Search

The use of drains, including suction drains in neurosurgery is individual preference-based, rather than scientific evidence-based. Furthermore, the use of suction drains has been associated with significant risks to patients, including sudden death. We present 2 cases of unfortunate sudden deaths following uneventful cranioplasty procedures, both of which were associated with the use of a suction drain. We also review the literature focusing on the benefits and risks in the use of suction drains, and discuss pathophysiological mechanisms underlying sudden death associated with their use. There is no substantial evidence to support the use of suction drains in neurosurgery. Furthermore, they have been associated with significant complications, including risk to life. Our experience and literature review suggest that the risk of sudden death is disproportionately higher following cranioplasty. We do not recommend the use of suction drains in cranial neurosurgery, and we strongly recommend against their use in cranioplasty procedures. [ABSTRACT FROM AUTHOR]

In human stroke, brain swelling is an important predictor of neurological outcome and mortality, yet treatments to reduce or prevent brain swelling are extremely limited, due in part to an inadequate understanding of mechanisms. In preclinical studies on cerebroprotection in animal models of stroke, historically, the focus has been on reducing infarct size, and in most studies, a reduction in infarct size has been associated with a corresponding reduction in brain swelling. Unfortunately, such findings on brain swelling have little translational value for treating brain swelling in patients with stroke. This is because, in humans, brain swelling usually becomes evident, either symptomatically or radiologically, days after the infarct size has stabilized, requiring that the prevention or treatment of brain swelling target mechanism(s) that are independent of a reduction in infarct size. In this problematizing review, we highlight the often-neglected concept that brain edema and brain swelling are not simply secondary, correlative phenomena of stroke but distinct pathological entities with unique molecular and cellular mechanisms that are worthy of direct targeting. We outline the advances in approaches for the study of brain swelling that are independent of a reduction in infarct size. Although straightforward, the approaches reviewed in this study have important translational relevance for identifying novel treatment targets for post-ischemic brain swelling. [ABSTRACT FROM AUTHOR]

Cerebral edema, characterized by abnormal fluid accumulation in brain tissue leading to increased intracranial pressure, poses significant challenges for anesthesiologists. This review delves into the pathophysiology, clinical manifestations, diagnostic approaches, pharmacological strategies, and anesthesiological considerations associated with cerebral edema. Disruptions in the blood-brain barrier, alterations in cerebral blood flow, cellular swelling, and aquaporin dysregulation contribute to the complexity of cerebral edema. Clinical presentations vary, encompassing cognitive changes, seizures, and neurological deficits. Accurate diagnosis relies on clinical assessments and neuroimaging, with MRI and CT scans playing pivotal roles. Pharmacological interventions, including osmotic agents, corticosteroids, diuretics, and barbiturates, target specific causes and symptoms. Anesthesiological challenges encompass ICP monitoring, choice of anesthetic agents, maintenance of cerebral perfusion, fluid management, temperature control, and collaboration with neurosurgical teams. This multidisciplinary approach ensures optimal patient care and emphasizes ongoing research collaboration for refining therapeutic strategies. This comprehensive review provides valuable insights for clinicians managing cerebral edema, offering a roadmap for tailored interventions and highlighting the need for continued advancements in understanding and treating this critical condition. Material and method: The literature review applied standard criteria and focused on PubMed articles using keywords: cerebral edema, pathophysiology, aquaporin, blood-brain barrier, anesthesiology, cerebral edema treatment, corticosteroids. [ABSTRACT FROM AUTHOR]

Cerebral edema, characterized by abnormal fluid accumulation in brain tissue leading to increased intracranial pressure, poses significant challenges for anesthesiologists. This review delves into the pathophysiology, clinical manifestations, diagnostic approaches, pharmacological strategies, and anesthesiological considerations associated with cerebral edema. Disruptions in the blood-brain barrier, alterations in cerebral blood flow, cellular swelling, and aquaporin dysregulation contribute to the complexity of cerebral edema. Clinical presentations vary, encompassing cognitive changes, seizures, and neurological deficits. Accurate diagnosis relies on clinical assessments and neuroimaging, with MRI and CT scans playing pivotal roles. Pharmacological interventions, including osmotic agents, corticosteroids, diuretics, and barbiturates, target specific causes and symptoms. Anesthesiological challenges encompass ICP monitoring, choice of anesthetic agents, maintenance of cerebral perfusion, fluid management, temperature control, and collaboration with neurosurgical teams. This multidisciplinary approach ensures optimal patient care and emphasizes ongoing research collaboration for refining therapeutic strategies. This comprehensive review provides valuable insights for clinicians managing cerebral edema, offering a roadmap for tailored interventions and highlighting the need for continued advancements in understanding and treating this critical condition. Material and method: ​​ The literature review applied standard criteria and focused on PubMed articles using keywords: cerebral edema, pathophysiology, aquaporin, blood-brain barrier, anesthesiology, cerebral edema treatment, corticosteroids

