Emergence of exotic electronic and magnetic phases upon electron filling in Na2BO3 (B = Ta, Ir, Pt, and Tl): a first-principles study.

Competition between spin-orbit interaction and electron correlations can stabilize a variety of non-trivial electronic and magnetic ground states. Using density functional theory calculations, here we show that different exotic electronic and magnetic ground states can be obtained by electron filling of the B-site cation in the Na2BO3 family of compounds (B = Ta, Ir, Pt and Tl). Electron filling leads to a Peierls insulator state with a direct band gap to j = 1/2 spin-orbit assisted Mott-insulator to band insulator and then to negative charge-transfer half-metal transition. The magnetic ground state also undergoes a transition from a non-magnetic state to a zigzag antiferromagnetic state, a re-entrant non-magnetic state and finally to a ferromagnetic state. The electron localization function shows a ladder type dimerization or Peierls instability in Na2TaO3. Maximally localized Wannier function calculations reveal delocalization of electrons through the eg orbitals, which form a π bond, and localization of electrons through the t2g orbitals, which form a σ bond, between the neighbouring tantalum ions. Na2TlO3 shows Stoner or band ferromagnetism due to the localized moments with up-spin on oxygen ligands created by the negative charge-transfer character, interacting via the down-spin itinerant electrons of the Tl 5d-O 2p hybridized band. These findings are significant for practical applications; for instance the direct band gap insulator Na2TaO3 shows potential for utilisation in solar cells, while Na2TlO3, which exhibits ferromagnetic half metallicity, holds promise for spintronic device applications.

Evaluation and Characterization of Modified K114 Method to Localize Plaques in Rodent and Plaques and Tangles in Human Brain Tissue.

BACKGROUND: A plethora of studies has shown the utility of several chemical dyes due to their affinity to bind Aß to enable visualization of plaques under light or fluorescence microscope, and some of them showed affinity to bind neurofibrillary tangles (NFT) as well. However, only a few of them have the propensity to bind both senile plaques (SP) and NFT simultaneously. OBJECTIVE: In our current study, we aimed to modify the K114 dye and the staining procedure to substantially improve the staining of amyloid plaques in both human and rodent brains and neurofibrillary tangles in the human brain. METHODS: We modified the K114 solution and the staining procedure using Sudan Black as a modifier. Additionally, to evaluate the target of the modified K114, we performed double labeling of K114 and increased Aß against three different epitopes. We used 5 different antibodies to detect phosphorylated tau to understand the specific targets that modified K114 binds. RESULTS: Dual labeling using hyperphosphorylated antibodies against AT8, pTau, and TNT1 revealed that more than 80% hyperphosphorylated tau colocalized with tangles that were positive for modified K114, whereas more than 70% of the hyperphosphorylated tau colocalized with modified K114. On the other hand, more than 80% of the plaques that were stained with Aß MOAB-2 were colocalized with modified K114. CONCLUSION: Our modified method can label amyloid plaques within 5 min in the rat brain and within 20 min in the human brain. Our results indicated that modified K114 could be used as a valuable tool for detecting amyloid plaques and tangles with high contrast and resolution relative to other conventional fluorescence markers.

Insights into biomimetic system-ligand interaction of substituted isophthalic acid: A functionality induced photophysical study.

The present article attempts to interpret the modulation of photophysical properties of isophthalic acid (IPA) through its amino [5-amino isophthalic acid (5-amino IPA)] and azido [5-azido isophthalic acid (5-azido IPA)] substituted derivatives which are chemically potent organic ligands. The ground state structure-reactivity correlation of 5-amino IPA and 5-azido IPA has been deciphered through computational studies. The computed energetics show significant interaction feasibility of the substituted ligand systems with the biomimetic systems which is further validated experimentally. The binding interaction of the probes with oppositely polarized functionalization is studied to be significant with cetyltrimethylammonium bromide (CTAB) and bovine serum albumin (BSA) with the amino functionalized derivative having a comparatively stronger binding constant value. The steady-state absorption and fluorescence study establish significant modification of polarity of the heteronuclear probes. The micro polarity study in water-dioxane mixtures enables determination of polarity of 5-amino IPA in CTAB and BSA unlike 5-azido IPA. Presence of an overlapping region between the emission spectrum of BSA and the absorption spectrum of the probes as probable donor-acceptor pair are also scrutinized via the steady-state fluorescence studies. The photophysical behavior of 5-amino IPA is observed to be somewhat dissimilar to that of 5-azido IPA.

