scholarly journals Lempel-Ziv complexity of the EEG predicts long-term functional recovery after stroke in rats

2018 ◽  
Author(s):  
Susan Leemburg ◽  
Claudio L. Bassetti
Keyword(s):  
Motor Function ◽  
Functional Recovery ◽  
Brain Function ◽  
Complexity Analysis ◽  
Recovery Period ◽  
Artery Occlusion ◽  
Multiscale Entropy ◽  
Experimental Stroke ◽  
Reaching Task ◽  
Post Stroke

AbstractNon-linear complexity of the EEG signal can be used to detect abnormal brain function relating to behavioral deficits. Here, we compare the effects of experimental stroke on EEG complexity using Lempel-Ziv complexity analysis (LZC) and multiscale entropy analysis (SampEn).EEG was recorded in bilateral motor cortex at baseline and during a 30-day recovery period after distal middle cerebral artery occlusion in rats. Motor function was assessed using a single pellet reaching task. Stroke caused an acute drop in both LZC and SampEn in the ipsilesional hemisphere in wakefulness, NREM and REM sleep, as well as reduced pellet reaching success. SampEn reductions persisted for at least 10 days post-stroke, whereas LZC had returned to baseline levels by day 4. EEG complexity in the contralesional hemisphere and in sham-operated animals were unaffected.If EEG complexity reflects post-stroke brain function, post-stroke asymmetry could be used to predict behavioral recovery. In rats, acute LZC asymmetry was significantly correlated with the amount of motor function recovery by post-stroke day 31, but SampEn asymmetry was not. EEG LZC may thus be a useful tool for predicting functional recovery after stroke. MSE could be effective in identifying cortical dysfunction, but does not reflect behavioral outcomes.

scholarly journals Power spectrum slope and motor function recovery after focal cerebral ischemia in the rat

2018 ◽  
Author(s):  
Susan Leemburg ◽  
Bo Gao ◽  
Ertugrul Cam ◽  
Johannes Sarnthein ◽  
Claudio L. Bassetti
Keyword(s):  
Power Spectrum ◽  
Motor Function ◽  
Focal Cerebral Ischemia ◽  
Recovery Period ◽  
Artery Occlusion ◽  
Experimental Stroke ◽  
Stroke Models ◽  
Eeg Changes ◽  
Cerebral Artery Occlusion ◽  
Spectrum Slope

AbstractEEG changes across vigilance states have been observed after ischemic stroke in patients and experimental stroke models, but their relation to functional recovery remains unclear. Here, we evaluate motor function, as measured by single pellet reaching (SPR), as well as local EEG changes in NREM, REM and wakefulness during a 30-day recovery period after middle cerebral artery occlusion (MCAO) or sham surgery in rats. Small cortical infarcts resulted in poor SPR performance and induced widespread changes in EEG spectra in the ipsilesional hemisphere in all vigilance states, without causing major changes in sleep-wake architecture. Ipsilesional 1–4 Hz power was increased after stroke, whereas power in higher frequencies was reduced, resulting in a steeper slope of the power spectrum. Multielectrode array analysis of ipsilesional M1 showed that these spectral changes were present on the microelectrode level throughout M1 and were not related to increased synchronization between electrodes. Spectrum slope was significantly correlated with post-stroke motor function.

Abstract P746: Sex Differences in Cognitive and Psychological Outcomes of Stroke: Impact of Diabetes

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Victoria L Wolf ◽  
Aunay Miller ◽  
Raghavendar Chandran ◽  
Weiguo Li ◽  
Adviye Ergul
Keyword(s):  
Artery Occlusion ◽  
Psychological Outcomes ◽  
Experimental Stroke ◽  
Dark Light ◽  
Stroke Outcomes ◽  
Post Stroke ◽  
Stroke Research ◽  
Y Maze ◽  
Male Animal ◽  
The Impact

