Neutrophil-to-lymphocyte ratio on admission predicts early perihematomal edema growth after intracerebral hemorrhage.

Poor functional outcome is associated with perihematomal edema (PHE) expansion after intracerebral hemorrhage (ICH). The inflammatory response is crucial for the onset and progression of PHE. This study aimed to determine the connection between admission neutrophil-lymphocyte ratio (NLR) and early PHE development. We retrospectively analyzed patients with ICH admitted to the Chaohu Affiliated Hospital of Anhui Medical University from January 2021 to December 2022. The primary outcome measure was absolute PHE, defined as the volume of the follow-up PHE minus admission PHE. A semiautomated measurement tool (3D Slicer) was used to calculate the volumes of cerebral hematoma and cerebral edema. Spearman's correlation analysis determined the relationship between NLR and absolute PHE. The multiple linear regression model was constructed to analyze the predictive relation of admission NLR on early PHE expansion. A total of 117 patients were included. The median hematoma and PHE volumes on admission were 9.38 mL (interquartile range [IQR], 4.53-19.54) and 3.54 mL (IQR, 1.33-7.1), respectively. The median absolute PHE was 2.26 mL (IQR, 1.25-4.23), and the median NLR was 3.10 (IQR, 2.26-3.86). Spearman's correlation test showed a positive correlation between admission NLR and absolute PHE (r = .548, P < .001). Multiple linear regression analyses suggested that for every 1-unit increase in admission NLR (B = .176, SE = .043, Beta = .275, P < .001), there was a 0.176 mL increase in absolute PHE. Admission neutrophil-to-lymphocyte ratio (NLR) significantly and positively predicted early perihematomal edema (PHE) expansion.

A Case of Transient Hyperlactatemia Induced by Intravenous Glycerol Administration in a Patient With Brain Trauma.

Elevated lactate levels are associated with a poor prognosis in patients with sepsis and shock. Intravenous glycerol administration is often used in Japan to treat patients with acute stroke or brain trauma, but such treatment can cause elevated lactate levels. We experienced a case of transient hyperlactatemia induced by intravenous glycerol administration in a patient with brain trauma. A 74-year-old woman underwent decompressive craniotomy because of loss of consciousness and brain edema. Glycerol was administered after the operation for management of the brain edema. Although the patient's hemodynamics remained stable, her lactate level decreased and increased repeatedly. We recognized that the elevation in her lactate level was associated with the administration of intravenous glycerol. This case suggests that intravenous glycerol administration can induce transient hyperlactatemia.

Association between quantitative analysis of cerebral edema using CT imaging and neurological outcomes in cardiac arrest survivors.

BACKGROUND: To determine if the density distribution proportion of Hounsfield unit (HUdp) in head computed tomography (HCT) images can be used to quantitatively measure cerebral edema in survivors of out-of-hospital cardiac arrest (OHCA). METHODS: This retrospective observational study included adult comatose OHCA survivors who underwent HCT within 6 h (first) and 72-96 h (second), all performed using the same CT scanner. Semi-automated quantitative analysis was used to identify differences in HUdp at specific HU ranges across the intracranial component based on neurological outcome. Cerebral edema was defined as the increased displacement of the sum of HUdp values (ΔHUdp) at a specific range between two HCT scans. Poor neurological outcome was defined as cerebral performance categories 3-5 at 6 months after OHCA. RESULTS: Twenty-three (42%) out of 55 patients had poor neurological outcome. Significant HUdp differences were observed between good and poor neurological outcomes in the second HCT scan at HU = 1-14, 23-35, and 39-56 (all P < 0.05). Only the ΔHUdp = 23-35 range showed a significant increase and correlation in the poor neurological outcome group (4.90 vs. -0.72, P < 0.001) with the sum of decreases in the other two ranges (r = 0.97, P < 0.001). Multivariate logistic regression analysis demonstrated a significant association between ΔHUdp = 23-35 range and poor neurological outcomes (adjusted OR, 1.12; 95% CI: 1.02-1.24; P = 0.02). CONCLUSION: In this cohort study, the increased displacement in ΔHUdp = 23-35 range is independently associated with poor neurological outcome and provides a quantitative assessment of cerebral edema formation in OHCA survivors.

