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Background: Strengthening exercise for gluteus medius (GMed) is an important management strategy for lower limb disorders such as osteoarthritis and patello-femoral syndrome, and exercises in functional positions are commonly prescribed. Electromyography (EMG) can be used to measure muscle activation to ascertain the extent of muscle recruitment during exercise. Objectives: To review the available evidence on the magnitude of GMed activation measured with EMG during therapeutic exercise. Methods: A structured review of studies which measured EMG magnitude of GMed during a range of therapeutic exercises was undertaken. Amplitude levels of GMed were reported as a percentage of maximum voluntary isometric contraction. Results: Fifteen studies were included. Most of these were conducted on asymptomatic volunteers, with three studies investigating individuals with knee or hip pathology. A wide range of exercises was investigated in both weightbearing (WB) and nonweightbearing (NWB) positions. In general, EMG activation was greater in WB positions but variation occurred across studies. Many exercises were below levels considered necessary for strength gains. Generally, methodological quality was good but there was variation in the reporting of technical aspects of the study. Many of the studies did not acknowledge the range of limitations of EMG in measuring muscle activation in therapeutic exercise. Conclusions: The results provide some information regarding GMed recruitment during exercise, although there were some discrepancies in results between studies which may be due to factors related to EMG measurement and recording as well as the execution of the exercise. Extrapolation of results to symptomatic populations in a clinical setting islimited. [ABSTRACT FROM AUTHOR]

Prolonged seizures (status epilepticus) are associated with brain region-specific regulation of apoptosis-associated signaling pathways. Bcl-2 homology domain 3-only (BH3) members of the Bcl-2 gene family are of interest as possible initiators of mitochondrial dysfunction and release of apoptogenic molecules after seizures. Previously, we showed that expression of the BH3-only protein, Bcl-2 interacting mediator of cell death (Bim), increased in the rat hippocampus but not in the neocortex after focal-onset status epilepticus. In this study, we examined Bim expression in mice and compared seizure damage between wild-type and Bim-deficient animals. Status epilepticus induced by intra-amygdala kainic acid (KA) caused extensive neuronal death within the ipsilateral hippocampal CA3 region. Hippocampal activation of factors associated with transcriptional and posttranslational activation of Bim, such as CHOP and c-Jun NH(2)-terminal kinases, was significant within 1 h. Upregulation of bim mRNA was evident after 2 h and Bim protein increased between 4 and 24 h. Hippocampal CA3 neurodegeneration was reduced in Bim-deficient mice compared with wild-type animals after seizures in vivo, and short interfering RNA molecules targeting bim reduced cell death after KA treatment of hippocampal organotypic cultures. In contrast, neocortical Bim expression declined after status epilepticus, and neocortex damage in Bim-deficient mice was comparable with that in wild-type animals. These results show region-specific differential contributions of Bim to seizure-induced neuronal death. [ABSTRACT FROM AUTHOR]

Hydrophilic/oleophobic surfaces are desirable in many applications including self-cleaning, antifogging, oil-water separation, etc. However, making plastic surfaces hydrophilic/oleophobic is challenging due to the intrinsic hydrophobicity/oleophilicity of plastics. Here, we report a simple and effective method of making plastics hydrophilic/oleophobic. Plastics, including poly (methyl methacrylate) (PMMA), polystyrene (PS), and polycarbonate (PC), have been coated with a perfluoropolyether (PFPE) (i.e., commercially known as Zdol) via dip coating and then irradiated with UV/Ozone. The contact angle measurements indicate that the treated plastics have a lower water contact angle (WCA) and higher hexadecane contact angle (HCA), i.e., they are simultaneously hydrophilic/oleophobic. The Fourier transform infrared (FTIR) results suggest that UV/Ozone treatment introduces oxygen-containing polar groups on the plastic surfaces, which renders the plastic surfaces hydrophilic. Meanwhile, more orderly packed PFPE Zdol molecules, which is due to the UV-induced bonding between PFPE Zdol and the plastic surface, result in the oleophobicity. Moreover, the simultaneous hydrophilicity/oleophobicity of functionalized plastics does not degrade in aging tests, and they have superior antifogging performance and detergent-free cleaning capability. This simple method developed here potentially can be applied to other plastics and has important implications in the functionalization of plastic surfaces.

