within 36 hours and stroke-related death within 3 months. Among the 302 patients, the IV tPA group included 98 (32.5%) and the non-IV tPA group comprised 204 subjects (67.5%). In the IV tPA group, intensive BP management significantly lowered the favorable outcome rate (intensive, 27.3% vs. conventional, 51.9%; adjusted odds ratio [aOR], 0.36; 95% confidence interval [CI], 0.13-0.93; p = 0.04). In the non-IV tPA group, the risk difference rate of favorable outcome was not significantly different between intensive and conventional BP management (44.1% vs. 55.9%; aOR, 0.62; 95% CI, 0.31-1.22; p = 0.17). Notably, the proportion of malignant cerebral edema within 36 hours in the IV tPA group was significantly higher in the intensive management group (18.2%) than in the conventional management group (1.9%; aOR, 10.72; 95% CI, 1.24-92.29; p = 0.03). sICH and mortality rates were not significantly different between intensive and conventional BP management in either study groups. Intensive BP management worsen 3-month functional outcomes after successful EVT without reducing sICH among patients who received IV tPA before EVT, indicating that BP lowering in this population should be cautious.