Background And Aims: After peripheral nerve stretch injury, most degenerating axons are thought to become disconnected at the time of injury, referred to as primary axotomy. The possibility of secondary axotomy-a delayed and potentially reversible form of disconnection-has not been evaluated. Here, we investigated secondary axotomy in a rat model of sciatic nerve stretch injury.
View Article and Find Full Text PDFIn 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.
View Article and Find Full Text PDFIn previous studies, the incidence of traumatic intracranial aneurysms (TICAs) after civilian gunshot wound to the head (cGSWH) was ∼3%. Given the use of delayed vessel imaging, we hypothesize that a significant fraction of TICAs is missed on initial non-contrasted scans. This study was designed to characterize acute TICAs using admission computed tomographic angiography (aCTA) in cGSWH.
View Article and Find Full Text PDFObjective: External ventricular drain (EVD) placement is a common neurosurgical procedure that can be performed at bedside. A frequent complication following EVD placement is catheter-associated hemorrhage (CAH). The hemorrhage itself is rarely clinically significant but may be complicated in patients taking anticoagulant or antiplatelet (AC/AP) medications.
View Article and Find Full Text PDFBackground: Nerve transfer surgery is sometimes offered to patients with acute flaccid myelitis (AFM). The objectives of this study were to evaluate surgical efficacy, assess which clinical and neurophysiological data are valuable for preoperative planning, and report long-term outcomes.
Methods: This is a single-center, retrospective case series of patients with AFM who received nerve transfer surgery.
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).
View Article and Find Full Text PDFBrain swelling causes morbidity and mortality in various brain injuries and diseases but lacks effective treatments. Brain swelling is linked to the influx of water into perivascular astrocytes through channels called aquaporins. Water accumulation in astrocytes increases their volume, which contributes to brain swelling.
View Article and Find Full Text PDFBackground: Spontaneous intracerebral hemorrhage (sICH) is a major health concern and has high mortality rates up to 52%. Despite a decrease in its incidence, fatality rates remain unchanged; understanding and preventing of factors associated with mortality and treatments for these are needed. Blood pressure variability (BPV) has been shown to be a potential modifiable factor associated with clinical outcomes in patients with traumatic intracerebral hemorrhage and sICH.
View Article and Find Full Text PDFBackground: Decompression of the injured spinal cord confers neuroprotection. Compared with timing of surgery, verification of surgical decompression is understudied.
Objective: To compare the judgment of cervical spinal cord decompression using real-time intraoperative ultrasound (IOUS) following laminectomy with postoperative MRI and CT myelography.
Expansion duraplasty to reopen effaced subarachnoid space and improve spinal cord perfusion, autoregulation, and spinal pressure reactivity index (sPRX) has been advocated in patients with traumatic cervical spinal cord injury (tCSCI). We designed this study to identify candidates for expansion duraplasty, based on the absence of cerebrospinal fluid (CSF) interface around the spinal cord on magnetic resonance imaging (MRI), in the setting of otherwise adequate bony decompression. Over a 61-month period, 104 consecutive American Spinal Injury Association Impairment Scale (AIS) grades A-C patients with tCSCI had post-operative MRI to assess the adequacy of surgical decompression.
View Article and Find Full Text PDFBackground: Consensus is currently lacking in the optimal treatment for blunt traumatic cerebral venous sinus thrombosis (tCVST). Anticoagulation (AC) is used for treating spontaneous CVST, but its role in tCVST remains unclear.
Objective: To investigate the characteristics and outcomes of patients treated with AC compared with patients managed conservatively.
Background: Malignant cerebral edema (MCE) and intracranial hemorrhage (ICH) are associated with poor neurological outcomes despite revascularization after mechanical thrombectomy (MT). The factors associated with the development of MCE and ICH after MT are not well understood.
Objective: To determine periprocedural factors associated with MCE, ICH, and poor functional outcome.
Hemorrhage in the central nervous system (CNS), including intracerebral hemorrhage (ICH), intraventricular hemorrhage (IVH), and aneurysmal subarachnoid hemorrhage (aSAH), remains highly morbid. Trials of medical management for these conditions over recent decades have been largely unsuccessful in improving outcome and reducing mortality. Beyond its role in creating mass effect, the presence of extravasated blood in patients with CNS hemorrhage is generally overlooked.