Purpose of Review: The purpose of this review is to discuss treatment options, rehabilitation protocols, return-to-play criteria, and expected outcomes after non-operative and operative treatment of anterior cruciate ligament (ACL) tears among an athletic population., Recent Findings: Non-operative treatment may be a viable option for some athletes with an ACL tears but can be difficult to predict "copers," and those that resume to sports return at lower performance level and/or less intense activities. Most studies assessing function after ACL reconstruction demonstrate favorable outcomes using patient-reported outcome studies. However, return-to-play and graft re-rupture rates vary substantially based on patient characteristics and level and type of athletic activity. Grafts used to reconstruct ACL produce similar objective outcomes and favorable patient-reported outcomes but have variable re-rupture rates depending on study and differ largely on morbidity associated with graft harvest. Various treatment methods including non-operative and operative techniques have been demonstrated to be efficacious in returning athletes to athletic activity depending on patient age and level of activity. Adherence to fundamental rehabilitation principles and accepted return-to-play guidelines can optimize outcomes and limit re-injury to the injured or contralateral limb., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The 35th Annual Advances in Contrast Ultrasound International Bubble Conference convened in Chicago, IL, USA, on September 30th to October 1st, 2021. It featured a range of novel research from animal studies to clinical applications in multiple organ systems, demonstrating the utility of contrast enhanced ultrasound (CEUS). A multidisciplinary group of experts on the use of CEUS, including physicians, basic scientists, engineers, and industry partners, convened to discuss cutting edge research and new applications for CEUS. The conference demonstrated the wide range of CEUS uses and potential uses, including cardiac risk stratification, sonothrombolysis, peripheral vascular reperfusion, liver and renal mass evaluation, lymphatic evaluation, sentinel node identification, and CEUS use in pediatrics. The International Contrast Ultrasound Society uses this information to continue advocating for the safe and appropriate use of CEUS., (© 2022. The Author(s).)

Background: Sporadic school closures and a shift to online teaching have resulted in significant work changes for teachers in Ireland during the COVID-19 pandemic. Such rapid changes are likely to compound other personal or family stressors resultant from the pandemic., Method: This study examines occupational stress levels during COVID-19 amongst a national sample of 245 teachers in Ireland using the Copenhagen Burnout Inventory as the main outcome measure., Results: Moderate or high levels of personal burnout was reported by 82% ( n  = 202) of the sample and 79% ( n  = 193) reported work burnout. COVID-19 related adverse effects were reported by teachers on physical (43%) and mental health (67%), with deterioration in eating (34%), sleeping (70%) and alcohol use (33%). 100 (42%) participants felt unable to keep safe at work. Low levels of job satisfaction were present (66%), negatively correlating with burnout scores (r s= -0.405, p <.01). 142 (58%) teachers had seriously considered changing jobs in the previous 6-12 months., Conclusion: Plans for continued educational access for students must urgently include interventions optimising the occupational environment and resources for teachers. This is necessary to prevent the deleterious impact of personal burnout on teacher wellbeing and to minimise the likelihood of increased staff turnover, early retirement and adverse impacts on teaching quality relating to work burnout., Competing Interests: The authors have no conflicts of interest to disclose, (© 2021 The Authors. Published by Elsevier Ltd.)

