Browsing by Subject "BRAIN-INJURY"

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  • Heikkilä, Helka M.; Jokinen, Tarja S.; Syrjä, Pernilla; Junnila, Jouni; Hielm-Björkman, Anna; Laitinen-Vapaavuori, Outi (2018)
    Objective To investigate the clinical, cytological, and histopathological adverse effects of intra-articularly injected botulinum toxin A in dogs and to study whether the toxin spreads from the joint after the injection. Methods A longitudinal, placebo-controlled, randomized clinical trial was conducted with six healthy laboratory Beagle dogs. Stifle joints were randomized to receive either 30 IU of onabotulinum toxin A or placebo in a 1: 1 ratio. Adverse effects and spread of the toxin were examined by evaluating dynamic and static weight-bearing of the injected limbs, by assessing painless range of motion and pain on palpation of joints, and by performing synovial fluid analysis, neurological examination, and electrophysiological recordings at different examination timepoints in a 12-week period after the injections. The dogs were then euthanized and autopsy and histopathological examination of joint structures and adjacent muscles and nerves were performed. Results Intra-articular botulinum toxin A did not cause local weakness or injection site pain. Instead, static weight-bearing and painless range of motion of stifle joints decreased in the placebo limbs. No clinically significant abnormalities associated with intra-articular botulinum toxin A were detected in the neurological examinations. Electrophysiological recordings showed low compound muscle action potentials in two dogs in the botulinum toxin A-injected limb. No significant changes were detected in the synovial fluid. Autopsy and histopathological examination of the joint and adjacent muscles and nerves did not reveal histopathological adverse effects of the toxin. Conclusion Intra-articular botulinum toxin A does not produce significant clinical, cytological, or histopathological adverse effects in healthy dogs. Based on the electrophysiological recordings, the toxin may spread from the joint, but its clinical impact seems to be low.
  • Haywood, Kirstie L.; Pearson, Nathan; Morrison, Laurie J.; Castren, Maaret; Lilja, Gisela; Perkins, Gavin D. (2018)
    Aim: High quality evidence of out-of-hospital cardiac arrest (OHCA) survivors' health-related quality of life (HRQoL) can measure the long-term impact of CA. The aim of this study was to critically appraise the evidence of psychometric quality and acceptability of measures used in the assessment of HRQoL in cardiac arrest survivors. Methods: Systematic literature searches (2004-2017) and named author searches to identify articles pertaining to the measurement of HRQoL. Data on study quality, measurement and practical properties were extracted and assessed against international standards. Results: From 356 reviewed abstracts, 69 articles were assessed in full. 25 provided evidence for 10 measures of HRQoL: one condition-specific; three generic profile measures; two generic index; and four utility measures. Although limited, evidence for measurement validity was strongest for the HUI3 and SF-36. However, evidence for reliability, content validity, responsiveness and interpretability and acceptability was generally limited or not available in the CA population for all measures. Conclusions: This review has demonstrated that a measure of quality of life specific to OHCA survivors is not available. Limited evidence of validity exists for one utility measure - the HUI3 - and a generic profile - the SF-36. Robust evidence of the quality and acceptability of HRQoL measures in OHCA was limited or not available. Future collaborative research must seek to urgently establish the relevance and acceptability of these measures to OHCA survivors, to establish robust evidence of essential measurement and practical properties over the short and long-term, and to inform future HRQoL assessment in the OHCA population. (C) 2017 Elsevier B.V. All rights reserved.