The potential role of mechanotransduction in the management of pediatric calvarial bone flap repair.

Pediatric patients suffering traumatic brain injuries may require a decompressive craniectomy to accommodate brain swelling by removing a portion of the skull. Once the brain swelling subsides, the preserved calvarial bone flap is ideally replaced as an autograft during a cranioplasty to restore protection of the brain, as it can reintegrate and grow with the patient during immature skeletal development. However, pediatric patients exhibit a high prevalence of calvarial bone flap resorption post-cranioplasty, causing functional and cosmetic morbidity. This review examines possible solutions for mitigating pediatric calvarial bone flap resorption by delineating methods of stimulating mechanosensitive cell populations with mechanical forces. Mechanotransduction plays a critical role in three main cell types involved with calvarial bone repair, including mesenchymal stem cells, osteoblasts, and dural cells, through mechanisms that could be exploited to promote osteogenesis. In particular, physiologically relevant mechanical forces, including substrate deformation, external forces, and ultrasound, can be used as tools to stimulate bone repair in both in vitro and in vivo systems. Ultimately, combating pediatric calvarial flap resorption may require a combinatorial approach using both cell therapy and bioengineering strategies.

Metabolic crisis in maple syrup urine disease: an unusual complication of a rare disease: a case report.

A 19-year-old woman with known maple syrup urine disease presented to hospital with metabolic crisis in the setting of influenza type A infection and intractable vomiting, rapidly progressing to acute cerebral oedema manifesting as refractory seizures and decreased level of consciousness needing emergency intubation and mechanical ventilation, continuous veno-venous haemodiafiltration and thiopentone coma. A computed tomography scan and magnetic resonance imaging of the brain demonstrated classic signs of cerebral oedema secondary to a metabolic crisis from the metabolic disorder. Her management posed multiple challenges to all teams involved due to lack of familiarity and experience in managing this clinical scenario in the adult intensive care setting.

Clinical Trial Protocol for BEACH: A Phase 2a Study of MW189 in Patients with Acute Nontraumatic Intracerebral Hemorrhage.

Patients with acute spontaneous intracerebral hemorrhage (ICH) develop secondary neuroinflammation and cerebral edema that can further damage the brain and lead to increased risk of neurologic complications. Preclinical studies in animal models of acute brain injury have shown that a novel small-molecule drug candidate, MW01-6-189WH (MW189), decreases neuroinflammation and cerebral edema and improves functional outcomes. MW189 was also safe and well tolerated in phase 1 studies in healthy adults. The proof-of-concept phase 2a Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH) clinical trial is a first-in-patient, multicenter, randomized, double-blind, placebo-controlled trial. It is designed to determine the safety and tolerability of MW189 in patients with acute ICH, identify trends in potential mitigation of neuroinflammation and cerebral edema, and assess effects on functional outcomes. A total of 120 participants with nontraumatic ICH will be randomly assigned 1:1 to receive intravenous MW189 (0.25 mg/kg) or placebo (saline) within 24 h of symptom onset and every 12 h for up to 5 days or until hospital discharge. The 120-participant sample size (60 per group) will allow testing of the null hypothesis of noninferiority with a tolerance limit of 12% and assuming a "worst-case" safety assumption of 10% rate of death in each arm with 10% significance and 80% power. The primary outcome is all-cause mortality at 7 days post randomization between treatment arms. Secondary end points include all-cause mortality at 30 days, perihematomal edema volume after symptom onset, adverse events, vital signs, pharmacokinetics of MW189, and inflammatory cytokine concentrations in plasma (and cerebrospinal fluid if available). Other exploratory end points are functional outcomes collected on days 30, 90, and 180. BEACH will provide important information about the utility of targeting neuroinflammation in ICH and will inform the design of future larger trials of acute central nervous system injury.

Potentiating glymphatic drainage minimizes post-traumatic cerebral oedema.