Diabetes increases risk and severity of post-stroke cognitive impairment (PSCI), a major cause of disability worldwide. While it is known that females suffer more from PSCI, psychological outcomes and underlying reasons are poorly understood. From a preclinical perspective, potential explanations include 1) use of otherwise healthy animals in experimental stroke research without integration of common comorbid diseases like diabetes into the study design, and 2) optimization of most behavioral tests for sensorimotor and cognitive functions using only male animal models. Our hypothesis is that post-stroke outcomes are sex and comorbid disease-dependent. To test this, we validated the Novel Object Recognition (NOR), Y-maze, and Passive Avoidance (PAT) behavioral paradigms in Ctrl and Diabetic (DM) male (M) and female (F) rats pre- and post-stroke (S) via 60 min. middle cerebral artery occlusion (MCAO). We tested the PAT paradigm with a multi-trial method where the animals were habituated to the dark/light chambers without foot shock and then trained in 3 trials where they received foot shock upon entering the dark. We then tested retention following MCAO for their memory of foot shock 2 weeks prior. Multitrial results suggested that there was no difference between groups in learning to associate the dark chamber with the shock, so we revised the multitrial method into a single-trial method for ongoing retention tests to compare the impact of stroke on shock memory recall. PAT revealed (Table 1) disease- and sex-dependent responses to aversive stimulus. NOR revealed that M-DM-S and F-DM-S rats have decreased exploration time, suggesting that they are unmotivated or depressed. Y-maze indicated that males displayed spatial memory recovery, while females remained impaired. In summary, we have observed numerous sex- and disease-dependent post-stroke outcomes with standard behavioral paradigms, causing us to carefully consider how we evaluate preclinical outcomes.

Abstract WP118: The Flavanol (-)-Epicatechin Improves Functional Recovery In Mice Subjected To Experimental Stroke

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Christopher C Leonardo ◽  
Sean Robbins ◽  
Abdullah A Ahmad ◽  
Sylvain Dore
Keyword(s):  
Functional Recovery ◽  
Transcriptional Activation ◽  
Infarct Volume ◽  
Epidemiological Studies ◽  
Artery Occlusion ◽  
Experimental Stroke ◽  
Adhesive Tape ◽  
Dietary Consumption ◽  
Therapeutic Doses ◽  
Cerebral Artery Occlusion

Background: Epidemiological studies indicate that flavanol consumption reduces the propensity to develop cerebrovascular disease. Available data suggest actions on multiple pro-inflammatory pathways, yet it remains unclear which pathways mediate functional recovery after stroke. Our goal is to begin identifying the mechanisms by which the flavanol (-)-epicatechin (EC) improves anatomical and functional outcomes. Based upon data from initial dose-response experiments, ongoing studies are investigating hypothesized protective pathways involving matrix metalloproteinase-mediated blood brain barrier protection and Nrf2 transcriptional activation. Methods: Male, 8-10wk old C57BL/6 mice were pretreated with EC 90m prior to permanent distal middle cerebral artery occlusion. Vehicle or EC was administered by oral gavage to mimic dietary consumption. Mice were evaluated 1, 4 and 7d post-stroke for performance on various sensorimotor tasks prior to histological assessments. Results: Initial experiments demonstrated that mice treated with 15mg/kg EC showed reduced latency to remove adhesive tape at 1d compared to vehicle controls (n=12, p<0.01). Similarly, immunoreactivity for the microglia/macrophage marker Iba1 was increased in the ipsilateral hemispheres of mice 7d after treatment with vehicle (p<0.01), whereas pretreatment with 15mg/kg blocked this effect (n=4). Mice treated with 15mg/kg also showed a trend toward reduced infarct volume relative to vehicle controls (n=5-9 per group). In subsequent reduced dosing studies, vehicle-treated mice again showed deficiencies in removing adhesive tape at 1d (n=8, p<0.01). Remarkably, mice treated with 15, 10 or 5mg/kg EC showed no deficits. Similarly, vehicle control mice showed grip strength impairments up to 7d (n=8, p<0.05) that were absent in all groups of EC-treated mice. Conclusions: Preventative administration of EC promotes functional recovery in mice subjected to experimental stroke. Investigations are underway to determine the pathways mediated by EC following administration at these therapeutic doses. Together, these data will provide insights into the potential for (-)-epicatechin as a clinical therapeutic.

scholarly journals Impact of Key Nicotinic AChR Subunits on Post-Stroke Pneumococcal Pneumonia

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 253
Author(s):  
Sandra Jagdmann ◽  
Claudia Dames ◽  
Daniel Berchtold ◽  
Katarzyna Winek ◽  
Luis Weitbrecht ◽  
...  
Keyword(s):  
Artery Occlusion ◽  
Experimental Stroke ◽  
Medical Complication ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Post Stroke ◽  
Cholinergic Signaling ◽  
Cerebral Artery Occlusion ◽  
Pathogen Clearance ◽  
The Impact ◽  
Alveolar Capillary