  • Aneman, Anders; Laurikalla, Johanna; Pham, Paul; Wilkman, Erika; Jakkula, Pekka; Reinikainen, Matti; Toppila, Jussi; Skrifvars, Markus B. (2019)
    Background Approximately two-thirds of the mortality following out of hospital cardiac arrest is related to devastating neurological injury. Previous small cohort studies have reported an impaired cerebrovascular autoregulation following cardiac arrest, but no studies have assessed the impact of differences in oxygen and carbon dioxide tensions in addition to mean arterial pressure management. Methods This is a protocol and statistical analysis plan to assess the correlation between changes in cerebral tissue oxygenation and arterial pressure as measure of cerebrovascular autoregulation, the tissue oxygenation index, in patients following out of hospital cardiac arrest and in healthy volunteers. The COMACARE study included 120 comatose survivors of out of hospital cardiac arrest admitted to ICU and managed with low-normal or high-normal targets for mean arterial pressure, arterial oxygen and carbon dioxide partial pressures. In addition, 102 healthy volunteers have been investigated as a reference group for the tissue oxygenation index. In both cohorts, the cerebral tissue oxygenation was measured by near infrared spectroscopy. Conclusions Cerebrovascular autoregulation is critical to maintain homoeostatic brain perfusion. This study of changes in autoregulation following out of hospital cardiac arrest over the first 48 hours, as compared to data from healthy volunteers, will generate important physiological information that may guide the rationale and design of interventional studies.
  • Leikos, Susanna; Tokariev, Anton; Koolen, Ninah; Nevalainen, Päivi; Vanhatalo, Sampsa (2020)
    Abstract The conventional assessment of preterm somatosensory functions using averaged cortical responses to electrical stimulation ignores the characteristic components of preterm somatosensory evoked responses (SERs). Our study aimed to systematically evaluate the occurrence and development of SERs after tactile stimulus in preterm infants. We analysed SERs performed during 45 electroencephalograms (EEGs) from 29 infants at the mean post-menstrual age of 30.7 weeks. Altogether 2,087 SERs were identified visually at single trial level from unfiltered signals capturing also their slowest components. We observed salient SERs with a high amplitude slow component at a high success rate after hand (95%) and foot (83%) stimuli. There was a clear developmental change in both the slow wave and the higher frequency components of the SERs. Infants with intraventricular haemorrhage (IVH; eleven infants) had initially normal SERs, but those with bilateral IVH later showed a developmental decrease in the ipsilateral SER occurrence after 30 weeks of post-menstrual age. Our study shows that tactile stimulus applied at bedside elicits salient SERs with a large slow component and an overriding fast oscillation, which are specific to the preterm period. Prior experimental research indicates that such SERs allow studying both subplate and cortical functions. Our present findings further suggest that they might offer a window to the emergence of neurodevelopmental sequalae after major structural brain lesions and, hence, an additional tool for both research and clinical neurophysiological evaluation of infants before term age.
  • Airaksinen, Noora K.; Nurmi-Lüthje, Ilona S.; Kataja, J. Matti; Kröger, Heikki P. J.; Lüthje, Peter M. J. (2018)
    Background: Most of the cycling accidents that occur in Finland do not end up in the official traffic accident statistics. Thus, there is minimal information on these accidents and their consequences, particularly in cases in which alcohol was involved. The focus of the present study is on cycling accidents and injuries involving alcohol in particular. Methods: Data on patients visiting the emergency department at North Kymi Hospital because of a cycling accident was prospectively collected for two years, from June 1, 2004 to May 31, 2006. Blood alcohol concentration (BAC) was measured on admission with a breath analyser. The severity of the cycling injuries was classified according to the Abbreviated Injury Scale (AIS). Results: A total of 217 cycling accidents occurred. One third of the injured cyclists were involved with alcohol at the time of visiting the hospital. Of these, 85% were males. A blood alcohol concentration of Conclusions: Cyclists involved with alcohol were, in most cases, heavily intoxicated and were not wearing a bicycle helmet. Head injuries were more common among these cyclists than among sober cyclists. As cycling continues to increase, it is important to monitor cycling accidents, improve the accident statistics and heighten awareness of the risks of head injuries when cycling under the influence of alcohol. (c) 2018 Elsevier Ltd. All rights reserved.
