Infectious Diseases Society of America.

Purpose—The aim of this guideline is to present current and comprehensive recommendations for the diagnosis and treatment of aneurysmal subarachnoid hemorrhage (aSAH). Methods—A formal literature s...

Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

Blood vessels are critical to deliver oxygen and nutrients to all of the tissues and organs throughout the body. The blood vessels that vascularize the central nervous system (CNS) possess unique properties, termed the blood-brain barrier, which allow these vessels to tightly regulate the movement of ions, molecules, and cells between the blood and the brain. This precise control of CNS homeostasis allows for proper neuronal function and also protects the neural tissue from toxins and pathogens, and alterations of these barrier properties are an important component of pathology and progression of different neurological diseases. The physiological barrier is coordinated by a series of physical, transport, and metabolic properties possessed by the endothelial cells (ECs) that form the walls of the blood vessels, and these properties are regulated by interactions with different vascular, immune, and neural cells. Understanding how these different cell populations interact to regulate the barrier properties is essential for understanding how the brain functions during health and disease.

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The Blood–Brain Barrier

Disorders characterized by ischemia/reperfusion (I/R), such as myocardial infarction, stroke, and peripheral vascular disease, continue to be among the most frequent causes of debilitating disease and death. Tissue injury and/or death occur as a result of the initial ischemic insult, which is determined primarily by the magnitude and duration of the interruption in the blood supply, and then subsequent damage induced by reperfusion. During prolonged ischemia, ATP levels and intracellular pH decrease as a result of anaerobic metabolism and lactate accumulation. As a consequence, ATPase-dependent ion transport mechanisms become dysfunctional, contributing to increased intracellular and mitochondrial calcium levels (calcium overload), cell swelling and rupture, and cell death by necrotic, necroptotic, apoptotic, and autophagic mechanisms. Although oxygen levels are restored upon reperfusion, a surge in the generation of reactive oxygen species occurs and proinflammatory neutrophils infiltrate ischemic tissues to exacerbate ischemic injury. The pathologic events induced by I/R orchestrate the opening of the mitochondrial permeability transition pore, which appears to represent a common end-effector of the pathologic events initiated by I/R. The aim of this treatise is to provide a comprehensive review of the mechanisms underlying the development of I/R injury, from which it should be apparent that a combination of molecular and cellular approaches targeting multiple pathologic processes to limit the extent of I/R injury must be adopted to enhance resistance to cell death and increase regenerative capacity in order to effect long-lasting repair of ischemic tissues.

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Cell Biology of Ischemia/Reperfusion Injury

Inflammation plays an important role in the pathogenesis of ischemic stroke and other forms of ischemic brain injury. Experimentally and clinically, the brain responds to ischemic injury with an acute and prolonged inflammatory process, characterized by rapid activation of resident cells (mainly microglia), production of proinflammatory mediators, and infiltration of various types of inflammatory cells (including neutrophils, different subtypes of T cells, monocyte/macrophages, and other cells) into the ischemic brain tissue. These cellular events collaboratively contribute to ischemic brain injury. Despite intense investigation, there are still numerous controversies concerning the time course of the recruitment of inflammatory cells in the brain and their pathogenic roles in ischemic brain injury. In this review, we provide an overview of the time-dependent recruitment of different inflammatory cells following focal cerebral I/R. We discuss how these cells contribute to ischemic brain injury and highlight certain recent findings and currently unanswered questions about inflammatory cells in the pathophysiology of ischemic stroke.

https://jlb.onlinelibrary.wiley.com/doi/epdf/10.1189/jlb.1109766

Inflammatory mechanisms in ischemic stroke: role of inflammatory cells.

Inflammation plays an important role in the pathogenesis of ischemic stroke and other forms of ischemic brain injury. Increasing evidence suggests that inflammatory response is a double-edged sword, as it not only exacerbates secondary brain injury in the acute stage of stroke but also beneficially contributes to brain recovery after stroke. In this article, we provide an overview on the role of inflammation and its mediators in acute ischemic stroke. We discuss various pro-inflammatory and anti-inflammatory responses in different phases after ischemic stroke and the possible reasons for their failures in clinical trials. Undoubtedly, there is still much to be done in order to translate promising pre-clinical findings into clinical practice. A better understanding of the dynamic balance between pro- and anti-inflammatory responses and identifying the discrepancies between pre-clinical studies and clinical trials may serve as a basis for designing effective therapies.