Brain swelling is a major cause of death and disability in ischemic stroke. Drugs of the gliflozin class, which target the Na+-coupled D-glucose cotransporter, SGLT2, are approved for type 2 diabetes mellitus (T2DM) and may be beneficial in other conditions, but data in cerebral ischemia are limited. We studied murine models of cerebral ischemia with middle cerebral artery occlusion/reperfusion (MCAo/R). Slc5a2/SGLT2 mRNA and protein were upregulated de novo in astrocytes. Live cell imaging of brain slices from mice following MCAo/R showed that astrocytes responded to modest increases in D-glucose by increasing intracellular Na+ and cell volume (cytotoxic edema), both of which were inhibited by the SGLT2 inhibitor, canagliflozin. The effect of canagliflozin was studied in three mouse models of stroke: non-diabetic and T2DM mice with a moderate ischemic insult (MCAo/R, 1/24 h) and non-diabetic mice with a severe ischemic insult (MCAo/R, 2/24 h). Canagliflozin reduced infarct volumes in models with moderate but not severe ischemic insults. However, canagliflozin significantly reduced hemispheric swelling and improved neurological function in all models tested. The ability of canagliflozin to reduce brain swelling regardless of an effect on infarct size has important translational implications, especially in large ischemic strokes. [ABSTRACT FROM AUTHOR]

Aim. To analyze and determine the optimal indications for microsurgical operative interventions in the shortest possible time from the subarachnoid hemorrhage onset to prevent anterior communicating artery (AcomA) aneurysm re-rupture and bleeding. Materials and methods. 280 patients with brain aneurysms were examined at the Uzhhorod Regional Center of Neurosurgery and Neurology and the City Hospital of Urgent and Emergency Medical Care under Zaporizhzhia City Council. Among them, 98 patients (48 males and 50 females) were diagnosed with AcomA aneurysms. The age of patients with AcomA aneurysms was from 20 to 72 years (mean age 47.8 ± 11.0 years). Aneurysms were verified using head and neck computed tomography angiography (a Toshiba Astelion scanner, 2016, No. 4СС162106), selective cerebral angiography (an angiography system General Energy Optima IGS 330, 2019, No. 80071260314), and brain magnetic resonance angiography (an i_Open 0,36 T magnetic resonance tomograph, 2005, No. Toc102633006). Cerebral hemodynamics was assessed using transcranial dopplerography (“Philips HD7” ultrasound diagnostic system, 2014, No. 69935). Results. In the first three days after the onset of subarachnoid hemorrhage, 18 (18 %) patients were admitted with ruptured aneurysms of this location, 62 (62 %) within 4–8 days, 12 (12 %) patients within 9–14 days, later than 14 days – 6 (6 %). All 98 patients underwent microsurgical clipping of AcomA aneurysms. Due to severe cerebral edema, decompressive craniectomy was performed in two patients. The results of surgical treatment were evaluated according to the modified Rankin scale at the time of hospital discharge and were as follows: in 65 (65 %) patients – good; in 18 (18 %) – moderate disability; in 4 (4 %) – serious disability. 11 (11 %) patients died. Conclusions. The treatment outcomes in patients with ruptured AcomA aneurysms were significantly dependent on factors related to increased risk of re-rupture: the presence of large-sized intracerebral hematoma, the aneurysm index exceeding 2, and multi-chamber aneurysm.

In the present paper, the forward problem of EEG and MEG is discussed, where the head is modeled by a spherical two-shell piecewise-homogeneous conductor with a neuronal current source positioned in the exterior shell area representing the brain tissue, while the interior shell portrays a cerebral edema. We consider constant conductivity, which assumes different values in each compartment, where the expansions of the electric potential and the magnetic field are represented via spherical harmonics. Furthermore, we demonstrate the reduction of our analytical results to the single-compartment model while it is shown that the magnetic field in the exterior of the conductor is a function only of the dipole moment and its position. Consequently, it does not depend on the inhomogeneity dictated by the interior shell, a fact that verifies the efficiency of the model. [ABSTRACT FROM AUTHOR]

No specific or adjunctive therapies exist to treat cerebral malaria (CM) as of date. CM is a neuropathological manifestation of the malaria infection in humans, caused by the hemoparasitic pathogen Plasmodium falciparum. Driven through a multitude of virulence factors, varied immune responses, variations in brain swelling with regard to the age of patients, parasite biomass, and parasite-typing, the essential pathogenetic mechanisms underlying clinical CM have remained elusive. However, a recent series of studies based on molecular, immunologic, and advanced neuroradiologic and machine-learning approaches have unraveled new trends and insights to better understand and focus on the key determinants of CM in humans. This could possibly be the beginning of the design of new and effective adjunctive therapies that may not be common or applicable to the entire malarious world, but that could, rather, be specific to the variations in the determinants of CM. [ABSTRACT FROM AUTHOR]

In human stroke, brain swelling is an important predictor of neurological outcome and mortality, yet treatments to reduce or prevent brain swelling are extremely limited, due in part to an inadequate understanding of mechanisms. In preclinical studies on cerebroprotection in animal models of stroke, historically, the focus has been on reducing infarct size, and in most studies, a reduction in infarct size has been associated with a corresponding reduction in brain swelling. Unfortunately, such findings on brain swelling have little translational value for treating brain swelling in patients with stroke. This is because, in humans, brain swelling usually becomes evident, either symptomatically or radiologically, days after the infarct size has stabilized, requiring that the prevention or treatment of brain swelling target mechanism(s) that are independent of a reduction in infarct size. In this problematizing review, we highlight the often-neglected concept that brain edema and brain swelling are not simply secondary, correlative phenomena of stroke but distinct pathological entities with unique molecular and cellular mechanisms that are worthy of direct targeting. We outline the advances in approaches for the study of brain swelling that are independent of a reduction in infarct size. Although straightforward, the approaches reviewed in this study have important translational relevance for identifying novel treatment targets for post-ischemic brain swelling.