  • Nevalainen, Päivi; Marchi, Viviana; Metsäranta, Marjo; Lönnqvist, Tuula; Toiviainen-Salo, Sanna; Vanhatalo, Sampsa; Lauronen, Leena (2017)
    Objective: To evaluate the added value of somatosensory (SEPs) and visual evoked potentials (VEPs) recorded simultaneously with routine EEG in early outcome prediction of newborns with hypoxicischemic encephalopathy under modern intensive care. Methods: We simultaneously recorded multichannel EEG, median nerve SEPs, and flash VEPs during the first few postnatal days in 50 term newborns with hypoxic-ischemic encephalopathy. EEG background was scored into five grades and the worst two grades were considered to indicate poor cerebral recovery. Evoked potentials were classified as absent or present. Clinical outcome was determined from the medical records at a median age of 21 months. Unfavorable outcome included cerebral palsy, severe mental retardation, severe epilepsy, or death. Results: The accuracy of outcome prediction was 98% with SEPs compared to 90% with EEG. EEG alone always predicted unfavorable outcome when it was inactive (n = 9), and favorable outcome when it was normal or only mildly abnormal (n = 17). However, newborns with moderate or severe EEG background abnormality could have either favorable or unfavorable outcome, which was correctly predicted by SEP in all but one newborn (accuracy in this subgroup 96%). Absent VEPs were always associated with an inactive EEG, and an unfavorable outcome. However, presence of VEPs did not guarantee a favorable outcome. Conclusions: SEPs accurately predict clinical outcomes in newborns with hypoxic-ischemic encephalopathy and improve the EEG-based prediction particularly in those newborns with severely or moderately abnormal EEG findings. Significance: SEPs should be added to routine EEG recordings for early bedside assessment of newborns with hypoxic-ischemic encephalopathy. (C) 2017 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
  • Sun, Weilun; Suzuki, Kunimichi; Toptunov, Dmytro; Stoyanov, Stoyan; Yuzaki, Michisuke; Khiroug, Leonard; Dilyatev, Alexander (2019)
    Two-photon imaging of fluorescently labeled microglia in vivo provides a direct approach to measure motility of microglial processes as a readout of microglial function that is crucial in the context of neurodegenerative diseases, as well as to understand the neuroinflammatory response to implanted substrates and brain-computer interfaces. In this longitudinal study, we quantified surveilling and photodamage-directed microglial processes motility in both acute and chronic cranial window preparations and compared the motility under isoflurane and ketamine anesthesia to an awake condition in the same animal. The isoflurane anesthesia increased the length of surveilling microglial processes in both acute and chronic preparations, while ketamine increased the number of microglial branches in acute preparation only. In chronic (but not acute) preparation, the extension of microglial processes toward the laser-ablated microglial cell was faster under isoflurane (but not ketamine) anesthesia than in awake mice, indicating distinct effects of anesthetics and of preparation type. These data reveal potentiating effects of isoflurane on microglial response to damage, and provide a framework for comparison and optimal selection of experimental conditions for quantitative analysis of microglial function using two-photon microscopy in vivo.
  • Skrifvars, Markus B.; Aneman, Anders; Ameloot, Koen (2020)
    Purpose of review To discuss recent findings relevant to optimizing blood pressure targets in adult, postcardiac arrest (PCA) patients and whether to tailor these based on specific patient, cardiac arrest or treatment characteristics. Recent findings Observational data suggest that mean arterial pressure (MAP) below 65-75 mmHg in PCA patients is associated with worse outcome. A higher MAP could be beneficial in patients with chronic hypertension who more frequently have a right shift of the cerebral autoregulation curve. Two recent randomized pilot trials compared lower and higher MAP targets during PCA care and found no significant effect on biomarkers of neurological injury. The haemodynamic interventions in those studies did not use any cerebral perfusion endpoints beyond a static MAP targets during ICU stay. Individualized, dynamic MAP targets based on assessments of cerebral perfusion and tailored to the specifics of the patient, cardiac arrest circumstances and treatment responses may be more conducive to improved outcomes. Pilot data suggest that near infrared spectroscopy monitoring may be used to determine the cerebral autoregulatory capacity and an optimal MAP, but this approach is yet to be tested in clinical trials. Current evidence suggests targeting a MAP of at least 65-75 mmHg in PCA patients. Future studies should focus on whether certain patient groups could benefit from higher and dynamic MAP targets.
