Heat stress associated with aerosol PPE and its impact.

BACKGROUND: Aerosol personal protective equipment (PPE) is subjectively reported to negatively impact healthcare workers' performance and well-being, but this has not been assessed objectively. AIMS: This randomized controlled crossover study aimed to quantify the heat stress associated with aerosol PPE and to investigate its impact upon mood, cognitive and motor function, and task performance. METHODS: Sixteen healthy, young, lean participants (eight males) undertook an exercise protocol, which simulated the metabolic expenditure of hospital work: once wearing aerosol PPE (PPE visit) and once wearing standard surgical attire (control visit). Participants walked on a treadmill for 2 h followed by 30-min rest. Core temperature, heart rate, urine specific gravity, weight, grip strength, mood (Bond-Lader scale) and task performance (Intubation of a Manikin) were recorded. Values are between-visit mean (standard deviation) differences. RESULTS: On the PPE visit core temperature (+0.2 (0.3)°C; P < 0.01), heart rate (+12 (13) bpm; P < 0.001), urine specific gravity (+0.003 (0.005); P < 0.05) and intubation task time (+50 (81) s; P < 0.01) were greater than on the control visit; and alertness (-14 (21) mm; P < 0.001), contentment (-14 (15) mm; P < 0.001) and grip strength (-4 (4) N; P < 0.01) were less. CONCLUSIONS: This study demonstrates that wearing aerosol PPE in a simulated hospital environment results in heat exhaustion and has a negative impact upon mood, motor function, and task performance. Whilst wearing PPE is important to prevent disease transmission, strategies should be developed to limit its impact upon healthcare workers' performance and well-being.

Importance of cannulated prolactin test in the definition of hyperprolactinaemia.

PURPOSE: Recent guidelines suggest that a single prolactin measurement is adequate to confirm hyperprolactinaemia. This may lead to unnecessary investigation of artefactual hyperprolactinaemia. Prolactin measurement drawn from an indwelling cannula after rest removes stress as a confounding variable. The objective was to determine the frequency of true hyperprolactinaemia amongst patients referred following a single prolactin measurement. METHODS: A cannulated study was considered if prolactin on referral ('Referral Prolactin') was <5,500 mU/L (260 ng/mL) but >410 mU/L (19 ng/mL) in males or >510 mU/L (24 ng/mL) in females, irrespective of clinical context. Case-notes of 267 patients undergoing cannulated prolactin measurement over a 10-year period (2000-2010) were reviewed. Pre-existing pituitary disease, dopamine antagonist use, and macroprolactinaemia were excluded. Morning ante-cubital vein cannulation was followed immediately by withdrawal of 'Repeat Prolactin' sample. After 120-min bed-rest, 'Resting Prolactin' was withdrawn through the cannula. RESULTS: 235 patients were included for analysis. 64 (27%) were within normal range; following Repeat Prolactin in 41 (17%) and Resting Prolactin in 23 (9%) cases. Referral Prolactin was higher in patients with true hyperprolactinaemia, 1,637 ± 100 mU/L (77.2 ± 4.7 ng/mL) than with artefactual hyperprolactinaemia, 1,122 ± 68 mU/L (52.9 ± 3.2 ng/mL; P < 0.001) but there was substantial overlap. 21 out of 171 cases (12%) with true hyperprolactinaemia had a macroadenoma. Presenting symptoms did not predict true hyperprolactinaemia. Referral Prolactin of 2,000 mU/L (94 ng/mL) had 97% specificity to identify true hyperprolactinaemia. CONCLUSIONS: Reliance on a single, non-rested prolactin value may lead to over-diagnosis of hyperprolactinaemia. A resting sample should be considered with random values <2,000 mU/L (94 ng/mL).

Biomechanical determinants of elite rowing technique and performance.