Cerebral malaria (CM) remains a significant global health challenge with high morbidity and mortality. Malarial retinopathy has been shown to be diagnostically and prognostically significant in the assessment of CM. The major mechanism of death in paediatric CM is brain swelling. Long term morbidity is typically characterised by neurological and neurodevelopmental sequelae. Optical coherence tomography can be used to quantify papilloedema and macular ischaemia, identified as hyperreflectivity. Here we describe a protocol to test the hypotheses that quantification of optic nerve head swelling using optical coherence tomography can identify severe brain swelling in CM, and that quantification of hyperreflectivity in the macula predicts neurodevelopmental outcomes post-recovery. Additionally, our protocol includes the development of a novel, low-cost, handheld optical coherence tomography machine and artificial intelligence tools to assist in image analysis.

Brain swelling is a major cause of death and disability in ischemic stroke. Drugs of the gliflozin class, which target the Na+-coupled D-glucose cotransporter, SGLT2, are approved for type 2 diabetes mellitus (T2DM) and may be beneficial in other conditions, but data in cerebral ischemia are limited. We studied murine models of cerebral ischemia with middle cerebral artery occlusion/reperfusion (MCAo/R). Slc5a2/SGLT2 mRNA and protein were upregulated de novo in astrocytes. Live cell imaging of brain slices from mice following MCAo/R showed that astrocytes responded to modest increases in D-glucose by increasing intracellular Na+ and cell volume (cytotoxic edema), both of which were inhibited by the SGLT2 inhibitor, canagliflozin. The effect of canagliflozin was studied in three mouse models of stroke: non-diabetic and T2DM mice with a moderate ischemic insult (MCAo/R, 1/24 h) and non-diabetic mice with a severe ischemic insult (MCAo/R, 2/24 h). Canagliflozin reduced infarct volumes in models with moderate but not severe ischemic insults. However, canagliflozin significantly reduced hemispheric swelling and improved neurological function in all models tested. The ability of canagliflozin to reduce brain swelling regardless of an effect on infarct size has important translational implications, especially in large ischemic strokes.

In the present paper, the forward problem of EEG and MEG is discussed, where the head is modeled by a spherical two-shell piecewise-homogeneous conductor with a neuronal current source positioned in the exterior shell area representing the brain tissue, while the interior shell portrays a cerebral edema. We consider constant conductivity, which assumes different values in each compartment, where the expansions of the electric potential and the magnetic field are represented via spherical harmonics. Furthermore, we demonstrate the reduction of our analytical results to the single-compartment model while it is shown that the magnetic field in the exterior of the conductor is a function only of the dipole moment and its position. Consequently, it does not depend on the inhomogeneity dictated by the interior shell, a fact that verifies the efficiency of the model.

Background: When a patient arrives in the emergency department following a stroke, a traumatic brain injury, or sudden cardiac arrest, there is no therapeutic drug available to help protect their jeopardized neurons. One crucial reason is that we have not identified the molecular mechanisms leading to electrical failure, neuronal swelling, and blood vessel constriction in newly injured gray matter. All three result from a process termed spreading depolarization (SD). Because we only partially understand SD, we lack molecular targets and biomarkers to help neurons survive after losing their blood flow and then undergoing recurrent SD. Methods: In this review, we introduce SD as a single or recurring event, generated in gray matter following lost blood flow, which compromises the Na+/K+ pump. Electrical recovery from each SD event requires so much energy that neurons often die over minutes and hours following initial injury, independent of extracellular glutamate. Results: We discuss how SD has been investigated with various pitfalls in numerous experimental preparations, how overtaxing the Na+/K+ ATPase elicits SD. Elevated K+ or glutamate are unlikely natural activators of SD. We then turn to the properties of SD itself, focusing on its initiation and propagation as well as on computer modeling. Conclusions: Finally, we summarize points of consensus and contention among the authors as well as where SD research may be heading. In an accompanying review, we critique the role of the glutamate excitotoxicity theory, how it has shaped SD research, and its questionable importance to the study of early brain injury as compared with SD theory. [ABSTRACT FROM AUTHOR]

Background: Within 2 min of severe ischemia, spreading depolarization (SD) propagates like a wave through compromised gray matter of the higher brain. More SDs arise over hours in adjacent tissue, expanding the neuronal damage. This period represents a therapeutic window to inhibit SD and so reduce impending tissue injury. Yet most neuroscientists assume that the course of early brain injury can be explained by glutamate excitotoxicity, the concept that immediate glutamate release promotes early and downstream brain injury. There are many problems with glutamate release being the unseen culprit, the most practical being that the concept has yielded zero therapeutics over the past 30 years. But the basic science is also flawed, arising from dubious foundational observations beginning in the 1950s Methods: Literature pertaining to excitotoxicity and to SD over the past 60 years is critiqued. Results: Excitotoxicity theory centers on the immediate and excessive release of glutamate with resulting neuronal hyperexcitation. This instigates poststroke cascades with subsequent secondary neuronal injury. By contrast, SD theory argues that although SD evokes some brief glutamate release, acute neuronal damage and the subsequent cascade of injury to neurons are elicited by the metabolic stress of SD, not by excessive glutamate release. The challenge we present here is to find new clinical targets based on more informed basic science. This is motivated by the continuing failure by neuroscientists and by industry to develop drugs that can reduce brain injury following ischemic stroke, traumatic brain injury, or sudden cardiac arrest. One important step is to recognize that SD plays a central role in promoting early neuronal damage. We argue that uncovering the molecular biology of SD initiation and propagation is essential because ischemic neurons are usually not acutely injured unless SD propagates through them. The role of glutamate excitotoxicity theory and how it has shaped SD research is then addressed, followed by a critique of its fading relevance to the study of brain injury. Conclusions: Spreading depolarizations better account for the acute neuronal injury arising from brain ischemia than does the early and excessive release of glutamate. [ABSTRACT FROM AUTHOR]