Background: The teaching profession was dramatically affected by COVID-19 with school closures and ultimately the move to online learning. COVID-19 brought additional stress to an already demanding profession with the introduction of online teaching, teachers experiencing fear of infection and additional workloads accompanying the pandemic., Aim: To examine COVID-19 related occupational stress in teachers in Ireland through a qualitative study using a thematic analysis approach., Method: This study implemented two recruitment strategies for participants; email invitations to all members of ILSA and INTO, and email invitations with study information to school principals. A study specific questionnaire was devised with three questions offering free text responses. All responses were anonymous and analysed collectively. The Braun and Clarke thematic analysis method was employed to analyse participants' responses., Results: 224 participants responded to the survey, however not all participants completed all three questions. Initially 98 codes were generated from the data set, and subsequently reduced to 41 final codes. The codes were arranged into three final themes; Overburdened, Abandoned, and Consequences, representing occupational stress in teachers during COVID-19., Conclusion: In the form of the three themes identified, participants described issues such as large class sizes, high workload, and out of work hours contact, among others. These issues contributed negatively to participants' mental health and wellbeing with descriptions of being exhausted, isolated, stressed and experiencing burnout. Ensuring adequate awareness of, and paying attention to, teacher wellbeing is essential, such that optimisation of school environment can occur in light of additional burden associated with COVID-19., Competing Interests: The authors have no conflicts of interest to disclose., (© 2022 The Authors.)

Purpose of Review: Anterior cruciate ligament reconstruction is one of the most common orthopedic procedures performed, accounting for over 200,000 cases annually. Despite the high prevalence, there is still much debate as to the optimal graft choice. The purpose of this review is to evaluate the current literature and discuss the reported outcomes for the most common graft choices., Recent Findings: The most common autografts being used include bone-patellar tendon-bone (BPTB), hamstring tendon (HT), and quadriceps tendon (QT). Hamstring tendon might have a slightly higher re-tear rate when compared with BPTB (2.84 versus 2.80). However, BPTB has a higher rate of anterior knee and kneeling pain in the short- and mid-term follow-up. This has not been shown to be the case in long-term follow-up. Allograft is a viable option for revisions and primaries in patients greater than 35 years old; however, re-tear rate increases significantly in younger patients. ACL reconstruction graft choice is a highly studied and yet still exceedingly debated topic. Most large studies report either no significant difference or a small difference in failure rate and outcome scores between the different autograft choices. Allografts have been demonstrated to have an increased risk of failure in younger athletes and should be reserved for revision cases and those aged 35 years and older. Graft choice should ultimately be decided upon based on surgeon comfort and experience and individual patient characteristics.

Glycogen synthase kinase-3 (GSK-3) is ubiquitously expressed throughout the brain and involved in vital molecular pathways such as cell survival and synaptic reorganization and has emerged as a potential drug target for brain diseases. A causal role for GSK-3, in particular the brain-enriched GSK-3β isoform, has been demonstrated in neurodegenerative diseases such as Alzheimer's and Huntington's, and in psychiatric diseases. Recent studies have also linked GSK-3 dysregulation to neuropathological outcomes in epilepsy. To date, however, there has been no genetic evidence for the involvement of GSK-3 in seizure-induced pathology. Status epilepticus (prolonged, damaging seizure) was induced via a microinjection of kainic acid into the amygdala of mice. Studies were conducted using two transgenic mouse lines: a neuron-specific GSK-3β overexpression and a neuron-specific dominant-negative GSK-3β (GSK-3β-DN) expression in order to determine the effects of increased or decreased GSK-3β activity, respectively, on seizures and attendant pathological changes in the hippocampus. GSK-3 inhibitors were also employed to support the genetic approach. Status epilepticus resulted in a spatiotemporal regulation of GSK-3 expression and activity in the hippocampus, with decreased GSK-3 activity evident in non-damaged hippocampal areas. Consistent with this, overexpression of GSK-3β exacerbated status epilepticus-induced neurodegeneration in mice. Surprisingly, decreasing GSK-3 activity, either via overexpression of GSK-3β-DN or through the use of specific GSK-3 inhibitors, also exacerbated hippocampal damage and increased seizure severity during status epilepticus. In conclusion, our results demonstrate that the brain has limited tolerance for modulation of GSK-3 activity in the setting of epileptic brain injury. These findings caution against targeting GSK-3 as a treatment strategy for epilepsy or other neurologic disorders where neuronal hyperexcitability is an underlying pathomechanism.