  • Kolosowska, Natalia; Gotkiewicz, Maria; Dhungana, Hiramani; Giudice, Luca; Giugno, Rosalba; Box, Daphne; Huuskonen, Mikko T.; Korhonen, Paula; Scoyni, Flavia; Kanninen, Katja M.; Yla-Herttuala, Seppo; Turunen, Tiia A.; Turunen, Mikko P.; Koistinaho, Jari; Malm, Tarja (2020)
    Background Ischemic stroke is a devastating disease without a cure. The available treatments for ischemic stroke, thrombolysis by tissue plasminogen activator, and thrombectomy are suitable only to a fraction of patients and thus novel therapeutic approaches are urgently needed. The neuroinflammatory responses elicited secondary to the ischemic attack further aggravate the stroke-induced neuronal damage. It has been demonstrated that these responses are regulated at the level of non-coding RNAs, especially miRNAs. Methods We utilized lentiviral vectors to overexpress miR-669c in BV2 microglial cells in order to modulate their polarization. To detect whether the modulation of microglial activation by miR-669c provides protection in a mouse model of transient focal ischemic stroke, miR-669c overexpression was driven by a lentiviral vector injected into the striatum prior to induction of ischemic stroke. Results Here, we demonstrate that miR-669c-3p, a member of chromosome 2 miRNA cluster (C2MC), is induced upon hypoxic and excitotoxic conditions in vitro and in two different in vivo models of stroke. Rather than directly regulating the neuronal survival in vitro, miR-669c is capable of attenuating the microglial proinflammatory activation in vitro and inducing the expression of microglial alternative activation markers arginase 1 (Arg1), chitinase-like 3 (Ym1), and peroxisome proliferator-activated receptor gamma (PPAR-gamma). Intracerebral overexpression of miR-669c significantly decreased the ischemia-induced cell death and ameliorated the stroke-induced neurological deficits both at 1 and 3 days post injury (dpi). Albeit miR-669c overexpression failed to alter the overall Iba1 protein immunoreactivity, it significantly elevated Arg1 levels in the ischemic brain and increased colocalization of Arg1 and Iba1. Moreover, miR-669c overexpression under cerebral ischemia influenced several morphological characteristics of Iba1 positive cells. We further demonstrate the myeloid differentiation primary response gene 88 (MyD88) transcript as a direct target for miR-669c-3p in vitro and show reduced levels of MyD88 in miR-669c overexpressing ischemic brains in vivo. Conclusions Collectively, our data provide the evidence that miR-669c-3p is protective in a mouse model of ischemic stroke through enhancement of the alternative microglial/macrophage activation and inhibition of MyD88 signaling. Our results accentuate the importance of controlling miRNA-regulated responses for the therapeutic benefit in conditions of stroke and neuroinflammation.
