- Intracarotid amobarbital disrupts synchronous and nested oscillatory activity ipsilateral to injection. [Journal Article]
- EBEpilepsy Behav Case Rep 2018; 10:25-28
- The mechanism of amobarbital action during the intracarotid amobarbital procedure is poorly understood. We report a patient case who underwent IAP while implanted with bilateral stereo-EEG. We analyz...
The mechanism of amobarbital action during the intracarotid amobarbital procedure is poorly understood. We report a patient case who underwent IAP while implanted with bilateral stereo-EEG. We analyzed the spectral power, phase amplitude coupling, and cluster-phase group synchrony during the procedure. Delta and gamma power increased bilaterally. By contrast, phase amplitude coupling increased only ipsilateral to the injection. Similarly, 4-30 Hz cluster-phase group synchrony declines and gamma cluster-phase group synchrony increases only ipsilateral to the injection. These results suggest that a possible additional mechanism for amobarbital action in the IAP is by altering the precise timing of oscillatory activity.
- A simple magnetoencephalographic auditory paradigm may aid in confirming left-hemispheric language dominance in epilepsy patients. [Journal Article]
- PlosPLoS One 2018; 13(7):e0200073
- CONCLUSIONS: This simple MEG paradigm shows promise in feasibly and noninvasively confirming left-hemispheric language dominance in epilepsy surgery candidates. It may aid in reducing the need for the IAP, if the results are confirmed in larger patient samples.
- StatPearls [BOOK]
- BOOKStatPearls Publishing: Treasure Island (FL)
- Barbiturates are a class of sedative-hypnotic drugs. They are commonly used as antiepileptics (phenobarbital) and for the induction of general anesthesia (thiopental). Some states administer barbitur...
Barbiturates are a class of sedative-hypnotic drugs. They are commonly used as antiepileptics (phenobarbital) and for the induction of general anesthesia (thiopental). Some states administer barbiturates for physician-assisted suicide/euthanasia and use them for capital punishment by lethal injection. Their use in clinical practice has largely been replaced by benzodiazepines such as alprazolam, diazepam, and lorazepam due to the lower risk of overdose and available antidote to reverse toxicity. Barbiturates are used as a laboratory buffer and can be found in clinical and research laboratories. Barbiturates are controlled substances that pose a high risk for abuse given their psychoactive effects. Restrictions on access to barbiturates have caused the number of overdoses to decline. Common barbiturates include the following: Methohexital and thiopental are used as anesthetics. Phenobarbital and primidone are used in the treatment of seizures. Amobarbital is used as an investigative agent in the Wada test (neurological assessment of cerebral hemispheres) Butalbital, in combination with other medications, is used for headaches and muscle pain.
- Neuropsychology Within a Tertiary Care Epilepsy Center. [Review]
- ACArch Clin Neuropsychol 2018 May 01; 33(3):354-364
- Epilepsy is a prevalent condition characterized by variations in its clinical presentation, etiology, and amenability to treatment. Through history, neuropsychologists have played a significant role ...
Epilepsy is a prevalent condition characterized by variations in its clinical presentation, etiology, and amenability to treatment. Through history, neuropsychologists have played a significant role in performing research studies on changes in language, memory, and executive functioning in patients with epilepsy, including those undergoing surgical treatment for medically refractory seizures. These studies provided a foundation for establishing neuropsychologists as critical members of interdisciplinary clinical teams specializing in evaluation and treatment of epilepsy. This article describes a number of elements of specialized neuropsychological practice that have evolved over the years within a tertiary care epilepsy center. Through diagnostic interview and objective testing, the neuropsychologist is able to provide a more complete and objective understanding of a patient's cognitive and behavioral functioning than what is obtained by other clinicians through brief office visits. While assessment of cognition, mood, and behavior is the most commonly provided service to patients with epilepsy from all age groups, there are many instances when neuropsychologists in surgical settings are called to perform more specialized procedures, including the intracarotid amytal (Wada) procedure, electrocortical stimulation mapping of language eloquent brain regions, and functional brain imaging procedures. While working as a neuropsychologist on an interdisciplinary epilepsy care team requires specialized knowledge and clinical training, it is extremely satisfying due to the diversity of the patient population and the particular challenges resulting from the often unique manner that cognition and behavior can be affected in patients with epilepsy across the lifespan.
