Neuronal expression of familial Alzheimer's disease (AD)-mutant human amyloid precursor protein (hAPP) and hAPP-derived amyloid-β (Aβ) peptides causes synaptic dysfunction, inflammation, and abnormal cerebrovascular tone in transgenic mice. Fatty acids may be involved in these processes, but their contribution to AD pathogenesis is uncertain. A lipidomics approach to broadly profile fatty acids in brain tissues of hAPP mice revealed an increase in arachidonic acid and its metabolites, suggesting increased activity of the group IV isoform of phospholipase A2 (GIVA-PLA2). Levels of activated GIVA-PLA2 in the hippocampus were increased in AD patients and hAPP mice. Aβ caused a dose-dependent increase in GIVA-PLA2 phosphorylation in neuronal cultures. Inhibition of GIVA-PLA2 diminished Aβ-induced neurotoxicity. Genetic ablation or reduction of GIVA-PLA2 protected hAPP mice against Aβ-dependent deficits in learning and memory, behavioral alterations, and premature mortality. Inhibition of GIVA-PLA2 may be of benefit in the treatment and prevention of AD.
Tentorial DAVF can be differentiated on the basis of fistula location, dural base, associated sinus, and direction of venous drainage. The operative strategy for each type is almost algorithmic, with each type having an optimum surgical approach and an optimum patient position that allows gravity to retract the brain, open subarachnoid planes, and shorten dissection times. No matter the type, the fistula is treated microsurgically by simple interruption of the draining vein.
Essential fatty acids (EFA) play a critical role in the brain and regulate many of the processes altered in Alzheimer's disease (AD). Technical advances are allowing for the dissection of complex lipid pathways in normal and diseased states. Arachidonic acid (AA) and specific isoforms of phospholipase A 2 (PLA 2 ) appear to play critical mediator roles in amyloid-β (Aβ) -induced pathogenesis, leading to learning, memory, and behavioral impairments in mouse models of AD. These findings and ongoing research into lipid biology in AD and related disorders promise to reveal new pharmacological targets that may lead to better treatments for these devastating conditions.
Use of the Hemedex thermal diffusion probe appears to be a safe and feasible method that enables continuous monitoring of CBF at the bedside. Cerebral autoregulation and CO(2) vasoreactivity can be assessed in patients with severe TBI using the CBF probe by calculating (loc)CVR in response to MAP and hyperventilation challenges. Determining whether CVR increases or decreases with a MAP challenge ((loc)CVR(normalized)) may be a simple provocative test to determine patients' autoregulatory status following severe TBI and helping to optimize CPP management.
This analysis confirms the observation that children fare better than adults after microsurgical AVM resection. This discrepancy cannot be explained by differences in AVM anatomy, lesion rupture rates, presenting neurological condition, or treatment techniques, leading the authors to infer that neural plasticity may augment surgical tolerance and recovery in children. These findings bolster the choice of aggressive microsurgical management of AVMs and recalibration of surgical risk assessment in children.
Distal aneurysms of basilar perforating and circumferential arteries are exceedingly rare. The authors encountered one patient with a distal basilar perforating artery aneurysm and two with aneurysms arising from circumferential branches of the basilar artery (BA). The diagnostic features, microsurgical treatment, and outcomes in these three patients are described. The first patient, a 27-year-old man, presented with an angiogram-negative subarachnoid hemorrhage (SAH), and subsequent readmission for a new hemorrhage revealed a centrally thrombosed aneurysm arising from a basilar apex perforating artery. The second patient, a 68-year-old man, presented for follow-up evaluation 2 months after an angiogram-negative SAH, and an aneurysm was identified on a circumferential artery originating from the BA trunk. The third patient, a 2-year-old boy, presented with blunt head trauma and a pseudoaneurysm arising from a basilar apex circumferential artery. All three aneurysms were managed microsurgically with aneurysm trapping, via either an orbitozygomatic or an extended retrosigmoid approach. Occlusion of the distal perforating or circumferential artery was well tolerated in all cases, with no neurological sequelae resulting from surgery. Features common to all three aneurysms were dolichoectatic morphology, intraluminal thrombus, and SAH. These aneurysms may be difficult to diagnose given their small size and delayed filling on angiographic studies. Consequently, their presence in cases of angiogram-negative SAH may be underestimated. These aneurysms are not amenable to endovascular treatment, but excellent results can be obtained with microsurgical exposure and trapping.
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