In rowing, the parameters of injury, performance, and technique are all interrelated and in dynamic equilibrium. Whilst rowing requires extreme physical strength and endurance, a high level of skill and technique is essential to enable an effective transfer of power through the rowing sequence. This study aimed to determine discrete aspects of rowing technique, which strongly influence foot force production and asymmetries at the foot-stretchers, as these are biomechanical parameters often associated with performance and injury risk. Twenty elite female rowers performed an incremental rowing test on an instrumented rowing ergometer, which measured force at the handle and foot-stretchers, while three-dimensional kinematic recordings of the ankle, knee, hip, and lumbar-pelvic joints were made. Multiple regression analyses identified hip kinematics as a key predictor of foot force output (R(2) = 0.48), whereas knee and lumbar-pelvic kinematics were the main determinants in optimizing the horizontal foot force component (R(2) = .41). Bilateral asymmetries of the foot-stretchers were also seen to significantly influence lumbar-pelvic kinematics (R(2) = 0.43) and pelvic twisting (R(2) = 0.32) during the rowing stroke. These results provide biomechanical evidence toward aspects of technique that can be modified to optimize force output and performance, which can be of direct benefit to coaches and athletes.

Phaeochromocytoma [corrected] crisis.

Phaeochromocytoma [corrected] crisis is an endocrine emergency associated with significant mortality. There is little published guidance on the management of phaeochromocytoma [corrected] crisis. This clinical practice update summarizes the relevant published literature, including a detailed review of cases published in the past 5 years, and a proposed classification system. We review the recommended management of phaeochromocytoma [corrected] crisis including the use of alpha-blockade, which is strongly associated with survival of a crisis. Mechanical circulatory supportive therapy (including intra-aortic balloon pump or extra-corporeal membrane oxygenation) is strongly recommended for patients with sustained hypotension. Surgical intervention should be deferred until medical stabilization is achieved.

When is an outbreak not an outbreak? Fit, divergent strains of Mycobacterium tuberculosis display independent evolution of drug resistance in a large London outbreak.

OBJECTIVES: To study the evolutionary relationship of Mycobacterium tuberculosis isolates from 13 patients in a large outbreak of isoniazid-resistant tuberculosis in London. METHODS: Genotypic and phenotypic susceptibility tests were performed. Molecular genotyping using restriction fragment length polymorphisms and mycobacterial interspersed repetitive units was carried out. Additionally, the generation times of 13 strains of M. tuberculosis from the outbreak were measured to determine relative fitness. RESULTS: Genotypic and phenotypic susceptibility testing demonstrated variations between isolates. Polymorphisms causing isoniazid resistance varied within clusters of isolates that were indistinguishable by standard genotyping. The measurement of in vitro generation times demonstrated that the fitness of the resistant strains was not significantly different from either wild-type or susceptible isolates in the outbreak, indicating that apparently no fitness cost was associated with the acquisition of drug resistance. CONCLUSIONS: It appears that this outbreak comprised a heterogeneous collection of closely related strains, which appear to exhibit more variation than would usually be associated with a point source outbreak. These strains appear to have evolved by acquisition of additional antimicrobial resistance mutations while remaining competitive. The acquired resistance and retained competitiveness may be partly responsible for the difficulty in controlling the outbreak.

Diabetes mellitus is not a predictor of poor TB treatment outcomes.

OBJECTIVE: To investigate whether diabetes mellitus (DM) influences TB treatment outcomes.METHODS: This was a retrospective observational cohort study of all notified TB cases from a large London TB centre over a 5-year period. WHO criteria were used to define TB treatment outcomes.RESULTS: The prevalence of DM at TB treatment initiation was 15% (126/838). Most patients (83.3%, 105/126) were on hypoglycaemic treatment and well-controlled (median glycated haemoglobin 53.5 mmol/mol). DM patients were older, more likely to be of Asian ethnicity and had a higher pre-treatment weight. Time from presentation to treatment initiation was longer (median 87.5 vs. 63 days; P < 0.001), while they were significantly more comorbid (median Charlson Comorbidity Index 3 vs. 0; P < 0.001). Overall, favourable treatment outcomes were recorded for 89.5% of patients (87.7% vs. 89.8% for DM and non-DM patients respectively, P = 0.52). In multivariable analysis, DM was not associated with unfavourable TB treatment outcomes (OR 0.49, 95% CI 0.23-1.04, P = 0.06). Independent predictors of unfavourable outcome included age, cavitation, chronic neurological disease and malignant neoplasm.CONCLUSIONS: In a well-resourced setting, with predominantly well-controlled DM patients on treatment, DM was not an independent predictor of unfavourable TB treatment outcomes.