In vivo mapping of rat brain partial white matter content using hexachlorophene-induced neurotoxicity model.

Segmentation of the white matter in MRI scans of the rat brain presents a significant challenge due to the low contrast. Existing anatomical reference maps of rat brain are usually constructed from fixed tissue, which may suffer from geometrical distortions due to fixation/processing. To significantly increase the in vivo contrast between white and gray matter in the rat brain we used a known neurotoxicant hexachlorophene, which produces selective white matter damage. This model was used to map white matter in the rat brain and estimate the partial white matter content in any given imaging voxel. Hexachlorophene was administered to rats at a dose of 30 mg/kg orally once a day over five consecutive days. A significant white matter changes were observed using quantitative T2 maps, from which the partial white matter content throughout the whole rat brain was derived. Several assumptions were made: hexachlorophene affects T2 relaxation only in the white matter; T2 of gray matter is relatively uniform in the brain; apparent T2 value in a given voxel is a combination of T2s from white and gray matter portions of that voxel, hexachlorophene affects nearly 100 % of white matter. The partial white matter map of the rat brain was constructed with the resolution of 0.2 × 0.2 × 1.0 mm per voxel. This map could be adjusted for segmentation of the brain tissue with preset threshold of the white matter content, or to establish the tissue composition in any region of interest among other applications.

The role of astrocytes in the glymphatic network: a narrative review.

To date, treatment of Central Nervous System (CNS) pathology has largely focused on neuronal structure and function. Yet, revived attention towards fluid circulation within the CNS has exposed the need to further explore the role of glial cells in maintaining homeostasis within neural networks. In the past decade, discovery of the neural glymphatic network has revolutionized traditional understanding of fluid dynamics within the CNS. Advancements in neuroimaging have revealed alternative pathways of cerebrospinal fluid (CSF) generation and efflux. Here, we discuss emerging perspectives on the role of astrocytes in CSF hydrodynamics, with particular focus on the contribution of aquaporin-4 channels to the glymphatic network. Astrocytic structural features and expression patterns are detailed in relation to their function in maintaining integrity of the Blood Brain Barrier (BBB) as part of the neurovascular unit (NVU). This narrative also highlights the potential role of glial dysfunction in pathogenesis of neurodegenerative disease, hydrocephalus, intracranial hemorrhage, ischemic stroke, and traumatic brain injury. The purpose of this literature summary is to provide an update on the changing landscape of scientific theory surrounding production, flow, and absorption of cerebrospinal fluid. The overarching aim of this narrative review is to advance the conception of basic, translational, and clinical research endeavors investigating glia as therapeutic targets for neurological disease.

Combining tissue clearing and Fluoro-Jade C labeling for neurotoxicity assessments.

Tissue clearing refers to laboratory methods that make tissue transparent by chemical means. This approach allows the labeling, visualization, and analysis of specific targets without cutting the tissue into sections, thereby maintaining three-dimensional architecture. More than two dozen tissue-clearing methods have been developed by different research teams to date. While tissue clearing has been successfully applied in several studies concerning basic science or diseases, little is known about the utilization of tissue clearing for neurotoxicity evaluation. In this study, several tissue-clearing methods were combined with Fluoro-Jade C (FJ-C), a standard marker of neurodegeneration. The results suggest that some but not all tissue-clearing media are compatible with the FJ-C fluorophore. By utilizing a neurotoxicity animal model, the results further suggest that FJ-C labeling can be combined with tissue clearing for neurotoxicity assessments. This approach has the potential to be expanded further by combining multicolor labeling of molecular targets involved in the development and/or mechanisms of neurotoxicity and neurodegeneration.

Congenital myasthenic syndrome: a tale of two siblings.

Congenital myasthenic syndromes are a group of rare neuromuscular junction disorders. Traditional anticholinesterase inhibitors may not help in congenital myasthenic syndromes and in some variants may actually cause deterioration of symptoms. In this report, we describe a rare case of congenital myasthenic syndrome with heterozygous mutations in CHRNE gene (c.128A > T; heterozygous; exon 11) and COLQ gene (c.1201T > A; heterozygous; exon 16), which did not show improvement on neostigmine test but responded to treatment with oral salbutamol.

Assessment of sex-related neuropathology and cognitive deficits in the Tg-SwDI mouse model of Alzheimer's disease.