Cerebral oedema is associated with morbidity and mortality after traumatic brain injury (TBI)1. Noradrenaline levels are increased after TBI2-4, and the amplitude of the increase in noradrenaline predicts both the extent of injury5 and the likelihood of mortality6. Glymphatic impairment is both a feature of and a contributor to brain injury7,8, but its relationship with the injury-associated surge in noradrenaline is unclear. Here we report that acute post-traumatic oedema results from a suppression of glymphatic and lymphatic fluid flow that occurs in response to excessive systemic release of noradrenaline. This post-TBI adrenergic storm was associated with reduced contractility of cervical lymphatic vessels, consistent with diminished return of glymphatic and lymphatic fluid to the systemic circulation. Accordingly, pan-adrenergic receptor inhibition normalized central venous pressure and partly restored glymphatic and cervical lymphatic flow in a mouse model of TBI, and these actions led to substantially reduced brain oedema and improved functional outcomes. Furthermore, post-traumatic inhibition of adrenergic signalling boosted lymphatic export of cellular debris from the traumatic lesion, substantially reducing secondary inflammation and accumulation of phosphorylated tau. These observations suggest that targeting the noradrenergic control of central glymphatic flow may offer a therapeutic approach for treating acute TBI.

Live donor liver transplantation for pediatric acute liver failure: challenges and outcomes.

OBJECTIVE: This study aimed at studying the challenges and outcomes of live-donor liver transplantation (LDLT) for pediatric acute liver failure (PALF). STUDY DESIGN: A total of 315 patients with PALF were treated over a period of 11 years. 42 underwent LT (41 LDLT and one DDLT), constituting 38% (41/110) of all pediatric transplants during this duration. The outcomes of LDLT for PALF were analyzed. RESULTS: All the 41 children who underwent LT met the Kings College criteria (KCC). The etiology was indeterminate in 46.3% (n = 19) children. 75.6% (n = 31) were on mechanical ventilation for grade 3/4 hepatic encephalopathy. There was presence of cerebral edema on a computed tomography scan of the brain in 50% of the children. One-third of our children required hemodynamic support with vasopressors. Systemic inflammatory response syndrome and sepsis were observed in 46.3% and 41.4% of patients, respectively. Post-LDLT 1- and 5-yr patient and graft survival were 75.6% and 70.9%, respectively. The survival in children satisfying KCC but did not undergo LT was 24% (38/161). Vascular and biliary complication rates were 2.4% and 4.8%, respectively. No graft loss occurred because of acute rejection. In multivariate analysis, pre-LT culture positivity and cerebral edema, persistence of brain edema after transplantation, and resultant pulmonary complications were significantly associated with post-LT death. Thirteen (32%) children who underwent plasmapheresis prior to LT had better post-LT neurological recovery, as evidenced by early extubation. CONCLUSION: LDLT for PALF is lifesaving and provides a unique opportunity to time transplantation. Good long-term survival can be achieved, despite the majority of patients presenting late for transplantation. Early referral and better selection can save more lives through timely transplantation.

Gas6 Exerts Neuroprotective Effects via Restoring the Blood-Brain Barrier in Mice with Sepsis-Associated Encephalopathy.

OBJECTIVE: Sepsis-associated encephalopathy (SAE), characterized by cognitive and emotional impairments, is not well investigated in sepsis survivors. Growth arrest-specific gene 6 (Gas6) has been extensively used to treat cerebral diseases. This study aimed to evaluate the neuroprotective effects of Gas6 in post-septic mice and to determine the underlying mechanisms of action. METHODS: Mice underwent cecal ligation and puncture (CLP) for sepsis induction. Mice were then immediately injected with 6 µg of Gas6 via the tail vein, and the effect was evaluated after 24 hours. The neurological severity score (NSS) was used to assess neurological deficits in post-septic mice. In addition, brain edema was evaluated by measuring the brain water content and blood-brain barrier (BBB) permeability using Evans blue (EB) dye extravasation. Western blotting and immunofluorescence assays were performed to determine the expression of tight junction (TJ)-associated proteins such as occludin and zonula occludens-1 (ZO-1). RESULTS: Post-septic mice exhibited increased NSS, brain edema, and BBB permeability. However, acute Gas6 treatment attenuated the severe effects of sepsis on neurologic function in mice. Therefore, Gas6 attenuates brain edema and restores BBB permeability. These findings suggest that Gas6 could alleviate neurological deficits, brain edema, BBB damage, and reverse the decreased expression of occludin and ZO-1 in the brain tissue to protect against SAE. CONCLUSION: Gas6 protects against SAE by restoring the impaired BBB permeability.