/pdf/role-of-inflammation-and-its-mediators-in-acute-ischemic-2wdpto1g7g.pdf

Role of Inflammation and Its Mediators in Acute Ischemic Stroke

Objective To characterize admissions related to ventricular shunts in the year 2000 in terms of diagnoses, procedures, socioeconomic status, and other related data. Methods The Nationwide Inpatient Sample database (year 2000) was analyzed retrospectively. We reviewed 7.45 million patient admissions for primary International Classification of Diseases, 9th Revision, procedure codes 023 to 0243 (ventricular shunts to peritoneal, atrial, pleural, and urinary systems for initial placement, revision, and removal); admissions listing ventriculostomy placement (code 022) were excluded from analysis. Results Five thousand five hundred seventy-four admissions were identified. Admission sources primarily were routine (58.8%) and the emergency department (32.4%). Admission types primarily were elective (43.3%), emergent (33.2%), and urgent (21.9%). The top three primary diagnoses treated were shunt malfunction (40.7%), noncommunicating hydrocephalus (16.6%), and communicating hydrocephalus (13.2%). Shunt infection was the primary diagnosis in 7.2% of admissions. Age frequency of admissions was nonparametric, being highest for infants; the average stay was 8.4 +/- 0.2 days (standard error range, 0-243 d). The most common procedures were ventriculoperitoneal shunt placement (43.4%) and ventricular shunt replacement (42.8%); ventricular shunt removal occurred in 7.3% of admissions, whereas ventricle-to-thorax (0.6%), ventricle-to-circulatory system (0.5%), and ventricle-to-urinary system (0.05%) shunts were rare. Average cost was $35,816 +/- $810 (standard error range, $137-$814,748). Primary payers primarily were private insurers (43.8%), Medicare (26.0%), and Medicaid (24.5%). Disposition mainly was routine (78.4%, with home health care in 6.5%), and inpatient mortality was 2.7%. There was no socioeconomic disproportion in treatment with respect to average household income. Conclusion Ventricular shunts as primary procedures constitute a significant medical and economic problem.

Implanted ventricular shunts in the United States: the billion-dollar-a-year cost of hydrocephalus treatment.

Few studies have examined the signaling pathways that contribute to early brain injury after subarachnoid hemorrhage (SAH). Using a rat SAH model, the authors explored the role of vascular endothelial growth factor (VEGF) and mitogen-activation protein kinase (MAPK) in early brain injury. Male Sprague-Dawley rats (n = 172) weighing 300 to 350 g were used for the experimental SAH model, which was induced by puncturing the bifurcation of the left anterior cerebral and middle cerebral arteries. The blood-brain barrier (BBB), brain edema, intracranial pressure, and mortality were evaluated at 24 hours after SAH. The phosphorylation of VEGF and different MAPK subgroups (ERK1/2, p38, and JNK) were examined in both the cortex and the major cerebral arteries. Experimental SAH increased intracranial pressure, BBB permeability, and brain edema and produced high mortality. SAH induced phosphorylation of VEGF and MAPKs in the cerebral arteries and, to a lesser degree, in the cortex. PP1, an Src-family kinase inhibitor, reduced BBB permeability, brain edema, and mortality and decreased the phosphorylation of VEGF and MAPKs. The authors conclude that VEGF contributes to early brain injury after SAH by enhancing the activation of the MAPK pathways, and that the inhibition of these pathways might offer new treatment strategies for SAH.

Signaling pathways for early brain injury after subarachnoid hemorrhage.

The extended frontal approach is a modification of the transbasal approach of Derome. The addition of a bilateral orbitofrontal or orbitofrontoethmoidal osteotomy improves the exposure of midline lesions of the anterior, middle, and posterior skull base, while minimizing the need for frontal lobe retraction. The authors present a 5-year experience with 49 patients operated on via the extended frontal approach. In seven patients, the extended frontal approach was used alone; in the remaining 42, it was combined with other skull base approaches. Highly malignant tumors were removed en bloc, whereas benign tumors and low-grade malignancies were removed either en bloc or piecemeal. Reconstruction was usually performed using fascia lata, a pericranial flap, and/or autologous fat. A temporalis muscle flap or a distant microvascular free flap was required for some patients. One patient died 1 month postoperatively due to superior mesenteric artery thrombosis. Three patients had postoperative infections, two had cerebrospinal fluid leaks requiring reoperation, and four had brain contusions or hematomas. All but two patients recovered to their preoperative functional level. After an average follow-up period of 26 months (range 6 to 56 months), 64% of patients with benign lesions, 64% of patients with low-grade malignancies, and 44% of patients with high-grade lesions were alive with no evidence of disease.

Anil Nanda

Papers

Role of Inflammation and Its Mediators in Acute Ischemic Stroke

Implanted ventricular shunts in the United States: the billion-dollar-a-year cost of hydrocephalus treatment.

Signaling pathways for early brain injury after subarachnoid hemorrhage.

The extended frontal approach to tumors of the anterior, middle, and posterior skull base

Spontaneous bowel perforation after ventriculoperitoneal shunt surgery: case report and a review of 45 cases