• Early brain swelling is a hemodynamic problem. • In TBI, further contracting microcirculation blood vessels through pericyte contraction, eventual brain swelling. • The cause of pericyte contraction may be hematoma, high cranial pressure, hypoxia and other factors that lead to the change of cell activity in the neurovascular unit. The mechanism of traumatic brain swelling has not been fully studied, and various existing theories lack strong experimental evidence. Through comprehensive analysis of current theories, it was found that microcirculation disturbance may be an important mechanism in the early stage of traumatic brain swelling. Therefore, we hypothesized that in patients with severe brain injury, partial cerebral venous return decreases, and the cerebral blood flow rate decreases. Due to hematoma, high cranial pressure, hypoxia and other factors, the cells in the neurovascular unit express certain factors, further contracting microcirculation blood vessels through pericyte contraction and obstructing blood flow, resulting in unbalanced cerebral circulation intake and outflow. Excessive vascular congestion occurs in brain tissue, which in turn increases cerebral edema and eventual brain swelling. The purpose of this hypothesis is to supplement the shortcomings of current theories and provide new directions and suggestions for future research on traumatic brain swelling. [ABSTRACT FROM AUTHOR]

No specific or adjunctive therapies exist to treat cerebral malaria (CM) as of date. CM is a neuropathological manifestation of the malaria infection in humans, caused by the hemoparasitic pathogen Plasmodium falciparum. Driven through a multitude of virulence factors, varied immune responses, variations in brain swelling with regard to the age of patients, parasite biomass, and parasite-typing, the essential pathogenetic mechanisms underlying clinical CM have remained elusive. However, a recent series of studies based on molecular, immunologic, and advanced neuroradiologic and machine-learning approaches have unraveled new trends and insights to better understand and focus on the key determinants of CM in humans. This could possibly be the beginning of the design of new and effective adjunctive therapies that may not be common or applicable to the entire malarious world, but that could, rather, be specific to the variations in the determinants of CM.

Background: In cerebral malaria, the retina can be used to understand disease pathogenesis. The mechanisms linking sequestration, brain swelling, and death remain poorly understood. We hypothesized that retinal vascular leakage would be associated with brain swelling.Methods: We used retinal angiography to study blood-retinal barrier integrity. We analyzed retinal leakage, histopathology, brain magnatic resonance imaging (MRI), and associations with death and neurological disability in prospective cohorts of Malawian children with cerebral malaria.Results: Three types of retinal leakage were seen: large focal leak (LFL), punctate leak (PL), and vessel leak. The LFL and PL were associated with death (odds ratio [OR] = 13.20, 95% confidence interval [CI] = 5.21-33.78 and OR = 8.58, 95% CI = 2.56-29.08, respectively) and brain swelling (P < .05). Vessel leak and macular nonperfusion were associated with neurological disability (OR = 3.71, 95% CI = 1.26-11.02 and OR = 9.06, 95% CI = 1.79-45.90). Large focal leak was observed as an evolving retinal hemorrhage. A core of fibrinogen and monocytes was found in 39 (93%) white-centered hemorrhages.Conclusions: Blood-retina barrier breakdown occurs in 3 patterns in cerebral malaria. Associations between LFL, brain swelling, and death suggest that the rapid accumulation of cerebral hemorrhages, with accompanying fluid egress, may cause fatal brain swelling. Vessel leak, from barrier dysfunction, and nonperfusion were not associated with severe brain swelling but with neurological deficits, suggesting hypoxic injury in survivors. [ABSTRACT FROM AUTHOR]

A retrospective study was performed evaluating the volume and T2/T1 signal intensity of orbital fat in five children diagnosed with severe global brain swelling and confirmed cessation of cerebral perfusion. Imaging showed a volume increase (five of five) and a heterogeneous T2-hypointensity of orbital fat (four of five). This preliminary study suggests that swelling and T2-hypointensity of orbital fat may be a marker of global brain swelling and/or increased intracranial pressure. [ABSTRACT FROM AUTHOR]

Background: Peritumoral brain edema is an uncommon but life-threatening side effect of brain tumors radiosurgery. Medical therapy usually alleviates symptoms until edema spontaneously disappears. However, when peritumoral brain edema endangers the patient's life or medical therapy fails to guarantee an acceptable quality of life, surgery might be considered. Case Description: Our report focuses on three patients who developed extensive peritumoral brain edema after radiosurgery. Two were affected by vestibular schwannomas and one by a skull-base meningioma. Peritumoral brain edema worsened despite maximal medical therapy in all cases; therefore, surgical removal of the radiated lesion was carried out. In the first patient, surgery was overdue and resulted in a fatal outcome. On the other hand, in the latter two cases surgery was quickly effective. In all three cases, an unmanageable brain swelling was not found at surgery. Conclusion: Surgical removal of brain tumors previously treated with radiosurgery was safe and effective in resolving shortly peritumoral brain edema. This solution should be considered in patients who do not respond to medical therapy and before worsening of clinical conditions. Interestingly, the expected brain swelling was not confirmed intraoperatively. In our experience, this magnetic resonance finding should not be considered a criterion to delay surgery. [ABSTRACT FROM AUTHOR]