- Provocative Testing Prior to Anterior Cerebral Artery Fusiform Aneurysm Embolization. [Journal Article]
- INInterv Neurol 2018; 7(1-2):36-41
- We report 2 cases of parent artery occlusion (PAO) for anterior cerebral artery (ACA) fusiform aneurysm embolization after superselective provocative testing was performed to confirm distal territory...
We report 2 cases of parent artery occlusion (PAO) for anterior cerebral artery (ACA) fusiform aneurysm embolization after superselective provocative testing was performed to confirm distal territory viability. The first case involves a patient in the second decade of life who presented with subarachnoid hemorrhage and underwent PAO after a balloon test occlusion in the distal ACA revealed no neurophysiology changes. The second case involves another patient in the forth decade of life who presented with an enlarging pseudoaneurysm and underwent PAO after a sodium amobarbital infusion in the distal ACA revealed no clinical change. Both patients tolerated PAO without clinical compromise. PAO after provocative testing may be a safe and effective strategy in the management of fusiform aneurysm treatment.
- Targeting mitochondrial responses to intra-articular fracture to prevent posttraumatic osteoarthritis. [Journal Article]
- STSci Transl Med 2018 Feb 07; 10(427)
- We tested whether inhibiting mechanically responsive articular chondrocyte mitochondria after severe traumatic injury and preventing oxidative damage represent a viable paradigm for posttraumatic ost...
We tested whether inhibiting mechanically responsive articular chondrocyte mitochondria after severe traumatic injury and preventing oxidative damage represent a viable paradigm for posttraumatic osteoarthritis (PTOA) prevention. We used a porcine hock intra-articular fracture (IAF) model well suited to human-like surgical techniques and with excellent anatomic similarities to human ankles. After IAF, amobarbital or N-acetylcysteine (NAC) was injected to inhibit chondrocyte electron transport or downstream oxidative stress, respectively. Effects were confirmed via spectrophotometric enzyme assays or glutathione/glutathione disulfide assays and immunohistochemical measures of oxidative stress. Amobarbital or NAC delivered after IAF provided substantial protection against PTOA at 6 months, including maintenance of proteoglycan content, decreased histological disease scores, and normalized chondrocyte metabolic function. These data support the therapeutic potential of targeting chondrocyte metabolism after injury and suggest a strong role for mitochondria in mediating PTOA.
- Intermediary metabolism and fatty acid oxidation: novel targets of electron transport chain-driven injury during ischemia and reperfusion. [Journal Article]
- AJAm J Physiol Heart Circ Physiol 2018 Apr 01; 314(4):H787-H795
- Cardiac ischemia-reperfusion (I/R) damages the electron transport chain (ETC), causing mitochondrial and cardiomyocyte injury. Reversible blockade of the ETC at complex I during ischemia protects the...
Cardiac ischemia-reperfusion (I/R) damages the electron transport chain (ETC), causing mitochondrial and cardiomyocyte injury. Reversible blockade of the ETC at complex I during ischemia protects the ETC and decreases cardiac injury. In the present study, we used an unbiased proteomic approach to analyze the extent of ETC-driven mitochondrial injury during I/R. Isolated-perfused mouse (C57BL/6) hearts underwent 25-min global ischemia (37°C) and 30-min reperfusion. In treated hearts, amobarbital (2 mM) was given for 1 min before ischemia to rapidly and reversibly block the ETC at complex I. Mitochondria were isolated at the end of reperfusion and subjected to unbiased proteomic analysis using tryptic digestion followed by liquid chromatography-mass spectrometry with isotope tags for relative and absolute quantification. Amobarbital treatment decreased cardiac injury and protected respiration. I/R decreased the content ( P < 0.05) of multiple mitochondrial matrix enzymes involved in intermediary metabolism compared with the time control. The contents of several enzymes in fatty acid oxidation were decreased compared with the time control. Blockade of ETC during ischemia largely prevented the decreases. Thus, after I/R, not only the ETC but also multiple pathways of intermediary metabolism sustain damage initiated by the ETC. If these damaged mitochondria persist in the myocyte, they remain a potent stimulus for ongoing injury and the transition to cardiomyopathy during prolonged reperfusion. Modulation of ETC function during early reperfusion is a key strategy to preserve mitochondrial metabolism and to decrease persistent mitochondria-driven injury during longer periods of reperfusion that predispose to ventricular dysfunction and heart failure. NEW & NOTEWORTHY Ischemia-reperfusion (I/R) damages mitochondria, which could be protected by reversible blockade of the electron transport chain (ETC). Unbiased proteomics with isotope tags for relative and absolute quantification analyzed mitochondrial damage during I/R and found that multiple enzymes in the tricarboxylic acid cycle, fatty acid oxidation, and ETC decreased, which could be prevented by ETC blockade. Strategic ETC modulation can reduce mitochondrial damage and cardiac injury.