Cerebral amyloid angiopathy or CAA is a type of vascular dementia that can cause neuroinflammation, ischemia and hemorrhage, among other complications. CAA results from the deposition of amyloid beta (Aß) in blood vessels and is frequently observed in individuals with Alzheimer's disease (AD). One functional output of those pathological changes is measurable cognitive decline. Still not well understood, however, is the impact of gender or sex on the pathology of CAA, as well as CAA-induced cognitive decline. Here, we studied how sex impacts deposition of CAA-related pathology and the associated cognitive decline. We observed differential hippocampal pathology as far as regions of deposition, type of morphology, and total amount of pathology when assessing CAA pathology via (E,E)-1-fluoro-2,5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (FSB)-labeling, as well as neurodegeneration via Fluoro Jade C (FJC)-labeling, and lysosomal associated membrane protein deposition via LAMP-1 labeling. In accordance with other studies, our data suggest female TG-SwDI mice exhibit more severe pathological alterations in CAA pathology. Additionally, behavioral assessments revealed an impact of genotype that was more pronounced in TG-SwDI females. While the primary measure of learning and memory, the water maze, suggests an overall effect of genotype, effects in measures of locomotor activity and anxiety-like behavior suggest reduced habituation in females. This could be due to a lower retention for the tasks. Results of this study offer significant insight into the importance of examining effects of sex on CAA.

Simple and robust architecture of a laser system for atom interferometry.

We report a compact and robust architecture of a versatile laser system that allows the implementation of several advanced atom interferometry techniques, such as Bragg diffraction, Bloch oscillations, or single and double Raman diffraction. A low noise, frequency tunable fiber-laser (λ = ~1560 nm) serves as the seed. A couple of fiber-coupled amplifiers followed by two fibered second-harmonic generators produce a pair of phase-locked, frequency-controllable laser beams at 780 nm. Manipulating frequencies of individual laser beams at λ = 1560 nm before the amplifiers, facilitates achieving a maximum relative detuning of ± 20 MHz, while maintaining a constant output power. We present the scheme to implement Raman spectroscopy using our laser system and discuss its advantages. Finally, the overall performance of the laser setup has been evaluated by realizing interferometers in copropagating Ramsey-Raman and counterpropagating Bragg configuration.

Evaluation of Styrylbenzene analog- FSB and its affinity to bind parenchymal plaques and tangles in patients of Alzheimer's disease.

Although several histochemical markers for senile plaques (SP) and neurofibrillary tangles (NFTs) have been synthesized since the discovery of plaques in Alzheimer's disease (AD), only a handful of these markers stain both lesions in the human brain. Despite discovery of its ability to stain both SP and NFT over 13 years ago, the styrylbenzene derivative, (E,E)-1-fluoro-2,5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (FSB), has only recently gained attention, primarily due to its ability to function as a contrasting agent for MRI imaging of AD pathology in vivo. The structure of the compound is a nuclide with quantized angular momentum, which explains its value as a contrast agent. In the current study, modification of the established staining procedure produced meaningful improvement in the labeling of plaques and tangles in the human brain. We utilized two rodent models of AD to show FSB's value in labeling both Aß and tau lesions. Furthermore, our current modification allows us to detect SP in rodent brains in 15 min and both SP and NFT in human brains within 20 min. The study presents new evidence regarding potential binding targets for FSB as well as optimization protocols in which various parameters have been manipulated to show how section thickness, use of frozen versus paraffin-embedded sections, and selection of staining media can affect the intensity of the plaque and tangle staining in the brain. To determine the target FSB potentially binds, we performed double immunolabeling of FSB with mOC64 (a conformational antibody that label Aß1-42). Results indicated that all plaques in the brain colocalized with mOC64, suggesting that FSB has the potential to bind all Aß containing plaques, making it a very sensitive detector of multiple forms of SP... All antibodies were assessed for the degree of colocalization with FSB in order to better understand potential binding targets. We found more than 90% hyperphosphorylated Tau against AT8, AT180 and S214 colocalized with FSB labeled tangles. On the other hand, more than 90% of the mOC64 containing plaques colocalized with FSB stained plaques. Our results indicate that FSB is a valuable marker that can be used to detect AD pathologies in human and rodent brains with greater fluorescence intensity relative to other conventional fluorescence markers.

Tauroursodeoxycholic acid (TUDCA) is neuroprotective in a chronic mouse model of Parkinson's disease.