Peritoneal dialysis in the setting of acute brain injury: an underappreciated modality.

INTRODUCTION: Dialysis is complicated in the setting of acute brain injury (ABI) due to several factors including acute solute shifts, acid base changes, need for anticoagulation, and changes in intracranial pressure. For these reasons, continuous renal replacement therapy (CRRT) is often the chosen modality for renal replacement needs in these patients. Peritoneal dialysis (PD) is less discussed but shares many of the benefits often attributed to CRRT. We describe, from both nephrology and neurosurgical perspectives, a case successfully managed with PD. CASE: A 25-year-old male with history of end-stage kidney disease (ESKD) secondary to focal segmental glomerulosclerosis on continuous cycling PD for 5 years presented to the hospital with headache and altered mental status. Initial imaging revealed a large intraventricular hemorrhage extending to the fourth ventricle. He underwent an emergent right depressive hemicraniectomy and clot evacuation. Post-operative imaging revealed worsening cerebral edema, intraventricular hemorrhage, and hydrocephalus. The decision was made to continue PD, noting that it retains many of the benefits of CRRT (which it is in fact, a form of) which he tolerated well until the need for a percutaneous gastrostomy tube arose. He was transiently transitioned to hemodialysis but returned to PD once his gastrostomy healed. He continued PD for 1 year without complication and eventually received a kidney transplant. DISCUSSION: In managing patients with ABI undergoing dialysis, a number of considerations must be undertaken including avoidance of hypotension to maintain cerebral perfusion pressure and minimize ischemia reperfusion injury, avoidance of anticoagulants that can precipitate or worsen bleeding, the potential for cerebral edema due to rapid solute clearance and osmotic dissipation of therapeutic hypernatremia, and the mitigation of intracellular acidosis from bicarbonate delivery. Although underutilized, PD may potentially serve as a viable option for dialysis in the setting of ABI as demonstrated by the case presented.

Prospective Analysis of Cerebral Edema Admission and Clinical Outcome in Ruptured Intracranial Aneurysm.

AIM: To evaluate the association between global cerebral edema (GCE) after subarachnoid hemorrhage (SAH) and its impact on functional outcome evaluated by the modified Rankin scale (mRS). MATERIAL AND METHODS: This is a prospective cohort study with patients who were admitted to the hospital due to SAH. During the period from January 2018 to November 2019, 107 patients with intracranial aneurysms were enrolled. Using univariate and multivariate analysis, we sought to identify predictors and evaluated the impact of GCE on outcome after 6 months using the mRS. RESULTS: GCE was present in 54 (50.5%) patients, of which 27 (25.2%) were mild, 20 (18.7%) moderate and 7 (6.5%) were severe. Univariate analysis identified high Hunt-Hess and Glasgow coma scale on clinical admission as predictors factors of GCE (p < 0.05), and higher modified Fisher scale as a radiological predictor of Glasgow coma scale (p < 0.05). Thirty-three (30.8%) patients were deceased at 6 months. Death or severe disability were predicted by higher age, poor clinical scale on admission and severe GCE (p < 0.05). CONCLUSION: GCE on admission is independently associated with poor clinical outcomes at discharge, and six months after SAH. Given its strong association with poor clinical grade on admission, GCE should be considered a straightforward and radiological important marker of early brain injury, with ominous implications.

