Neurosurgery
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Brain mapping has undergone a paradigm shift from functional localization to focusing on complex network connectivity. Central to this has been the search for the connectome or the brain's wiring diagram. Modeling the effects of focal lesions using graph theory allows consideration of how important a region is to network function and the effects of its removal. Our aim is to determine the feasibility of applying connectomics to neurosurgery and determine the key topological characteristics of patients with real lesion. ⋯ Our refined analysis pipeline confirms the feasibility of performing complex network analysis with graph theory in patients with real lesions and is a novel approach to preoperative brain mapping. Potential discrepancies between the effects of real and simulated lesions may allow identification of mechanisms behind network plasticity. Preoperative mapping of network hubs and robustness is a novel approach for understanding the mechanisms of how higher cognitive processes are affected by and recover from real lesions.
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Previous studies have demonstrated a profound dysfunction of cerebral metabolism following traumatic brain injury (TBI). Despite overall depression of cerebral metabolism, the cerebral metabolic rate (CMR) of oxygen is depressed out of proportion to the mildly reduced CMRglucose. This mismatch has raised the question, where does the missing glucose go if it is not metabolized oxidatively? We have previously demonstrated that an increased proportion of glucose is shunted through the pentose phosphate pathway prompting us to further investigate the total percentage of glucose metabolized by alternative pathways (the "missing glucose") in an attempt to understand the full milieu of altered or dysfunctional metabolism in the injured brain. ⋯ In addition to an overall depression of cerebral metabolism for oxygen and glucose, the percentage of glucose with alternative metabolic fates (missing glucose) was significantly higher in the posttraumatic brain than in the normal brain, almost a 3-fold elevation. Further study is needed to fully identify the alternative metabolic pathways involved.
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Microglia, the resident immune cells of the central nervous system, play a critical role in health and disease. Following injury, microglia upregulate inducible nitric oxide synthase (iNOS), and can exert neurotoxic effects by releasing large quantities of nitric oxide (NO). Expression of iNOS, and many other proinflammatory genes, is regulated in part by Ca influx and Ca-dependent transcription factors. The expression of the nonselective cation channel Sur1-Trpm4 may be 1 molecular mechanism by which microglia dynamically modulate Ca influx. We hypothesized that microglial Sur1-Trpm4 plays a role in microglial-mediated neuroinflammation by regulating the calcium-sensitive induction of iNOS. ⋯ Our results strongly support our hypothesis that Sur1-Trpm4 regulates the calcium-sensitive induction of iNOS by controlling NFAT activity. These observations have impactful therapeutic implications. Inhibition of Sur1-Trpm4 using the well-tolerated sulfonylurea glibenclamide (a.k.a. glyburide) may be a promising approach to limit the deleterious effects of microglial-mediated neuroinflammation.
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Intractable focal epilepsy is a devastating disorder with profound effects on cognition and quality of life. Epilepsy surgery can lead to seizure freedom in patients with focal epilepsy; however, sometimes it fails owing to an incomplete delineation of the epileptogenic zone (EZ). Brain networks in epilepsy can be studied with resting-state functional connectivity (RSFC) analysis, yet previous investigations using functional MRI or electrocorticography have produced inconsistent results. Magnetoencephalography (MEG) allows noninvasive whole-brain recordings, and can be used to study both long-range network disturbances in focal epilepsy and regional connectivity at the EZ. ⋯ Widespread global decreases in functional connectivity are observed in patients with focal epilepsy and may reflect deleterious long-term effects of recurrent seizures. Furthermore, enhanced regional functional connectivity at the area of resection may help predict seizure outcome and aid surgical planning.
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A constant conundrum for the surgical educator is the balancing act between resident training and patient safety. Surgical simulators have become attractive, allowing trainees to practice emerging skills without risking patient health. However, many surgical simulators are expensive, complex, and frequently do not offer realistic tissue or instrument manipulation. Residents typically understand the steps and anatomy of a procedure long before they develop the manual skills to perform the operation gracefully. It would therefore be valuable to develop simple surgical simulators that offer decreased complexity and faithfully reproduce the haptic experience of a given procedure. ⋯ Surgical skill simulation is an emerging technology and is useful for safe, effective resident training. However, much work in this field has focused on complex, expensive training models. Here, we demonstrate that surgical simulation can be simple, cheap, and provide realistic haptic feedback, and that residents improve both subjectively and objectively with our simulation platforms.