  • Ottesen, Anett H.; Carlson, Cathrine R.; Eken, Olav Sovik; Sadredini, Mani; Myhre, Peder L.; Shen, Xin; Dalhus, Bjorn; Laver, Derek R.; Lunde, Per Kristian; Kurola, Jouni; Lunde, Marianne; Hoff, Jon Erik; Godang, Kristin; Sjaastad, Ivar; Pettila, Ville; Stridsberg, Mats; Lehnart, Stephan E.; Edwards, Andrew G.; Lunde, Ida G.; Omland, Torbjorn; Stokke, Mathis K.; Christensen, Geir; Rosjo, Helge; Louch, William E. (2019)
    BACKGROUND: Circulating SN (secretoneurin) concentrations are increased in patients with myocardial dysfunction and predict poor outcome. Because SN inhibits CaMKII delta (Ca2+/calmodulin-dependent protein kinase II delta) activity, we hypothesized that upregulation of SN in patients protects against cardiomyocyte mechanisms of arrhythmia. METHODS: Circulating levels of SN and other biomarkers were assessed in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT; n=8) and in resuscitated patients after ventricular arrhythmia-induced cardiac arrest (n=155). In vivo effects of SN were investigated in CPVT mice (RyR2 [ryanodine receptor 2]-R2474S) using adeno-associated virus-9-induced overexpression. Interactions between SN and CaMKII delta were mapped using pull-down experiments, mutagenesis, ELISA, and structural homology modeling. Ex vivo actions were tested in Langendorff hearts and effects on Ca2+ homeostasis examined by fluorescence (fluo-4) and patchclamp recordings in isolated cardiomyocytes. RESULTS: SN levels were elevated in patients with CPVT and following ventricular arrhythmia-induced cardiac arrest. In contrast to NT-proBNP (N-terminal proB- type natriuretic peptide) and hs-TnT (high-sensitivity troponin T), circulating SN levels declined after resuscitation, as the risk of a new arrhythmia waned. Myocardial pro-SN expression was also increased in CPVT mice, and further adeno-associated virus-9-induced overexpression of SN attenuated arrhythmic induction during stress testing with isoproterenol. Mechanistic studies mapped SN binding to the substrate binding site in the catalytic region of CaMKII delta. Accordingly, SN attenuated isoproterenol induced autophosphorylation of Thr287-CaMKII delta in Langendorff hearts and inhibited CaMKII delta-dependent RyR phosphorylation. In line with CaMKII delta and RyR inhibition, SN treatment decreased Ca2+ spark frequency and dimensions in cardiomyocytes during isoproterenol challenge, and reduced the incidence of Ca2+ waves, delayed afterdepolarizations, and spontaneous action potentials. SN treatment also lowered the incidence of early afterdepolarizations during isoproterenol; an effect paralleled by reduced magnitude of L-type Ca2+ current. CONCLUSIONS: SN production is upregulated in conditions with cardiomyocyte Ca2+ dysregulation and offers compensatory protection against cardiomyocyte mechanisms of arrhythmia, which may underlie its putative use as a biomarker in at-risk patients.
  • Skrifvars, Markus B.; Hästbacka, Johanna (2018)
  • Tapani, Karoliina T.; Vanhatalo, Sampsa; Stevenson, Nathan J. (2019)
    The aim of this study was to develop methods for detecting the nonstationary periodic characteristics of neonatal electroencephalographic (EEG) seizures by adapting estimates of the correlation both in the time (spike correlation; SC) and time-frequency domain (time-frequency correlation; TFC). These measures were incorporated into a seizure detection algorithm (SDA) based on a support vector machine to detect periods of seizure and nonseizure. The performance of these nonstationary correlation measures was evaluated using EEG recordings from 79 term neonates annotated by three human experts. The proposed measures were highly discriminative for seizure detection (median AUC(SC): 0.933 IQR: 0.821-0.975, median AUC(TFC): 0.883 IQR: 0.707-0.931). The resultant SDA applied to multi-channel recordings had a median AUC of 0.988 (IQR: 0.931-0.998) when compared to consensus annotations, outperformed two state-of-the-art SDAs (p <0.001) and was noninferior to the human expert for 73/79 of neonates.
  • PIPARI Study Grp (2018)
    The aim of this study is to investigate the working memory (WM) of very-low-birthweight (VLBW, 1500g) children at the age of 11years using Baddeley's WM model. A regional cohort of 95 VLBW children was assessed for the domains of the WM model (central executive [CE], visuospatial sketchpad [VS], and phonological loop [PL]) using subtests from the Working Memory Test Battery for Children (WMTB-C) and the Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV). VLBW children were categorized into three groups according to their degree of brain pathology (normal, minor, or major) in neonatal brain magnetic resonance imaging at the term age, and the WM performance was compared between groups to test norms. The structure of the WM model was studied by analyzing correlations among domains. Even VLBW children with normal cognitive development (general ability index 85) performed worse compared to the test norms (M=100, SD=15) on CE (M=87.64, SD=20.54, p