- The safety and efficacy of propofol as a replacement for amobarbital in intracarotid Wada testing of presurgical patients with epilepsy. [Journal Article]
- EBEpilepsy Behav 2018; 78:25-29
- The intracarotid sodium amytal procedure (the "Wada test") has for many years been the gold standard for language and memory lateralization and remains an important part of presurgical analysis for p...
The intracarotid sodium amytal procedure (the "Wada test") has for many years been the gold standard for language and memory lateralization and remains an important part of presurgical analysis for patients with medically intractable seizures. Due to shortages in the key sedative (amobarbital), neuropsychologists have turned to alternatives such as propofol. Our aim was to investigate the safety and efficacy of propofol relative to amobarbital in the Wada test.
- Inhibition of mitochondrial complex I improves glucose metabolism independently of AMPK activation. [Journal Article]
- JCJ Cell Mol Med 2018; 22(2):1316-1328
- Accumulating evidences showed metformin and berberine, well-known glucose-lowering agents, were able to inhibit mitochondrial electron transport chain at complex I. In this study, we aimed to explore...
Accumulating evidences showed metformin and berberine, well-known glucose-lowering agents, were able to inhibit mitochondrial electron transport chain at complex I. In this study, we aimed to explore the antihyperglycaemic effect of complex I inhibition. Rotenone, amobarbital and gene silence of NDUFA13 were used to inhibit complex I. Intraperitoneal glucose tolerance test and insulin tolerance test were performed in db/db mice. Lactate release and glucose consumption were measured to investigate glucose metabolism in HepG2 hepatocytes and C2C12 myotubes. Glucose output was measured in primary hepatocytes. Compound C and adenoviruses expressing dominant negative AMP-activated protein kinase (AMPK) α1/2 were exploited to inactivate AMPK pathway. Cellular NAD+ /NADH ratio was assayed to evaluate energy transforming and redox state. Rotenone ameliorated hyperglycaemia and insulin resistance in db/db mice. It induced glucose consumption and glycolysis and reduced hepatic glucose output. Rotenone also activated AMPK. Furthermore, it remained effective with AMPK inactivation. The enhanced glycolysis and repressed gluconeogenesis correlated with a reduction in cellular NAD+ /NADH ratio, which resulted from complex I suppression. Amobarbital, another representative complex I inhibitor, stimulated glucose consumption and decreased hepatic glucose output in vitro, too. Similar changes were observed while expression of NDUFA13, a subunit of complex I, was knocked down with gene silencing. These findings reveal mitochondrial complex I emerges as a key drug target for diabetes treatment. Inhibition of complex I improves glucose homoeostasis via non-AMPK pathway, which may relate to the suppression of the cellular NAD+ /NADH ratio.
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- Assessment of grammar optimizes language tasks for the intracarotid amobarbital procedure. [Journal Article]
- EBEpilepsy Behav 2017; 76:89-100
- CONCLUSIONS: The results may be significant for individuals with epilepsy undergoing IAP. The grammar tests may be a highly efficient measure for lateralizing language function in the recovery phase.