Intracranial Pressure Monitoring and Management in Aneurysmal Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage is a medical condition that can lead to intracranial hypertension, negatively impacting patients' outcomes. This review article explores the underlying pathophysiology that causes increased intracranial pressure (ICP) during hospitalization. Hydrocephalus, brain swelling, and intracranial hematoma could produce an ICP rise. Although cerebrospinal fluid withdrawal via an external ventricular drain is commonly used, ICP monitoring is not always consistently practiced. Indications for ICP monitoring include neurological deterioration, hydrocephalus, brain swelling, intracranial masses, and the need for cerebrospinal fluid drainage. This review emphasizes the importance of ICP monitoring and presents findings from the Synapse-ICU study, which supports a correlation between ICP monitoring and treatment with better patient outcomes. The review also discusses various therapeutic strategies for managing increased ICP and identifies potential areas for future research.

Outcomes in Patients with Aneurysmal Subarachnoid Hemorrhage Receiving Sulfonylureas: A Propensity-Adjusted Analysis.

OBJECTIVE: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with increased blood-brain barrier permeability, disrupted tight junctions, and increased cerebral edema. Sulfonylureas are associated with reduced tight-junction disturbance and edema and improved functional outcome in aSAH animal models, but human data are scant. We analyzed neurological outcomes in aSAH patients prescribed sulfonylureas for diabetes mellitus. METHODS: Patients treated for aSAH at a single institution (August 1, 2007-July 31, 2019) were retrospectively reviewed. Patients with diabetes were grouped by presence or absence of sulfonylurea therapy at hospital admission. The primary outcome was favorable neurologic status at last follow-up (modified Rankin Scale score ≤2). Variables with an unadjusted P-value of <0.20 were included in a propensity-adjusted multivariable logistic regression analysis to identify predictors of favorable outcomes. RESULTS: Of 1013 aSAH patients analyzed, 129 (13%) had diabetes at admission, and 16 of these (12%) were receiving sulfonylureas. Fewer diabetic than nondiabetic patients had favorable outcomes (40% [52/129] vs. 51% [453/884], P = 0.03). Among diabetic patients, sulfonylurea use (OR 3.90, 95% CI 1.05-15.9, P = 0.046), Charlson Comorbidity Index <4 (OR 3.66, 95% CI 1.24-12.1, P = 0.02), and absence of delayed cerebral infarction (OR 4.09, 95% CI 1.20-15.5, P = 0.03) were associated with favorable outcomes in the multivariable analysis. CONCLUSIONS: Diabetes was strongly associated with unfavorable neurologic outcomes. An unfavorable outcome in this cohort was mitigated by sulfonylureas, supporting some preclinical evidence of a possible neuroprotective role for these medications in aSAH. These results warrant further study on dose, timing, and duration of administration in humans.

Safety of peripheral 3% hypertonic saline bolus administration for neurologic emergency.

BACKGROUND/OBJECTIVE: Hypertonic sodium chloride (HTS) is used for emergent treatment of acute cerebral edema and other neurologic emergencies. Central access is not commonly available in emergent situations and 3% HTS is utilized peripherally. Many studies have shown the safety of its administration at rates up to 75 mL/h, but there is a lack of data to establish the safety of peripherally administered, rapid bolus dosing in emergent situations. The objective of this study is to describe the safety of rapid, peripherally administered (≥ 250 mL/h) 3% HTS for neurologic emergencies. METHODS: This is a retrospective, cohort study including adult patients receiving 3% HTS via a peripheral IV site for elevated intracranial pressure, cerebral edema, or other neurological emergencies at a rate of at least 250 m/h between May 5, 2018 - September 30, 2021. Patients were excluded if they simultaneously received another hypertonic saline fluid. Baseline characteristics collected included HTS dose, rate and site of administration, indication for use and patient demographics. The primary safety outcome was incidence of extravasation and phlebitis within one hour of HTS administration. RESULTS: There were 206 patients receiving 3% HTS who were screened, and 37 patients met inclusion criteria. The most common reason for exclusion was administration at a rate < 250 m/h. The median age was 60 (IQR 45, 72) with 51.4% being male. The most common indications for HTS were traumatic brain injury (45.9%) and intracranial hemorrhage (37.8%). The most common administration location was the emergency department (78.4%). The median IV-gauge (n = 29) was 18 (IQR 18, 20), with the most common placement site being antecubital (48.6%). The median dose of HTS was 250 mL (IQR 250, 350), with a median administration rate of 760 mL/h (IQR 500, 999). There were no episodes of extravasation or phlebitis noted. CONCLUSIONS: Rapid, peripheral administration of 3% HTS boluses is a safe alternative for treatment of neurologic emergencies. Administration at rates up to 999 mL/h did not result in extravasation or phlebitis.