Context: The hydroalcoholic extract of Dorema aucheri Bilhar (Umbelliferae) (DA) leaves, a medicinal plant, has powerful antioxidant properties. Objective: This study evaluates the neuroprotective effects of pre-treatment with DA leaves extract against cerebral ischaemia-induced brain injury through alteration of the antioxidant capacity. Materials and methods: The study was conducted in three groups of Wistar rats (N = 47) as follows; sham, control ischaemic and pre-treated ischaemic groups. Rats were administered a fresh hydroalcoholic extract of DA leaves at a dosage of 200 mg/kg/day for 14 days. Then, the middle cerebral artery (MCA) of the right hemisphere was occluded for 90 min to achieve cerebral ischaemia. After 24 h reperfusion, cerebral infarction and superoxide dismutase (SOD) and catalase activities, as well as malondialdehyde (MDA), glutathione, and NOx contents were determined in the right hemispheres. Results: Occlusion of the right MCA caused noticeable cerebral infarction (298 ± 21 mm3) in control ischaemic group, but pre-treatment with DA extract considerably attenuated it (92 ± 14 mm3) in the pre-treated ischaemic group. DA extract significantly decreased the levels of MDA by 28% and NOx by 11% in pre-treated ischaemic group compared to the control ischaemic group. DA extract also enhanced glutathione content by 7%, SOD activity by 16% and catalase activity by 46% in pre-treated ischaemic rats compared to control ischaemic rats. Discussion and conclusions: DA is able to improve the antioxidant capacity and injuries of ischaemic brain. It is proposed as a neuroprotectant following cerebral ischaemia to decrease the injuries of ischaemic stroke.

Introduction: Pitavastatin, in addition to blood cholesterol-lowering property, has the anti-inflammatory, angiogenic, antioxidant, anti-apoptotic, and antiplatelet effects, which can have neuroprotective effects in treatment of ischemic stroke. Therefore, the present study investigated the protective effects of pitavastatin against the reperfusion injuries and edema in the animal model of local and transient brain ischemia. Methods and Materials: Twenty-one rats were assigned into three groups; sham, control ischemic and treated ischemic groups. Brain ischemia/reperfusion was induced by 90 min middle cerebral artery occlusion (MCAO), followed by 24hours reperfusion. Rats received 4mg/kg pitavastatin intraperitoneally, immediately after termination of MCAO. Neurological deficit score (NDS), infarct volume and brain swelling, as an index of edema, were assessed 24 hours after termination of MCAO. Moreover, oxidative stress markers were determined after termination of reperfusion. Results: MCAO induced neurological dysfunction (3.28±0.28) and brain infarction in control ischemic group (299±21 mm3) in accompany with brain swelling (11.83±2.61 %). Administration of pitavastatin in the treated ischemic rats significantly reduced neurological dysfunction (1.57±0.20), brain infarction (117±28 mm3) and brain swelling (4.75±0.80 %). Also, pitavastatin considerably decreased the mortality of rats in treated ischemic group. Pitavastatin also decreased oxidative damages of ischemic brain and potentiated the brain antioxidant system of ischemic brain through increasing the antioxidant enzymes activity. Conclusion: The findings of present study indicated that pitavastatin, as a potent neuroprotective agent, effectively reduce the reperfusion-induced brain injuries and brain edema, independently of cholesterol lowering effects in the experimental model of ischemic stroke. [ABSTRACT FROM AUTHOR]

Abstract Background Cerebral malaria (CM) is often fatal, and severe brain swelling is a predictor of CM-related mortality. CM is characterized by elevated circulating pro-inflammatory cytokines TNF and IFN-γ and anti-inflammatory cytokine IL-10, however whether cytokine levels correlate with brain swelling severity is unknown. This study therefore was conducted to investigate the relationship between cytokine levels and brain swelling severity in children presenting with CM. Methods A total of 195 Malawian children presenting with CM were recruited and had the concentrations of plasma cytokines determined and compared to brain swelling severity, determined by MRI examination, and graded as severe, moderate, mild or none. Results Levels of IL-1β, IL-6, IL-8 and IL-10 did not differ between CM patients with and without severe brain swelling. Compared to children without brain swelling, IL-12 levels were higher in children with severe swelling (p