Helicobacter pylori infection assessed by ELISA and by immunoblot and noncardia gastric cancer risk in a prospective study: the Eurgast-EPIC project.

BACKGROUND: In epidemiological studies, Helicobacter pylori infection is usually detected by enzyme-linked immunosorbent assay (ELISA). However, infection can spontaneously clear from the mucosa during the progression of atrophy and could lead to substantial under-detection of infection and underestimation of its effect on gastric cancer (GC) risk. Antibodies detected by western blot are known to persist longer after the loss of the infection. METHODS: In a nested case-control study from the Eurogast-EPIC cohort, including 88 noncardia GC cases and 338 controls, we assessed the association between noncardia GC and H. pylori infection comparing antibodies detected by western blot (HELICOBLOT2.1) to those detected by ELISA (Pyloriset EIA-GIII(®)). RESULTS: By immunoblot, 82 cases (93.2%) were H. pylori positive, 10 of these cases (11.4%) were negative by ELISA and only 6 cases (6.8%) were negative by both ELISA and immunoblot. Multivariable odds ratio (OR) for noncardia GC comparing immunoglobulin G positive versus negative by ELISA was 6.8 [95% confidence interval (CI) 3.0-15.1], and by immunoblot, the OR was 21.4 (95% CI 7.1-64.4). CONCLUSIONS: Using a western blot assay, nearly all noncardia GC were classified as H. pylori positive and the OR was more than threefold higher than the OR assessed by ELISA, supporting the hypothesis that H. pylori infection is a necessary condition for noncardia GC.

Effect of primary percutaneous coronary intervention on stress hyperglycaemia in myocardial infarction.

AIM: To measure the effect of primary percutaneous coronary intervention on stress hyperglycaemia induced by ST segment elevation myocardial infarction. METHODS: We measured blood glucose before primary percutaneous coronary intervention and 1 h after intervention in all patients presenting with ST segment elevation myocardial infarction for 2 months in our unit. A paired t-test was used for a statistical analysis. RESULTS: From 157 patients accepted for primary percutaneous coronary intervention, 90 patients were included in the analysis. Blood glucose before intervention was 8.4 ± 2.46 mmol/l (mean ± SD) and after intervention was 7.9 ± 2.0 mmol/l (mean ± sd) (P = 0.003). In the subset of 15 patients with hyperglycaemia (glucose greater than 10 mmol/l), glucose before intervention was 12.7 ± 2.62 mmol/l (mean ± SD) and after intervention was 9.8 ± 3.42 mmol/l (mean ± sd) (P = 0.0002). CONCLUSIONS: Blood glucose in patients with ST segment elevation myocardial infarction is significantly lower after primary percutaneous coronary intervention and this reduction is most marked in patients with hyperglycaemia. Waiting for the stress response to diminish means that 11.1% of patients' glucose levels fell below the treatment threshold of 10 mmol/l. Using the post-intervention blood glucose level avoids the need for treatment with insulin in this population. Further randomized studies are warranted to investigate the impact on mortality and morbidity of administering insulin triggered by pre-invention blood glucose vs. post-intervention blood glucose.

Response of glutathione S-transferase Pi (GSTP1) to neoadjuvant therapy in rectal adenocarcinoma.