[Dysnatremia]. / Dysnatriämien.

Changes in serum sodium concentrations are frequently encountered by anesthesiologists, are complex and are often inadequately treated. Feared consequences include neurological complications, such as cerebral hemorrhage, cerebral edema and coma. Dysnatremia is always accompanied disturbances in the water balance. Accordingly, these are routinely classified based on the tonicity; however, in the daily routine and especially in the acute setting, the volume status and extracellular volume are often difficult to assess. Severe symptomatic hyponatremia with impending cerebral edema is treated by administration of hypertonic saline solution. If the rise in serum sodium is too rapid, there is a risk of central pontine myelinolysis. In a second step, the cause of the hyponatremia can be investigated and the appropriate treatment can be initiated. In the case of hypernatremia, the etiology of the disorder must be clarified before treatment. The goal is to compensate for the water deficiency by correcting the cause, specific volume therapy and, if necessary, drug support. A slow and controlled compensation must be closely monitored in order to avoid neurological complications. An algorithm has been developed that provides an overview of the dysnatremias, aids with making the diagnosis and gives recommendations for treatment measures in the clinical routine.

Correlations of intracranial pathology and cause of head injury with retinal hemorrhage in infants and toddlers: A multicenter, retrospective study by the J-HITs (Japanese Head injury of Infants and Toddlers study) group.

INTRODUCTION: In infants who have suffered head trauma there are two possible explanations for retinal hemorrhage (RH): direct vitreous shaking and occurrence in association with intracranial lesions. Which possibility is more plausible was examined. MATERIAL AND METHODS: This multicenter, retrospective study reviewed the clinical records of children younger than four years with head trauma who had been diagnosed with any findings on head computed tomography (CT) and/or magnetic resonance imaging (MRI). Of 452 cases, 239 underwent an ophthalmological examination and were included in this study. The relationships of RH with intracranial findings and the cause of injury were examined. RESULT: Odds ratios for RH were significant for subdural hematoma (OR 23.41, p = 0.0004), brain edema (OR 5.46, p = 0.0095), nonaccidental (OR 11.26, p<0.0001), and self-inflicted falls (OR 6.22, p = 0.0041). CONCLUSION: Although nonaccidental, brain edema and self-inflicted falls were associated with RH, subdural hematoma was most strongly associated with RH.

Acute kidney injury in neurocritical patients: a retrospective cohort study.

BACKGROUND /OBJECTIVE: Acute kidney injury (AKI) is a significant complication in critical care units (CCU). Non-neurological complications such as AKI are an independent predictor of poor clinical outcomes, with an increase in morbidity and mortality, financial costs, and worse functional recovery. This work aims to estimate the incidence of AKI and evaluate the risk factors and complications of AKI in neurocritical patients hospitalized in the CCU. METHODS: A retrospective cohort study was conducted. Patients admitted to the neurocritical care unit between 2016 and 2018 with a stay longer than 48 h were retrospectively analyzed in regard to the incidence, risk factors, and outcomes of AKI. RESULTS: The study population comprised 213 neurocritical patients. The incidence of AKI was 23.5%, with 58% KDIGO 1 and 2% requiring renal replacement therapy. AKI was an independent predictor of prolonged use of mechanical ventilation, cerebral edema, and mortality. Cerebral edema [OR 4.40 (95% CI 1.98-9.75) p < 0.001] and a change in chloride levels greater than 4 mmol/L at 48 h (OR 2.44 (95% CI 1.10-5.37) p = 0.027) were risk factors for developing AKI in the first 14 days of hospitalization. CONCLUSION: There is a high incidence of AKI in neurocritical patients; it is associated with worse clinical outcomes regardless of the CCU admission etiology or AKI severity.