Zachary A King,1 Kevin N Sheth,1 W Taylor Kimberly,2 J Marc Simard3 1Department of Neurology, Division of Neurocritical Care and Emergency Neurology, Yale University School of Medicine, New Haven, CT, USA; 2Department of Neurology, Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital, Boston, MA, USA; 3Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, MD, USA Abstract: Glyburide (also known as glibenclamide) is a second-generation sulfonylurea drug that inhibits sulfonylurea receptor 1 (Sur1) at nanomolar concentrations. Long used to target KATP (Sur1–Kir6.2) channels for the treatment of diabetes mellitus type 2, glyburide was recently repurposed to target Sur1–transient receptor potential melastatin 4 (Trpm4) channels in acute central nervous system injury. Discovered nearly two decades ago, SUR1–TRPM4 has emerged as a critical target in stroke, specifically in large hemispheric infarction, which is characterized by edema formation and life-threatening brain swelling. Following ischemia, SUR1–TRPM4 channels are transcriptionally upregulated in all cells of the neurovascular unit, including neurons, astrocytes, microglia, oligodendrocytes and microvascular endothelial cells. Work by several independent laboratories has linked SUR1–TRPM4 to edema formation, with blockade by glyburide reducing brain swelling and death in preclinical models. Recent work showed that, following ischemia, SUR1–TRPM4 co-assembles with aquaporin-4 to mediate cellular swelling of astrocytes, which contributes to brain swelling. Additionally, recent work linked SUR1–TRPM4 to secretion of matrix metalloproteinase-9 (MMP-9) induced by recombinant tissue plasminogen activator in activated brain endothelial cells, with blockade of SUR1–TRPM4 by glyburide reducing MMP-9 and hemorrhagic transformation in preclinical models with recombinant tissue plasminogen activator. The recently completed GAMES (Glyburide Advantage in Malignant Edema and Stroke) clinical trials on patients with large hemispheric infarctions treated with intravenous glyburide (RP-1127) revealed promising findings with regard to brain swelling (midline shift), MMP-9, functional outcomes and mortality. Here, we review key elements of the basic science, preclinical experiments and clinical studies, both retrospective and prospective, on glyburide in focal cerebral ischemia and stroke. Keywords: glyburide, sulfonylurea receptor 1, stroke, cerebral ischemia, brain swelling, malignant edema, matrix metalloproteinase-9

Severe brain swelling during routine neurosurgery can herald serious consequences. Failure to control brain swelling despite adequate measures warns of a surgical cause and should be dealt efficiently. We report a case of an adult female who developed intraoperative acute subdural haematoma (SDH) and consequent intractable brain swelling during surgery of supratentorial arteriovenous malformation (AVM). Such a manifestation of contralateral acute SDH during supratentorial AVM surgery has not been reported earlier.

The lack of inclusion of comorbidities in animal models of stroke may underlie the limited development of therapy in stroke. Previous studies in mice deficient of CD36, an immune receptor, indicated its contribution to stroke-induced inflammation and injury in hyperlipidemic conditions. The current study, therefore, tested whether pharmacological inhibition of CD36 provides neuroprotection in hyperlipidemic stroke. The hyperlipidemic mice subjected to stroke showed an exacerbation of infarct size and profound brain swelling. However, post-stroke treatment with CD36 inhibitors did not reduce, and in some cases worsened, acute stroke outcome, suggesting potential benefits of elevated CD36 in the post-stroke brain in a hyperlipidemic condition. On the other hand, chronic treatment of a CD36 inhibitor prior to stroke significantly reduced stroke-induced brain swelling. There was a trend toward infarct reduction, although it did not reach statistical significance. The observed benefit of preventative CD36 inhibition is in line with previously reported smaller infarct volume and swelling in CD36 KO mice. Thus, the current findings suggest that insights gained from the genetic models should be carefully considered before the implementation of pharmacological interventions, as a potential therapeutic strategy may depend on preventative treatment or a post-stroke acute treatment paradigm. [ABSTRACT FROM AUTHOR]

Red blood cell (RBC) lysis within the hematoma causes brain injury following intracerebral hemorrhage. Peroxiredoxin 2 (PRX-2) is the third most abundant protein in RBCs and this study examined the potential role of PRX-2 in inducing brain injury in rats. First, adult male Sprague-Dawley rats had an intracaudate injection of lysed RBCs or saline. Brains were harvested at 1 h to measure PRX-2 levels. Second, rats had an intracaudate injection of either recombinant PRX-2, heat-inactivated PRX-2, or saline. Third, rats had intracaudate co-injection of lysed RBCs with conoidin A, a PRX-2 inhibitor, or vehicle. For the second and third parts of studies, behavioral tests were performed and all rats had magnetic resonance imaging prior to euthanasia for brain immunohistochemistry and Western blotting. We found that brain PRX-2 levels were increased after lysed RBC injection. Intracaudate injection of PRX-2 resulted in blood-brain barrier disruption, brain swelling, neutrophil infiltration, microglia activation, neuronal death, and neurological deficits. Intracerebral injection of lysed RBCs induced brain injury, which was reduced by conoidin A. These results suggest that extracellular PRX-2 released from hematoma can cause brain injury following brain hemorrhage and could be a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Some previously reported cases of brain evisceration in catastrophic craniocerebral injuries showed the presence of brain swelling. The aim of this study was to observe the occurrence of focal or diffuse brain swelling in such cases in order to explain the underlying mechanism. An observational autopsy study included 23 adults, 18 males and 5 females, whose average age was 48 ± 22 years (range: 19–89 years) and who died as the result of catastrophic craniocerebral injury with brain evisceration. In all the examined cases, either focal (12 cases) or diffuse (11 cases) brain swelling was present. Grossly visible brain contusions (either cortical or deep) were rarely present – only in 6 out of 23 cases, while microscopic brain contusions were observed in 22 out of 23 cases, with 1 remaining case of microscopic subarachnoid bleeding. Blood aspiration in the lungs, as a vital reaction, was noted in 20 out of 23 cases. Microscopic examination showed absence of edema in 20 cases and mild edema in only 3 cases, while microscopic signs of moderate or severe edema were absent. Brain swelling in cases of brain evisceration likely represents a biomechanical reaction (i.e. decompression) due to a sudden decrease in intracranial pressure. The rapidity of death, together with marked absence of microscopic signs of edema, suggests that this is not a form of biological response to injury, but rather a pure physical phenomenon, strictly in a living person. In such cases, the occurrence of brain swelling and parenchymal microbleeding should be considered vital reactions. [ABSTRACT FROM AUTHOR]