Background: Pacemakers (PM) are used for managing sick sinus syndrome (SSS). This study evaluates predictors and trends of PM implantation for SSS., Methods: Patients were identified from the National Inpatient Sample dataset (2003-2013). Included patients were ≥18 years old, had a diagnosis of sinus node dysfunction and atrial arrhythmia (i.e., SSS). Patients who died, transferred out, who had prior device, or had a defibrillator or resynchronization therapy device implanted were excluded. Included patients were then stratified by if a PM was implanted. Data regarding SSS, trends of PM utilization, and multivariable models of factors associated with PM implantation are presented., Results: Note that 328,670 patients satisfied study criteria. This study compared patients who underwent (87.4%) PM implantation to those who did not undergo (12.6%) PM implantation. The annual trends for hospitalization with SSS and PM placement have been decreasing (P <0.001). Variables associated with lower likelihood for PM implantation include young age, female sex, non-Caucasian race, chronic heart failure, Charlson Comorbidity Score ≥1, emergency room and weekend admission, hospital stay ≤3 days, and high cardiology inpatient volume. Greater likelihood for PM implantation was associated with hyperlipidemia, hypertension, and hospitals that were either private, large, Northeastern location, or with high cardiac procedural volume., Conclusions: Analyzing 11-year data from a national inpatient database demonstrate a number of relevant variables that impact PM utilization that include not only clinical but also nonclinical variables such as socioeconomic status, gender, and hospital features. Racial and gender bias toward PM implantation are unchanged and persist through 2013., (© 2017 Wiley Periodicals, Inc.)

Seizures are common during the neonatal period, often due to hypoxic-ischemic encephalopathy and may contribute to acute brain injury and the subsequent development of cognitive deficits and childhood epilepsy. Here we explored short- and long-term consequences of neonatal hypoxia-induced seizures in 7 day old C57BL/6J mice. Seizure activity, molecular markers of hypoxia and histological injury were investigated acutely after hypoxia and response to chemoconvulsants and animal behaviour was explored at adulthood. Hypoxia was induced by exposing pups to 5% oxygen for 15 min (global hypoxia). Electrographically defined seizures with behavioral correlates occurred in 95% of these animals and seizures persisted for many minutes after restitution of normoxia. There was minimal morbidity or mortality. Pre- or post-hypoxia injection of phenobarbital (50mg/kg) had limited efficacy at suppressing seizures. The hippocampus from neonatal hypoxia-seizure mice displayed increased expression of vascular endothelial growth factor and the immediate early gene c-fos, minimal histological evidence of cell injury and activation of caspase-3 in scattered neurons. Behavioral analysis of mice five weeks after hypoxia-induced seizures detected novel anxiety-related and other behaviors, while performance in a spatial memory test was similar to controls. Seizure threshold tests with kainic acid at six weeks revealed that mice previously subject to neonatal hypoxia-induced seizures developed earlier, more frequent and longer-duration seizures. This study defines a set of electro-clinical, molecular, pharmacological and behavioral consequences of hypoxia-induced seizures that indicate short- and long-term deleterious outcomes and may be a useful model to investigate the pathophysiology and treatment of neonatal seizures in humans., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Status epilepticus in the adult brain invariably causes an increase in hippocampal neurogenesis and the appearance of ectopic cells and this has been implicated as a causal factor in epileptogenesis. The effect of status epilepticus on neurogenesis in the developing brain is less well characterized and models of early-life seizures typically do not reproduce the hippocampal damage common to human mesial temporal sclerosis. We recently reported that evoking status epilepticus by intra-amygdala microinjection of kainic acid in post-natal (P) day 10 rats caused substantial acute neuronal death within the ipsilateral hippocampus and rats later developed unilateral hippocampal sclerosis and spontaneous recurrent seizures. Here, we examined the expression of a selection of genes associated with neurogenesis and assessed neurogenic function in this model. Protein levels of several markers of neurogenesis including polysialic acid neural cell adhesion molecule, neuroD and doublecortin were reduced in the hippocampus three days after status epilepticus in P10 rats. In contrast, protein levels of neurogenesis markers were similar to control in rats at P55. Pulse-chase experiments using thymidine analogues suggested there was a reduction in new neurons at 72 h after status epilepticus in P10 rats, whereas numbers of new neurons labelled in epileptic rats at P55 with hippocampal sclerosis were similar to controls. The present study suggests that status epilepticus in the immature brain suppresses neurogenesis but the neurogenic potential is retained in animals that later develop hippocampal sclerosis.