AIM: The response of rectal adenocarcinoma to neoadjuvant therapy is variable. Accurate prediction of response would enable selective administration of therapy. The enzyme glutathione S-transferase Pi (GSTP1) has been shown to influence response to therapy in some solid tumours. Few data are available for rectal cancer. METHOD: The GSTP1 levels in rectal adenocarcinoma and adjacent normal mucosa were quantified before and after exposure to neoadjuvant therapy. Venous blood samples and biopsies of normal rectal mucosa and tumour were prospectively obtained from patients with primary rectal cancer. Patients were stratified by exposure to neoadjuvant therapy or surgery alone. GSTP1 was quantitatively measured using an enzyme-linked immunosorbent assay. RESULTS: Ninety-two patients (54 men; median age 68 years) were recruited. The median GSTP1 level was significantly higher in rectal adenocarcinoma than in matched normal mucosa [6.59 µg/mg vs 4.57 µg/mg; P < 0.001]. The median tumour GSTP1 level was significantly lower in the therapy group compared with unmatched samples from the no-therapy group [4.47 µg/mg vs 7.76 µg/mg; P < 0.001]. CONCLUSION: The GSTP1 level is increased in rectal adenocarcinoma compared with adjacent normal mucosa. It decreases following neoadjuvant therapy. Future studies correlating pre-therapy GSTP1 levels with pathological response would be of interest.

Patients' views on an education booklet following spinal surgery.

PURPOSE: This study evaluated an evidence-based education booklet developed for patients undergoing spinal surgery which was used as a treatment intervention in a multi-centre, factorial, randomised controlled trial (FASTER: Function after spinal treatment, exercise and rehabilitation) investigating the post-operative management of spinal surgery patients. This study sought to determine the acceptability and content of the booklet to patients. METHODS: Patients receiving the educational booklet before discharge from hospital as part of the FASTER study were asked to complete an evaluation, which rated the booklet "Your Back Operation" with regard to content, information, usability, etc. using forced and open questions. This assessment was conducted at the same time as the initial 6-week post-operative review performed as part of the larger study. RESULTS: Therefore, 97% of the 117 trial participants who returned their 6-week evaluation and randomised to receive a booklet returned their questionnaire. The booklet was highly rated receiving an overall rating of 7 or more out of 10 from 101/111 (91%), and high ratings for content, readability and information. The booklet's key messages were clear to the majority of patients; however, many patients highlighted deficiencies with respect to content particularly in relation to wound care and exercise. CONCLUSIONS: Patients valued the booklet and rated its content highly. Many suggested that the booklet be developed further and there was a clear desire for specific exercises to be included even though there is no evidence to support specific exercise prescription.

Chondrocyte repopulation of the zone of death induced by osteochondral harvest.

OBJECTIVE: Harvesting osteochondral grafts results in a zone of chondrocyte death (ZCD) in and around the periphery of the graft, creating a barrier for chondrocytes to migrate to the graft periphery, thus limiting cartilage-to-cartilage healing. The purpose of this study was to repopulate the induced ZCD through the combined effects of collagenase treatment and delivery of a chemotactic agent. DESIGN: In bovine cartilage, the ZCD induced by the OATS™ osteochondral harvesting system was determined, followed by a corresponding collagenase treatment to penetrate the developed ZCD. The chemotactic potential of platelet derived growth factor (PDGF-bb), insulin-like growth factor I (IGF-I), and basic fibroblast growth factor (bFGF) (2.5-100 ng/mL) was then assessed using a modified Boyden chamber assay to select an appropriate agent to induce chondrocyte migration. Afterwards, the combined effects of collagenase treatment and chondrocyte chemotaxis on the repopulation of an induced ZCD were examined in cartilage explants over a 4-week-period. RESULTS: The OATS™ osteochondral harvesting system induced a significant ZCD (173 µm, 95% CI: [72-274 µm]) in the grafts. Chondrocyte chemotaxis was induced by all agents investigated at concentrations greater than 25 ng/mL. After 4 weeks in culture, collagenase treatment alone reduced the ZCD by approximately 40% relative to untreated explants. Coupling the collagenase treatment with 25 ng/mL IGF-I reduced the ZCD by approximately 80% relative to untreated explants, and 65% relative to explants treated only with collagenase. CONCLUSION: Treating cartilage explants with collagenase and 25 ng/mL IGF-I resulted in a decreased ZCD after a 4-week-period, and increased chondrocyte density within the induced ZCD.