OBJECTIVE: Parkinson's disease (PD) is a progressive motor disease of unknown etiology. Although neuroprotective ability of endogenous bile acid, tauroursodeoxycholic acid (TUDCA), shown in various diseases, including an acute model of PD,the potential therapeutic role of TUDCA in progressive models of PD that exhibit all aspects of PD has not been elucidated. In the present study, mice were assigned to one of four treatment groups: (1) Probenecid (PROB); (2) TUDCA, (3) MPTP + PROB (MPTPp); and (3) TUDCA + MPTPp. Methods: Markers for dopaminergic function, neuroinflammation, oxidative stress and autophagy were assessed using high performance liquid chromatography (HPLC), immunohistochemistry (IHC) and western blot (WB) methods. Locomotion was measured before and after treatments. Results: MPTPp decreased the expression of dopamine transporters (DAT) and tyrosine hydroxylase (TH), indicating dopaminergic damage, and induced microglial and astroglial activation as demonstrated by IHC analysis. MPTPp also decreased DA and its metabolites as demonstrated by HPLC analysis. Further, MPTPp-induced protein oxidation; increased LAMP-1 expression indicated autophagy and the promotion of alpha-synuclein (α-SYN) aggregation. Discussion: Pretreatment with TUDCA protected against dopaminergic neuronal damage, prevented the microglial and astroglial activation, as well as the DA and DOPAC reductions caused by MPTPp. TUDCA by itself did not produce any significant change, with data similar to the negative control group. Pretreatment with TUDCA prevented protein oxidation and autophagy, in addition to inhibiting α-SYN aggregation. Although TUDCA pretreatment did not significantly affect locomotion, only acute treatment effects were measured, indicating more extensive assessments may be necessary to reveal potential therapeutic effects on behavior. Together, these results suggest that autophagy may be involved in the progression of PD and that TUDCA may attenuate these effects. The efficacy of TUDCA as a novel therapy in patients with PD clearly warrants further study.

The Mystery behind Dynamic Charge Disproportionation in BaBiO3.

BaBiO3(BBO) is known to be a valence-skipping perovskite, which avoids the metallic state through charge disproportionation (CD), the mechanism of which is still unresolved. A novel mechanism for CD is presented here in the covalent limit using a molecular orbital (MO) picture under two scenarios: (case i) Bi 6sp-O 2p and (case ii) Bi 6p-O 2p hybridizations that favor 5+ and 3+ states, respectively. The proposed model is further validated by using a combinatorial approach of X-ray spectroscopic experiments and first-principle calculations. The bulk X-ray photoemission spectrum reveals that, at room temperature, the CD is dynamic in nature, whereas, at 200 K, it approaches a quasi-static limit. Under compressive strain, the octahedral breathing mode is damped and drives the system to a quasi-static limit even at room temperature, giving rise to asymmetric CD.

Role of metals in Alzheimer's disease.

Metal homeostasis in the central nervous system (CNS) is a crucial component of healthy brain function, because metals serve as enzymatic cofactors and are key components of intra- and inter-neuronal signaling. Metal dysregulation wreaks havoc on neural networks via induction and proliferation of pathological pathways that cause oxidative stress, synaptic impairment, and ultimately, cognitive deficits. Thus, exploration of metal biology in relation to neurodegenerative pathology is essential in pursuing novel therapies for Alzheimer's Disease and other neurodegenerative disorders. This review covers mechanisms of action of aluminum, iron, copper, and zinc ions with respect to the progressive, toxic accumulation of extracellular ß-amyloid plaques and intracellular hyperphosphorylated neurofibrillary tau tangles that characterizes Alzheimer's Disease, with the goal of evaluating the therapeutic potential of metal ion interference in neurodegenerative disease prevention and treatment. As neuroscientific interest in the role of metals in neurodegeneration escalates-in large part due to emerging evidence substantiating the interplay between metal imbalances and neuropathology-it becomes clear that the use of metal chelating agents may be a viable method for ameliorating Alzheimer's Disease pathology, as its etiology remains obscure. We conclude that, although metal therapies can potentially deter neurodegenerative processes, the most promising treatments will remain elusive until further understanding of neurodegenerative etiology is achieved. New research directions may best be guided by animal models of neurodegeneration, which reveal specific insights into biological mechanisms underlying dementia.

Alzheimer's disease: a step closer to understanding type 3 diabetes in African Americans.