View Article and Find Full Text PDFThe perivascular astrocyte endfoot is a specialized and diffusion-limited subcellular compartment that fully ensheathes the cerebral vasculature. Despite their ubiquitous presence, a detailed understanding of endfoot physiology remains elusive, in part due to a limited understanding of the proteins that distinguish the endfoot from the greater astrocyte body. Here, we developed a technique to isolate astrocyte endfeet from brain tissue, which was used to study the endfoot proteome in comparison to the astrocyte somata.
View Article and Find Full Text PDFBackground: Patients who survive aneurysmal subarachnoid hemorrhage (aSAH) are at risk for delayed neurological deficits (DND) and cerebral infarction. In this exploratory cohort comparison analysis, we compared in-hospital outcomes of aSAH patients administered a low-dose intravenous heparin (LDIVH) infusion (12 U/kg/h) vs those administered standard subcutaneous heparin (SQH) prophylaxis for deep vein thrombosis (DVT; 5000 U, 3 × daily).
Objective: To assess the safety and efficacy of LDIVH in aSAH patients.
Background And Purpose: Previous studies in acute ischemic stroke have demonstrated the importance of minimizing delays to endovascular treatment and keeping thrombectomy procedural times at <30-60 minutes. The purpose of this study was to investigate the impact of thrombectomy procedural times on clinical outcomes.
Materials And Methods: We retrospectively compared 319 patients having undergone thrombectomy according to procedural time (<30 minutes, 30-60 minutes, and >60 minutes) and time from stroke onset to endovascular therapy (≤6 or >6 hours).
Annu Rev Pharmacol Toxicol
January 2020
Cerebral edema, a common and often fatal companion to most forms of acute central nervous system disease, has been recognized since the time of ancient Egypt. Unfortunately, our therapeutic armamentarium remains limited, in part due to historic limitations in our understanding of cerebral edema pathophysiology. Recent advancements have led to a number of clinical trials for novel therapeutics that could fundamentally alter the treatment of cerebral edema.
View Article and Find Full Text PDFPrimary blast traumatic brain injury (bTBI) accounts for a significant proportion of wartime trauma. Previous studies have demonstrated direct brain injury by blast waves, but the effect of the location of the blast epicenter on the skull with regard to brain injury remains poorly characterized. In order to investigate the role of the blast epicenter location, we modified a previously established rodent model of cranium-only bTBI to evaluate two specific blast foci: a rostrally focused blast centered on bregma (B-bTBI), which excluded the foramen magnum region, and a caudally focused blast centered on the occipital crest, which included the foramen magnum region (FM-bTBI).
View Article and Find Full Text PDFGlioma is a unique neoplastic disease that develops exclusively in the central nervous system (CNS) and rarely metastasizes to other tissues. This feature strongly implicates the tumor-host CNS microenvironment in gliomagenesis and tumor progression. We investigated the differences and similarities in glioma biology as conveyed by transcriptomic patterns across four mammalian hosts: rats, mice, dogs, and humans.
View Article and Find Full Text PDFIn nutrient restricted environments, the yeast endosulfines Igo1/2 are activated via TORC1 inhibition and function critically to initiate and coordinate the cellular stress response that promotes survival. We examined expression of αEnsa, the mammalian homolog of yeast endosulfines, in rat stroke. Prominent neuronal upregulation of αEnsa was identified in 3 patterns within the ischemic gradient: (1) neurons in GFAP-/HSF1+ cortex showed upregulation and near-complete nuclear translocation of αEnsa protein within hours of ischemic onset; (2) neurons in GFAP+/HSF1+ cortex showed upregulation in cytoplasm and nuclei that persisted for days; (3) neurons in GFAP+/HSF1- cortex showed delayed cytosolic-only upregulation that persisted for days.
View Article and Find Full Text PDFAstrocyte swelling occurs after central nervous system injury and contributes to brain swelling, which can increase mortality. Mechanisms proffered to explain astrocyte swelling emphasize the importance of either aquaporin-4 (AQP4), an astrocyte water channel, or of Na -permeable channels, which mediate cellular osmolyte influx. However, the spatio-temporal functional interactions between AQP4 and Na -permeable channels that drive swelling are poorly understood.
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