FOXO3a is member of the Forkhead box class O transcription factors, which functions in diverse pathways to regulate cellular metabolism, differentiation, and apoptosis. FOXO3a shuttles between the cytoplasm and nucleus and may be activated in neurons by stressors, including seizures. A subset of nuclear transcription factors may localize to mitochondria, but whether FOXO3a is present within brain mitochondria is unknown. Here, we report that purified mitochondrial fractions from rat, mouse, and human hippocampus, as well as HT22 hippocampal cells, contain FOXO3a protein. Immunogold electron microscopy supported the presence of FOXO3a within brain mitochondria, and chromatin immunoprecipitation analysis suggested FOXO3a was associated with mitochondrial DNA. Over-expression of a mitochondrially targeted FOXO3a fusion protein in HT22 cells, but not primary hippocampal neurons, conferred superior protection against glutamate toxicity than FOXO3a alone. Mitochondrial FOXO3a levels were reduced in the damaged region of the mouse hippocampus after status epilepticus, while mitochondrial fractions from the hippocampus of patients with temporal lobe epilepsy displayed higher levels of FOXO3a than controls. These results support mitochondria as a site of FOXO3a localization, which may contribute to the overall physiological and pathophysiological functions of this transcription factor., (© 2012 International Society for Neurochemistry.)

Dopamine D2 receptor (D2R) signalling has been shown to modulate seizure-induced hippocampal cell death. D2R knockout (D2R-/-) mice are more susceptible to kainic acid (KA)-induced excitotoxicity, displaying cell death in the CA3 subfield of the hippocampus at KA doses not damaging in wild-type (WT) animals. Absence of D2R signalling in the hippocampus leads to activation (dephosphorylation) of glycogen synthase kinase 3β (GSK-3β) after KA (20 mg/kg), which is not associated with a change in the phosphorylation of the GSK-3β regulator Akt at the canonical threonine 308 residue. In the present study, we investigated alternative pathways responsible for the activation of GSK-3β in the hippocampus of the D2R-/- mice 24 h following KA-induced seizures. Here, we show that phosphorylation of Akt occurs at serine 473 (Ser473) in the CA3 region of WT but not D2R-/- mice following KA. Moreover, the CA1 subregion, which does not undergo neurodegeneration in either WT or D2R-/- mice, displays a strong induction of Akt (Ser473) phosphorylation after KA. Additionally, the vulnerability in the CA3 is not associated with changes to p38MAPK and Dishevelled activation, and β-catenin does not appear to be a downstream target of the GSK-3β. Thus, we propose that GSK-3β phosphorylation-mediated hippocampal cell survival may depend on Akt (Ser473) phosphorylation; loss of D2R-mediated signalling in the CA3 region of D2R-/- mice leads to reduced Akt (Ser473) phosphorylation rendering neurons more vulnerable to apoptosis. Further investigation is required to fully elucidate the GSK-3β targets involved in D2R-dependent response to excitotoxicity.

Autism spectrum disorders (ASD) and epilepsy are very common neurological disorders of childhood, with an estimated incidence of about 0.5 - 1 % in worldwide population. ASD and epilepsy are often associated, suggesting that common neurodevelopmental bases may exist for these two disorders. The neurodevelopmental bases of both ASD and epilepsy have been clearly showed by a number of genetic, neuroimaging and neuropathological studies. In recent years, dysfunction of inhibitory GABAergic circuits has been proposed as a cause for both disorders. Several studies performed on both animal models and postmortem human samples indicate that GABAergic neurons and circuits are altered in both ASD and epilepsy, suggesting that the excitation/inhibition imbalance resulting from neurodevelopmental defects in GABAergic circuitry might represent a common pathogenetic mechanism for these disorders. Here, we will review the most significant studies supporting this hypothesis.