Alzheimer's disease (AD) is the fourth leading cause of death in the United States and the most common cause of adult-onset dementia. Recent results suggest an increased prevalence and severity in African Americans compared to Caucasians. Our understanding of the potential mechanism(s) underlying this ethnicity difference is limited. We previously described ethnicity-related differences in levels of neurodegenerative proteins and cytokines/chemokines in the BA21 region of African Americans and Caucasians with AD. Here, similar multiplex assays were used to examine those endpoints in patient postmortem cerebrospinal fluid (CSF). Additionally, we measured levels of C-peptide, ghrelin, gastric inhibitory polypeptide (GIP), glucagon-like peptide-1 (GLP-1), glucagon, insulin, leptin, PAI-1, resistin, and visfatin using a human diabetes 10-plex assay. The cytokine and chemokine assays revealed that levels of 26 chemokines or cytokines differed significantly with ethnicity, and three of those were significantly associated with gender. The neurodegenerative disease panel indicated that levels of soluble RAGE were significantly elevated in African Americans compared to Caucasians. All measures in the diabetes disease panel assay were significantly elevated in African Americans: ghrelin, GIP, GLP-1, glucagon, insulin, and visfatin. Through peripheral sample analysis, these results provide further evidence that ethnicity is critically involved in the manifestation of AD.

Global Neurotoxicity: Quantitative Analysis of Rat Brain Toxicity Following Exposure to Trimethyltin.

The organotin, trimethyltin (TMT), is a highly toxic compound. In this study, silver-stained rat brain sections were qualitatively and quantitatively evaluated for degeneration after systemic treatment with TMT. Degenerated neurons were counted using image analysis methods available in the HALO image analysis software. Specific brain areas including the cortex, inferior and superior colliculus, and thalamus were quantitatively analyzed. Our results indicate extensive and widespread damage to the rat brain after systemic administration of TMT. Qualitative results suggest severe TMT-induced toxicity 3 and 7 days after the administration of TMT. Trimethyltin toxicity was greatest in the hippocampus, olfactory area, cerebellum, pons, mammillary nucleus, inferior and superior colliculus, hypoglossal nucleus, thalamus, and cerebellar Purkinje cells. Quantification showed that the optic layer of the superior colliculus exhibited significantly more degeneration compared to layers above and below. The inferior colliculus showed greater degeneration in the dorsal area relative to the central area. Similarly, in cortical layers, there was greater neurodegeneration in deeper layers compared to superficial layers. Quantification of damage in various thalamic nuclei showed that the greatest degeneration occurred in midline and intralaminar nuclei. These results suggest selective neuronal network vulnerability to TMT-related toxicity in the rat brain.

In vivo demonstration of Congo Red labeled amyloid plaques via perfusion in the Alzheimer disease rat model.

BACKGROUND: Congo Red (CR) has been used for its binding affinity to amyloid fibrils for the better part of a century. Recently, our laboratory has demonstrated its ability to bind to tau protein as well. NEW METHOD: Here we describe a novel methodology for fast, thorough, whole-brain labeling of amyloid plaques with CR via perfusion. We tested five different variants which altered the volume of CR, the speed of perfusion, and the solution CR was solubilized in to determine the best results. RESULTS AND CONCLUSION: We determined that intra-cardiac perfusion of animals with 0.5 % CR in 100 ml of 50 % ethanol or perfusion with 0.5 of CR in 100 ml of 10 % neutral buffer formalin both perfused at a rate of 30 ml/min for 3.3 min resulted in the clearest CR labeling, with little to no background noise. Both variants were compatible with subsequent immunolabeling procedures for NU-1, as well as Ferritin and GFAP. Compared to traditional CR plaque labeling methodology, this new method allows for quick whole brain CR-labeling. This reduces the amount of time from days to mere minutes. It also reduces potential for variability that would result from staining slides in batches. Thus, CR-perfusion is a rapid, thorough method that can be utilized to rapidly stain amyloid in the rodent brain.

Modification of methods to use Congo-red stain to simultaneously visualize amyloid plaques and tangles in human and rodent brain tissue sections.