Predicting the lumbosacral joint centre location from palpable anatomical landmarks.

The kinematics of the lumbar spine have previously been described by considering the bearing of the pelvis and lower back. However earlier studies have not described an intersegmental angle measured about a single point; which is necessary for investigation into movement, posture and balance, and lower back pain and injury. This study used computed tomography (CT) scans of 16 pelves to determine the location of palpable bony landmarks, and the junction of the fifth lumbar and first sacral vertebrae within a pelvis axis system. Data were used to derive equations which express the three-dimensional location of the lumbosacral joint centre as an offset from palpable surface landmarks. The magnitude of X, Y, Z offsets was controlled using individual pelvic geometry, and robustness and repeatability of the method was assessed. Regression equations provided the location of the lumbosacral junction to within 8.2mm (+/- 3.4mm) of its true coordinate. Leave-one-out analyses calculated equation coefficients using 15 of the original pelves, with the 16th acting as a control; average errors increased by 6.7 per cent (+/- 0.1 percent). To the authors' knowledge the current method is the most accurate non-invasive means of locating the lumbosacral junction and may be useful for constructing biomechanical models.

An open-source musculoskeletal model of the lumbar spine and lower limbs: a validation for movements of the lumbar spine.

Musculoskeletal models of the lumbar spine have been developed with varying levels of detail for a wide range of clinical applications. Providing consistency is ensured throughout the modelling approach, these models can be combined with other computational models and be used in predictive modelling studies to investigate bone health deterioration and the associated fracture risk. To provide precise physiological loading conditions for such predictive modelling studies, a new full-body musculoskeletal model including a detailed and consistent representation of the lower limbs and the lumbar spine was developed. The model was assessed against in vivo measurements from the literature for a range of spine movements representative of daily living activities. Comparison between model estimations and electromyography recordings was also made for a range of lifting tasks. This new musculoskeletal model will provide a comprehensive physiological mechanical environment for future predictive finite element modelling studies on bone structural adaptation. It is freely available on https://simtk.org/projects/llsm/.

Comprehensive survey of developmental genes in the pea aphid, Acyrthosiphon pisum: frequent lineage-specific duplications and losses of developmental genes.

Aphids exhibit unique attributes, such as polyphenisms and specialized cells to house endosymbionts, that make them an interesting system for studies at the interface of ecology, evolution and development. Here we present a comprehensive characterization of the developmental genes in the pea aphid, Acyrthosiphon pisum, and compare our results to other sequenced insects. We investigated genes involved in fundamental developmental processes such as establishment of the body plan and organogenesis, focusing on transcription factors and components of signalling pathways. We found that most developmental genes were well conserved in the pea aphid, although many lineage-specific gene duplications and gene losses have occurred in several gene families. In particular, genetic components of transforming growth factor beta (TGFbeta) Wnt, JAK/STAT (Janus kinase/signal transducer and activator of transcription) and EGF (Epidermal Growth Factor) pathways appear to have been significantly modified in the pea aphid.

Function after spinal treatment, exercise and rehabilitation (FASTER): improving the functional outcome of spinal surgery.