Epilepsy is a complex disease, characterized by the repeated occurrence of bursts of electrical activity (seizures) in specific brain areas. The behavioral outcome of seizure events strongly depends on the brain regions that are affected by overactivity. Here we review the intracellular signaling pathways involved in the generation of seizures in epileptogenic areas. Pathways activated by modulatory neurotransmitters (dopamine, norepinephrine, and serotonin), involving the activation of extracellular-regulated kinases and the induction of immediate early genes (IEGs) will be first discussed in relation to the occurrence of acute seizure events. Activation of IEGs has been proposed to lead to long-term molecular and behavioral responses induced by acute seizures. We also review deleterious consequences of seizure activity, focusing on the contribution of apoptosis-associated signaling pathways to the progression of the disease. A deep understanding of signaling pathways involved in both acute- and long-term responses to seizures continues to be crucial to unravel the origins of epileptic behaviors and ultimately identify novel therapeutic targets for the cure of epilepsy.

Activation of dopamine D1 receptors (D1Rs) has been shown to induce epileptiform activity. We studied the molecular changes occurring in the hippocampus in response to the administration of the D1-type receptor agonist, SKF 81297. SKF 81297 at 2.5 and 5.0 mg/kg induced behavioural seizures. Electrophysiological recordings in the dentate gyrus revealed the presence of epileptiform discharges peaking at 30-45 min post-injection and declining by 60 min. Seizures were prevented by the D1-type receptor antagonist, SCH 23390, or the cannabinoid CB1 receptor agonist, CP 55,940. The effect of SKF 81297 was accompanied by increased phosphorylation of the extracellular signal-regulated protein kinases 1 and 2 (ERK), in the granule cells of the dentate gyrus. This effect was also observed in response to administration of other D1-type receptor agonists, such as SKF83822 and SKF83959. In addition, SKF 81297 increased the phosphorylation of the ribosomal protein S6 and histone H3, two downstream targets of ERK. These effects were prevented by genetic inactivation of D1Rs, or by pharmacological inhibition of ERK. SKF 81297 was also able to enhance the levels of Zif268 and Arc/Arg3.1, two immediate early genes involved in transcriptional regulation and synaptic plasticity. These changes may be involved in forms of activity-dependent plasticity linked to the manifestation of seizures and to the ability of dopamine to affect learning and memory.

Psychiatric disorders such as schizophrenia and autism are characterised by cellular disorganisation and dysconnectivity across the brain and can be caused by mutations in genes that control neurodevelopmental processes. To examine how neurodevelopmental defects can affect brain function and behaviour, we have comprehensively investigated the consequences of mutation of one such gene, Semaphorin-6A, on cellular organisation, axonal projection patterns, behaviour and physiology in mice. These analyses reveal a spectrum of widespread but subtle anatomical defects in Sema6A mutants, notably in limbic and cortical cellular organisation, lamination and connectivity. These mutants display concomitant alterations in the electroencephalogram and hyper-exploratory behaviour, which are characteristic of models of psychosis and reversible by the antipsychotic clozapine. They also show altered social interaction and deficits in object recognition and working memory. Mice with mutations in Sema6A or the interacting genes may thus represent a highly informative model for how neurodevelopmental defects can lead to anatomical dysconnectivity, resulting, either directly or through reactive mechanisms, in dysfunction at the level of neuronal networks with associated behavioural phenotypes of relevance to psychiatric disorders. The biological data presented here also make these genes plausible candidates to explain human linkage findings for schizophrenia and autism.