Although there are multiple histochemical tracers available to label plaques and tangles in the brain to evaluate neuropathology in Alzheimer disease (AD), few of them are versatile in nature and compatible with immunohistochemical procedures. Congo Red (CR) is an anisotropic organic stain discovered to label amyloid beta (Aß) plaques in the brain. Unfortunately, its use is underappreciated due to its low resolution and brightness as stated in previous studies using bright field microscopy. Here, we modified a previous method to localize both plaques and tangles in brains from humans and a transgenic rodent model of AD for fluorescence microscopic visualization. The plaque staining affinities displayed by CR were compared with fibrillar pattern labeling seen with Thioflavin S. This study summarizes the optimization of protocols in which various parameters have been finetuned. To determine the target CR potentially binds, we have performed double labeling with different antibodies against Aß as well as phosphorylated Tau. The plaque staining affinities exhibited by CR are compared with those associated with the diffuse pattern of labeling seen with antibodies directed against different epitopes of Aß. Neither CP13, TNT2 or TOC1 binds all the neurofibrillary tangles as revealed by CR labeling in the human brain. Additionally, we also evaluated double labeling with AT8, AT180, and PHF1. Interestingly, PHF-1 shows 40% colocalization and AT8 shows 15% colocalization with NFT. Thus, CR is a much better marker to detect AD pathologies in human and rodent brains with higher fluorescence intensity relative to other conventional fluorescence markers.

Quantitative Neurotoxicology: An Assessment of the Neurotoxic Profile of Kainic Acid in Sprague Dawley Rats.

This study consisted of a qualitative and quantitative assessment of neuropathological changes in kainic acid (KA)-treated adult male rats. Rats were administered a single 10 mg/kg intraperitoneal injection of KA or the same volume of saline and sacrificed 24 or 48 hours posttreatment. Brains were collected, sectioned coronally (∼ 81 slices), and stained with amino cupric silver to reveal degenerative changes. For qualitative assessment of neural degeneration, sectioned material was evaluated by a board-certified pathologist, and the level of degeneration was graded based upon a 4-point scale. For measurement of quantitative neural degeneration in response to KA treatment, the HALO digital image analysis software tool was used. Quantitative measurements of specific regions within the brain were obtained from silver-stained tissue sections with quantitation based on stain color and optical density. This quantitative evaluation method identified degeneration primarily in the cerebral cortex, septal nuclei, amygdala, olfactory bulb, hippocampus, thalamus, and hypothalamus. The KA-produced neuronal degeneration in the cortex was primarily in the piriform, insular, rhinal, and cingulate areas. In the hippocampus, the dentate gyrus was found to be the most affected area. Our findings indicate global neurotoxicity due to KA treatment. Certain brain structures exhibited more degeneration than others, reflecting differential sensitivity or vulnerability of neurons to KA.

Acetyl-l-carnitine does not prevent neurodegeneration in a rodent model of prolonged neonatal anesthesia.

Many studies have shown that prolonged or repeated use of general anesthesia early in life can cause an increase in neurodegeneration and lasting changes in behavior. While short periods of general anesthesia appear to be safe, there is a concern about the neurotoxic potential of prolonged or repeated general anesthesia in young children. Unfortunately, the use of general anesthesia in children cannot be avoided. It would be a great benefit to develop a strategy to reduce or reverse anesthesia mitigated neurotoxicity. The mechanisms behind anesthesia related neurotoxicity are unknown, but evidence suggests that mitochondrial dysfunction and abnormal energy utilization are involved. Recent research suggests that a class of compounds known as carnitines may be effective at preventing anesthesia related neurotoxicity by influencing fatty acid metabolism in the mitochondria. However, it is unknown if carnitines can provide protection against changes in behavior associated with early life exposure to anesthesia. Accordingly, we evaluated the neuroprotective potential of acetyl-l-carnitine in 7-day old rats. Rat pups were exposed to 6 h of general anesthesia with sevoflurane or a control condition, with and without acetyl-l-carnitine. The oxygenation level of animals was continuously monitored during sevoflurane exposure, and any animal showing signs of hypoxia was removed from the study. Animals exposed to sevoflurane showed clear signs of neurodegeneration 2 h after sevoflurane exposure. The hippocampus, cortex, thalamus, and caudate putamen all had elevated levels of Fluoro-Jade C staining. Despite the elevated levels of Fluoro-Jade C, few behavioral changes were observed in an independent cohort of animals treated with sevoflurane. Furthermore, acetyl-l-carnitine had little impact on levels of Fluoro-Jade C staining in animals treated with sevoflurane. These data suggest that acetyl-l-carnitine may offer little protection again anesthesia related neurotoxicity in fully oxygenated animals.