BACKGROUND: The life-time incidence of low back pain is high and diagnoses of spinal stenosis and disc prolapse are increasing. Consequently, there is a steady rise in surgical interventions for these conditions. Current evidence suggests that while the success of surgery is incomplete, it is superior to conservative interventions. A recent survey indicates that there are large differences in the type and intensity of rehabilitation, if any, provided after spinal surgery as well as in the restrictions and advice given to patients in the post-operative period. This trial will test the hypothesis that functional outcome following two common spinal operations can be improved by a programme of post-operative rehabilitation that combines professional support and advice with graded active exercise and/or an educational booklet based on evidence-based messages and advice. METHODS/DESIGN: The study design is a multi-centre, factorial, randomised controlled trial with patients stratified by surgeon and operative procedure. The trial will compare the effectiveness and cost-effectiveness of a rehabilitation programme and an education booklet for the postoperative management of patients undergoing discectomy or lateral nerve root decompression, each compared with "usual care"using a 2 x 2 factorial design. The trial will create 4 sub-groups; rehabilitation-only, booklet-only, rehabilitation-plus-booklet, and usual care only. The trial aims to recruit 344 patients, which equates to 86 patients in each of the four sub-groups. All patients will be assessed for functional ability (through the Oswestry Disability Index - a disease specific functional questionnaire), pain (using visual analogue scales), and satisfaction pre-operatively and then at 6 weeks, 3, 6 and 9 months and 1 year post-operatively. This will be complemented by a formal analysis of cost-effectiveness. DISCUSSION: This trial will determine whether the outcome of spinal surgery can be enhanced by either a post-operative rehabilitation programme or an evidence-based advice booklet or a combination of the two and as such will contribute to our knowledge on how to manage spinal surgery patients in the post-operative period.

Reliability and minimal detectable change of the 'Imperial Spine' marker set for the evaluation of spinal and lower limb kinematics in adults.

OBJECTIVES: As a step towards the comprehensive evaluation of movement in patients with low back pain, the aim of this study is to design a marker set (three rigid segment spine, pelvic and lower limb model) and evaluate the reliability and minimal detectable change (MDC) of this marker set in healthy adults during gait and sit to stand (STS) tasks using three dimensional motion capture. RESULTS: The 'Imperial Spine' marker set was used to assess relative peak angles during gait and STS tasks using the minimum recommended sample size (n = 10) for reliability studies with minimum Intraclass Correlation Coefficient (ICC) of 0.70, optimum ICC 0.90 and 9 trials replicated per subject per task. Intra- and inter-tester reliability between an experienced and inexperienced user was examined. ICC, mean, standard error (SEM), Bland Altman 95% limits of agreement (LOA) and MDC were computed. ICC values demonstrated excellent intra- and inter-tester reliability in both tasks, particularly in the sagittal plane (majority ICCs > 0.80). SEM measurements were lower in gait (0.8-5.5°) than STS tasks (1°-12.6°) as were MDC values. LOA demonstrated good agreement. The 'Imperial Spine' marker set is reliable for use in healthy adults during functional tasks. Future evaluation in patients is required.

Nucleophosmin is a novel Bax chaperone that regulates apoptotic cell death.

The proapoptotic B-cell lymphoma-2 family protein Bax is a key regulatory point in the intrinsic apoptotic pathway. However, the factors controlling the process of Bax activation and translocation to mitochondria have yet to be fully identified and characterized. We performed affinity chromatography using peptides corresponding to the mitochondrial-targeting region of Bax, which is normally sequestered within the inactive structure. The molecular chaperone nucleophosmin was identified as a novel Bax-binding protein by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Reciprocal co-immunoprecipitation and proximity assays confirmed the Bax-nucleophosmin protein-protein interaction and verified that nucleophosmin only bound to activated conformationally altered Bax. Confocal microscopy in a cell-based apoptosis model, demonstrated that nucleophosmin translocation from nucleolus to cytosol preceded Bax movement. Specific knockdown of nucleophosmin expression using RNAi attenuated apoptosis as measured by mitochondrial cytochrome c release and activation of the caspase cascade. In a mouse model of ischaemic stroke, subcellular fractionation studies verified that nucleophosmin translocation occurred within 3 h, at a time before Bax translocation but after Bax conformational changes have occurred. Thus, we have elucidated a novel molecular mechanism whereby Bax becomes activated and translocates to the mitochondria to orchestrate mitochondrial dysfunction and apoptotic cell death, which opens new avenues for therapeutic intervention.