Context: The hydroalcoholic extract of Dorema aucheri Bilhar (Umbelliferae) (DA) leaves, a medicinal plant, has powerful antioxidant properties. Objective: This study evaluates the neuroprotective effects of pre-treatment with DA leaves extract against cerebral ischaemia-induced brain injury through alteration of the antioxidant capacity. Materials and methods: The study was conducted in three groups of Wistar rats (N = 47) as follows; sham, control ischaemic and pre-treated ischaemic groups. Rats were administered a fresh hydroalcoholic extract of DA leaves at a dosage of 200 mg/kg/day for 14 days. Then, the middle cerebral artery (MCA) of the right hemisphere was occluded for 90 min to achieve cerebral ischaemia. After 24 h reperfusion, cerebral infarction and superoxide dismutase (SOD) and catalase activities, as well as malondialdehyde (MDA), glutathione, and NOx contents were determined in the right hemispheres. Results: Occlusion of the right MCA caused noticeable cerebral infarction (298 ± 21 mm3) in control ischaemic group, but pre-treatment with DA extract considerably attenuated it (92 ± 14 mm3) in the pre-treated ischaemic group. DA extract significantly decreased the levels of MDA by 28% and NOx by 11% in pre-treated ischaemic group compared to the control ischaemic group. DA extract also enhanced glutathione content by 7%, SOD activity by 16% and catalase activity by 46% in pre-treated ischaemic rats compared to control ischaemic rats. Discussion and conclusions: DA is able to improve the antioxidant capacity and injuries of ischaemic brain. It is proposed as a neuroprotectant following cerebral ischaemia to decrease the injuries of ischaemic stroke. [ABSTRACT FROM AUTHOR]

This meta-analysis aimed to compare the risk of brain swelling during craniotomy between propofol-based and volatile-based anesthesia. Meta-analysis of randomized controlled trials (RCTs). Operating room. Propofol-based anesthesia. Adult patients undergoing craniotomy. Databases, including EMBASE, MEDLINE, Google Scholar, and Cochrane Library, were searched from inception to April 2023. The primary outcome was the risk of brain swelling, while the secondary outcomes included the impact of anesthetic regimens on surgical and recovery outcomes, as well as the risk of hemodynamic instability. Our meta-analysis of 17 RCTs showed a significantly lower risk of brain swelling (risk ratio [RR]: 0.85, p = 0.03, I2 = 21%, n = 1976) in patients receiving propofol than in those using volatile agents, without significant differences in surgical time or blood loss between the two groups. Moreover, propofol was associated with a lower intracranial pressure (ICP) (mean difference: −4.06 mmHg, p < 0.00001, I2 = 44%, n = 409) as well as a lower risk of tachycardia (RR = 0.54, p = 0.005, I2 = 0%, n = 822) and postoperative nausea/vomiting (PONV) (RR = 0.59, p = 0.002, I2 = 19%, n = 1382). There were no significant differences in other recovery outcomes (e.g., extubation time), risk of bradycardia, hypertension, or hypotension between the two groups. Subgroup analysis indicated that propofol was not associated with a reduced risk of brain swelling when compared to individual volatile agents. Stratified by craniotomy indications, propofol reduced brain swelling in elective craniotomy, but not in emergency craniotomy (e.g., traumatic brain injury), when compared to volatile anesthetics. By reviewing the available evidence, our results demonstrate the beneficial effects of propofol on the risk of brain swelling, ICP, PONV, and intraoperative tachycardia. In emergency craniotomy for traumatic brain injury and subarachnoid hemorrhage, brain swelling showed no significant difference between propofol and volatile agents. Further large-scale studies are warranted for verification. • Analysis showed a lower brain swelling (BS) risk with propofol than volatile agents. • Propofol correlated with a lower intracranial pressure and risk of nausea/vomiting. • Propofol was also linked to a lower risk of intraoperative tachycardia. • Propofol lowered BS in elective craniotomy versus volatile anesthetics. • Propofol didn't reduce BS in emergency craniotomy vs. volatile anesthetics. [ABSTRACT FROM AUTHOR]

Increased intracranial pressure (ICP) is frequently encountered in the neurosurgical setting. A multitude of tactics exists to reduce ICP, ranging from patient position and medications to cerebrospinal fluid diversion and surgical decompression. A vast amount of literature has been published regarding ICP management in the critical care setting, but studies specifically tailored toward the management of intraoperative acute increases in ICP or brain bulk are lacking. Compartmentalizing the intracranial space into blood, brain tissue, and cerebrospinal fluid and understanding the numerous techniques available to affect these individual compartments can guide the surgical team to quickly identify increased brain bulk and respond appropriately. Rapidly instituting measures for brain relaxation in the operating room is essential in optimizing patient outcomes. Knowledge of the efficacy, rapidity, feasibility, and risks of the various available interventions can aid the team to properly tailor their approach to each individual patient. In this article, we present the first evidence-based review of intraoperative management of ICP and brain bulk. [ABSTRACT FROM AUTHOR]