Hippocampal sclerosis is a common pathological finding in patients with temporal lobe epilepsy, including children, but a causal relationship to early-life seizures remains in question. Neonatal status epilepticus in animals can result in neuronal death within the hippocampus, although macroscopic features of hippocampal shrinkage are not evident at adulthood. Here, we examined electrophysiological and pathological consequences of focally evoked status epilepticus triggered by intra-amygdala microinjection of kainic acid in postnatal day 10 rat pups. Neonatal status epilepticus resulted in extensive neuronal death in the ipsilateral hippocampal CA1 and CA3 subfields and hilus, as assessed by DNA fragmentation and Fluoro-Jade B staining 72 hours later. The contralateral hippocampus was not significantly damaged. Histopathology at P55/P65 revealed unilateral hippocampal sclerosis (grade IV, modified Wyler/Watson scale) comprising >50% CA1 and CA3 neuron loss and astrogliosis. Additional features included hydrocephalus ex vacuo, modest dentate granule cell layer widening, and altered neuropeptide Y immunoreactivity indicative of synaptic rearrangement. Hippocampal atrophy was also evident on magnetic resonance imaging. Depth electrode recordings at adulthood detected spontaneous seizures that involved the ipsilateral hippocampus and amygdala. A significant positive correlation was found between hippocampal pathology grade and both frequency and duration of epileptic seizures at adulthood. The current study demonstrates that experimental neonatal status epilepticus can result in classical unilateral hippocampal sclerosis and temporal lobe epilepsy.

A novel bromide salt of the antidepressant bupropion (bupropion HBr) has recently been developed and approved for use in the United States. Given previous use of bromides to treat seizures, and that the existing chloride salt of bupropion (HCl) can cause seizures, it is important to determine if the HBr salt may be less likely to cause seizures than the HCl salt. In the present animal studies this was evaluated by means of quantified electroencephalogram (EEG), observation, and the rotarod test in mice and rats. Both bupropion salts were tested at increasing equimolar doses administered intraperitoneally. The results in mice showed that bupropion HCl 125 mg/kg induced a significantly higher ten-fold increase in the mean number of cortical EEG seizures compared to bupropion HBr (7.50 +/- 2.56 vs 0.75 +/- 0.96; p = 0.045), but neither drug caused any brain injuries. In rats bupropion HBr 100 mg/kg induced single EEG seizure activity in the cortical and hippocampal (depth) electrodes and in significantly (p < 0.05) fewer rats (44%) compared to bupropion HCl, which induced 1 to 4 convulsions per rat in all rats (100%) dosed. The total duration of cortical seizures in bupropion HCl-treated rats was significantly longer than the corresponding values obtained in bupropion HBr-treated rats (424.6 seconds vs 124.5 seconds respectively, p < 0.05). Bupropion HCl consistently induced more severe convulsions at each dose level compared to bupropion HBr. Both treatments demonstrated a similar dose-dependent impairment of rotarod performance in mice. In conclusion, these findings suggest that bupropion HBr may have a significantly lower potential to induce seizures in mice and rats, particularly at higher doses, compared to bupropion HCl. Determination of this potential clinical advantage will require human studies. If confirmed by such studies, it is likely that this potential beneficial clinical benefit would be due to the presence of the bromide salt given the long history of the use of bromide to treat seizure disorders.

Mesial temporal lobe epilepsy is the most common, intractable seizure disorder in adults. It is associated with an asymmetric pattern of hippocampal neuron loss within the endfolium (hilus and CA3) and CA1, with limited pathology in extra-hippocampal regions. We previously developed a model of focally-evoked seizure-induced neuronal death using intra-amygdala kainic acid (KA) microinjection and characterized the acute hippocampal pathology. Here, we sought to characterize the full extent of hippocampal and potential extra-hippocampal damage in this model, and the temporal onset of epileptic seizures. Seizure damage assessed at four stereotaxic levels by FluoroJade B staining was most prominent in ipsilateral hippocampal CA3 where it extended from septal to temporal pole. Minor but significant neuronal injury was present in ipsilateral CA1. Extra-hippocampal neuronal damage was generally limited in extent and restricted to the lateral septal nucleus, injected amygdala and select regions of neocortex ipsilateral to the seizure elicitation side. Continuous surface EEG recorded with implanted telemetry units in freely-moving mice detected spontaneous, epileptic seizures by five days post-KA in all mice. Epileptic seizure number averaged 1-4 per day. Hippocampi from epileptic mice 15 days post-KA displayed unilateral CA3 lesions, astrogliosis and increased neuropeptide Y immunoreactivity suggestive of mossy fiber rearrangement. These studies characterize a mouse model of unilateral hippocampal-dominant neuronal damage and short latency epileptogenesis that may be suitable for studying the cell and molecular pathogenesis of human mesial temporal lobe epilepsy.