Autoimmune thyroid disease: further developments in our understanding.

The revolution in molecular techniques has allowed dissection of the autoimmune response in a way impossible to imagine 10 yr ago. There have been spectacular advances in our understanding of self-tolerance mechanisms and how these may fail, combined with a detailed comprehension of antigen presentation, functional T cell subsets, and TCR utilization in autoimmunity, albeit usually in animal models that resemble, but do not exactly duplicate, human diseases. More gradually, these findings are being translated to thyroid autoimmunity, where the major achievement of the last decade has been the molecular characterization of the three main thyroid autoantigens. This in turn has allowed epitope identification, although again the only clear data so far have come from animal models of EAT. Another advance has been the recognition that the thyrocyte is not a helpless target of autoaggression, being capable of expressing a wide array of immunologically active molecules, which may exacerbate or diminish the autoimmune response. In 1983, there was considerable excitement at the discovery of the first of these phenomena, namely MHC class II expression, but its possible role in autoantigen presentation remains to be defined. By analogy with pancreatic beta-cells, and based on our own data, we believe that class II-expressing thyrocytes have little, if any, such role and suspect that instead this may be a mechanism for inducing peripheral tolerance. Defining the contribution of thyrocytes to the intrathyroidal autoimmune response, whether from released cytokines or surface-bound molecules, will be crucial to our future understanding, as well as holding the promise that these thyroid-derived products might be therapeutic targets. Despite molecular developments in HLA analysis, there have been no really major improvements in our understanding of the immunogenetics of thyroid autoimmunity, equivalent to those made in type 1 diabetes mellitus. The available data suggest strongly that non-MHC genes play an important role in susceptibility, and novel approaches will be required to identify these. On the other hand, we know more about the importance of environmental and endogenous (most probably hormonal) factors in thyroid autoimmunity. Understanding the basic immunological changes in the postpartum period is still poor, however, as most studies to date have concentrated on epidemiology and clinical delineation. As PPTD undergoes spontaneous remission, elucidation of these mechanisms has clear implications for treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Temporal profile of subventricular zone progenitor cell migration following quinolinic acid-induced striatal cell loss.

A number of studies have demonstrated directed migration of neural progenitor cells to sites of brain injury and disease, however a detailed examination of when a cell is "born" in relation to injury induction and the migratory response of that cell has not previously been determined. This study therefore examined the temporal correlation between progenitor cell proliferation ("birth") and neuroblast migratory response into the damaged striatum following quinolinic acid (QA) lesioning of the adult rat striatum. Retroviral labeling of subventricular zone (SVZ)-derived progenitor cells demonstrated that cell loss in the QA-lesioned striatum increased progenitor cell migration through the rostral migratory stream (RMS) for up to 30 days. In addition, a population of dividing cells originating from the SVZ generated doublecortin positive neuroblasts that migrated into the damaged striatum in response to cell loss invoked by the QA lesion. Quantification of bromodeoxyuridine (BrdU)-labeled cells co-expressing doublecortin revealed that the majority of cells present in the damaged striatum were generated from progenitor cells dividing within 2 days either prior to or following the QA lesion. In contrast, cells dividing 2 or more days following QA lesioning, migrated into the striatum and exhibited a glial phenotype. These results demonstrate that directed migration of SVZ-derived cells and neuroblast differentiation in response to QA lesioning of the striatum is acute and transient. We propose this is predominantly due to a reduced capacity over time for newly generated neuroblasts to respond to the lesioned environment due to a loss or inhibition of migratory cues.