In severe traumatic brain injury (TBI), contusions often are worsened by contusion expansion or hemorrhagic progression of contusion (HPC), which may double the original contusion volume and worsen outcome. In humans and rodents with contusion-TBI, sulfonylurea receptor 1 (SUR1) is upregulated in microvessels and astrocytes, and in rodent models, blockade of SUR1 with glibenclamide reduces HPC. SUR1 does not function by itself, but must co-assemble with either KIR6.2 or transient receptor potential cation channel subfamily M member 4 (TRPM4) to form KATP (SUR1-KIR6.2) or SUR1-TRPM4 channels, with the two having opposite effects on membrane potential. Both KIR6.2 and TRPM4 are reportedly upregulated in TBI, especially in astrocytes, but the identity and function of SUR1-regulated channels post-TBI is unknown. Here, we analyzed human and rat brain tissues after contusion-TBI to characterize SUR1, TRPM4, and KIR6.2 expression, and in the rat model, to examine the effects on HPC of inhibiting expression of the three subunits using intravenous antisense oligodeoxynucleotides (AS-ODN). Glial fibrillary acidic protein (GFAP) immunoreactivity was used to operationally define core versus penumbral tissues. In humans and rats, GFAP-negative core tissues contained microvessels that expressed SUR1 and TRPM4, whereas GFAP-positive penumbral tissues contained astrocytes that expressed all three subunits. Förster resonance energy transfer imaging demonstrated SUR1-TRPM4 heteromers in endothelium, and SUR1-TRPM4 and SUR1-KIR6.2 heteromers in astrocytes. In rats, glibenclamide as well as AS-ODN targeting SUR1 and TRPM4, but not KIR6.2, reduced HPC at 24 h post-TBI. Our findings demonstrate upregulation of SUR1-TRPM4 and KATP after contusion-TBI, identify SUR1-TRPM4 as the primary molecular mechanism that accounts for HPC, and indicate that SUR1-TRPM4 is a crucial target of glibenclamide. [ABSTRACT FROM AUTHOR]

Severe brain swelling during routine neurosurgery can herald serious consequences. Failure to control brain swelling despite adequate measures warns of a surgical cause and should be dealt efficiently. We report a case of an adult female who developed intraoperative acute subdural haematoma (SDH) and consequent intractable brain swelling during surgery of supratentorial arteriovenous malformation (AVM). Such a manifestation of contralateral acute SDH during supratentorial AVM surgery has not been reported earlier. [ABSTRACT FROM AUTHOR]

Pseudohypoxic brain swelling (PHBS) is known to be an uncommon event that may occur during and following an uneventful brain surgery, when negative suction drainage is used. The cerebrospinal fluid loss related to suction drainage can evoke intracranial hypotension that progress to PHBS. The main presentations of PHBS are sudden unexpected circulatory collapses, such as severe bradycardia, hypotension, cardiac arrest, consciousness deterioration and diffuse brain swelling as seen with brain computerized tomography (CT). We present a stuporous 22-year-old patient who underwent cranioplasty under general anesthesia. The entire course of the general anesthesia and operation progressed favorably. However, the time of scalp suture completion, sudden bradycardia and hypotension occurred, followed by cardiac arrest immediately after initiation of subgaleal and epidural suction drainage. After successful resuscitation, the comatose patient was transferred to the neurosurgical intensive care unit and PHBS was confirmed using brain CT.

Background: Spontaneous intracerebral hemorrhage (ICH) leaves most survivors dependent at follow-up. The importance of promoting M2-like microglial responses is increasingly recognized as a key element to ameliorate brain injury following ICH. The osmotherapeutic agents, mannitol and hypertonic saline (HTS), which are routinely used to reduce intracranial pressure, have been shown to reduce neuroinflammation in experimental ischemic and traumatic brain injury, but anti-inflammatory effects of osmotherapies have not been investigated in ICH.Methods: We studied the effects of iso-osmotic mannitol and HTS in rat models of ICH utilizing high-dose and moderate-dose collagenase injections into the basal ganglia, associated with high and low mortality, respectively. We studied the effects of osmotherapies, first given 5 h after ICH induction, and then administered every 12 h thereafter (4 doses total). Immunohistochemistry was used to quantify microglial activation and polarization.Results: Compared to controls, mannitol and HTS increased plasma osmolarity 1 h after infusion (301 ± 1.5, 315 ± 4.2 and 310 ± 2.0 mOsm/kg, respectively), reduced mortality at 48 h (82, 36 and 53%, respectively), and reduced hemispheric swelling at 48 h (32, 21, and 17%, respectively). In both perihematomal and contralateral tissues, mannitol and HTS reduced activation of microglia/macrophages (abundance and morphology of Iba1 + cells), and in perihematomal tissues, they reduced markers of the microglia/macrophage M1-like phenotype (nuclear p65, TNF, and NOS2), increased markers of the microglia/macrophage M2-like phenotype (arginase, YM1, and pSTAT3), and reduced infiltration of CD45 + cells.Conclusions: Repeated dosing of osmotherapeutics at regular intervals may be a useful adjunct to reduce neuroinflammation following ICH. [ABSTRACT FROM AUTHOR]