Augmenting hematoma-scavenging capacity of innate immune cells by CDNF reduces brain injury and promotes functional recovery after intracerebral hemorrhage.

During intracerebral hemorrhage (ICH), hematoma formation at the site of blood vessel damage results in local mechanical injury. Subsequently, erythrocytes lyse to release hemoglobin and heme, which act as neurotoxins and induce inflammation and secondary brain injury, resulting in severe neurological deficits. Accelerating hematoma resorption and mitigating hematoma-induced brain edema by modulating immune cells has potential as a novel therapeutic strategy for functional recovery after ICH. Here, we show that intracerebroventricular administration of recombinant human cerebral dopamine neurotrophic factor (rhCDNF) accelerates hemorrhagic lesion resolution, reduces peri-focal edema, and improves neurological outcomes in an animal model of collagenase-induced ICH. We demonstrate that CDNF acts on microglia/macrophages in the hemorrhagic striatum by promoting scavenger receptor expression, enhancing erythrophagocytosis and increasing anti-inflammatory mediators while suppressing the production of pro-inflammatory cytokines. Administration of rhCDNF results in upregulation of the Nrf2-HO-1 pathway, but alleviation of oxidative stress and unfolded protein responses in the perihematomal area. Finally, we demonstrate that intravenous delivery of rhCDNF has beneficial effects in an animal model of ICH and that systemic application promotes scavenging by the brain's myeloid cells for the treatment of ICH.

Cerebral malaria-using the retina to study the brain.

Cerebral malaria (CM) remains a common cause of death of children in Africa with annual mortality of 400 000. Malarial retinopathy is a unique set of fundus signs which has diagnostic and prognostic value in CM. Assessment of malarial retinopathy is now widely utilised in clinical care, and routinely incorporated into clinical studies to refine entry criteria. As a visible part of the central nervous system, the retina provides insights into the pathophysiology of this infectious small-vessel vasculitis with adherent parasitised red blood cells. Fluorescein angiography and optical coherence tomography (OCT) have shown that patchy capillary non-perfusion is common and causes ischaemic changes in the retina in CM. It is likely this is mirrored in the brain and may cause global neurological impairments evident on developmental follow up. Three types of blood-retina barrier breakdown are evident: large focal, punctate, and vessel leak. Punctate and large focal leak (haemorrhage in formation) are associated with severe brain swelling and fatal outcome. Vessel leak and capillary non-perfusion are associated with moderate brain swelling and neurological sequelae. These findings imply that death and neurological sequelae have separate mechanisms and are not a continuum of severity. Each haemorrhage causes a temporary uncontrolled outflow of fluid into the tissue. The rapid accumulation of haemorrhages, as evidenced by multiple focal leaks, is a proposed mechanism of severe brain swelling, and death. Current studies aim to use optic nerve head OCT to identify patients with severe brain swelling, and macula OCT to identify those at risk of neurological sequelae.

Do animal models of brain tumors replicate human peritumoral edema? a systematic literature search.

INTRODUCTION: Brain tumors cause morbidity and mortality in part through peritumoral brain edema. The current main treatment for peritumoral brain edema are corticosteroids. Due to the increased recognition of their side-effect profile, there is growing interest in finding alternatives to steroids but there is little formal study of animal models of peritumoral brain edema. This study aims to summarize the available literature. METHODS: A systematic search was undertaken of 5 literature databases (Medline, Embase, CINAHL, PubMed and the Cochrane Library). The generic strategy was to search for various terms associated with "brain tumors", "brain edema" and "animal models". RESULTS: We identified 603 reports, of which 112 were identified as relevant for full text analysis that studied 114 peritumoral brain edema animal models. We found significant heterogeneity in the species and strain of tumor-bearing animals, tumor implantation method and edema assessment. Most models did not produce appreciable brain edema and did not test for observable manifestations thereof. CONCLUSION: No animal model currently exists that enable the investigation of novel candidates for the treatment of peritumoral brain edema. With current interest in alternative treatments for peritumoral brain edema, there is an unmet need for clinically relevant animal models.