Pneumonia is the most frequent severe medical complication after stroke. An overactivation of the cholinergic signaling after stroke contributes to immunosuppression and the development of spontaneous pneumonia caused by Gram-negative pathogens. The α7 nicotinic acetylcholine receptor (α7nAChR) has already been identified as an important mediator of the anti-inflammatory pathway after stroke. However, whether the α2, α5 and α9/10 nAChR expressed in the lung also play a role in suppression of pulmonary innate immunity after stroke is unknown. In the present study, we investigate the impact of various nAChRs on aspiration-induced pneumonia after stroke. Therefore, α2, α5, α7 and α9/10 nAChR knockout (KO) mice and wild type (WT) littermates were infected with Streptococcus pneumoniae (S. pneumoniae) three days after middle cerebral artery occlusion (MCAo). One day after infection pathogen clearance, cellularity in lung and spleen, cytokine secretion in bronchoalveolar lavage (BAL) and alveolar-capillary barrier were investigated. Here, we found that deficiency of various nAChRs does not contribute to an enhanced clearance of a Gram-positive pathogen causing post-stroke pneumonia in mice. In conclusion, these findings suggest that a single nAChR is not sufficient to mediate the impaired pulmonary defense against S. pneumoniae after experimental stroke.

scholarly journals The Asparaginyl Endopeptidase Legumain after Experimental Stroke

2010 ◽  
Vol 30 (10) ◽  
pp. 1756-1766 ◽  
Author(s):  
Taku Ishizaki ◽  
Agnes Erickson ◽  
Enida Kuric ◽  
Mehrdad Shamloo ◽  
Ikuko Hara-Nishimura ◽  
...  
Keyword(s):  
Immune Cell ◽  
Infarct Volume ◽  
Recovery Period ◽  
Gene Array ◽  
Stroke Recovery ◽  
Experimental Stroke ◽  
Post Stroke ◽  
Asparaginyl Endopeptidase ◽  
Infarct Area ◽  
Deficient Mice

Various proteases in the brain contribute to ischemic brain injury. We investigated the involvement of the asparaginyl endopeptidase legumain after experimental stroke. On the basis of gene array studies and in situ hybridizations, we observed an increase of legumain expression in the peri-infarct area of rats after transient occlusion of the middle cerebral artery (MCAO) for 120 mins with a maximum expression at 24 and 48 h. Immunohistochemical analyses revealed the expression of legumain in Iba1+ microglial cells and glial fibrillary acidic protein-positive astrocytes of the peri-infarct area in mice after MCAO. Post-stroke recovery was also studied in aged legumain-deficient mice (45 to 58 weeks old). Legumain-deficient mice did not show any differences in physiologic parameters compared with respective littermates before, during MCAO (45 mins), and the subsequent recovery period of 8 days. Moreover, legumain deficiency had no effect on mortality, infarct volume, and the neurologic deficit determined by the rotating pole test, a standardized grip strength test, and the pole test. However, a reduced number of invading CD74+ cells in the ischemic hemisphere indicates an involvement in post-stroke inflammation. We conclude that legumain is not essential for the functional deficit after MCAO but may be involved in mechanisms of immune cell invasion.

scholarly journals Enriched Environment Reduces Apolipoprotein E (ApoE) in Reactive Astrocytes and Attenuates Inflammation of the Peri-Infarct Tissue after Experimental Stroke

2009 ◽  
Vol 29 (11) ◽  
pp. 1796-1805 ◽  
Author(s):  
Karsten Ruscher ◽  
Emelie Johannesson ◽  
Elena Brugiere ◽  
Agnes Erickson ◽  
Mattias Rickhag ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Interleukin 1 ◽  
Recovery Period ◽  
Artery Occlusion ◽  
Enriched Environment ◽  
Reactive Astrocytes ◽  
Experimental Stroke ◽  
Housing Conditions ◽  
Tissue Reorganization ◽  
Cerebral Artery Occlusion

Apolipoprotein E (ApoE), a cholesterol transporter and an immunomodulator, is brain protective after experimental stroke and implicated in brain repair. Here, we study the involvement of ApoE in the restoration of brain function after experimental stroke, by using animal housing conditions that differentially improve recovery after occlusion of the middle cerebral artery occlusion (MCAO). We found that after MCAO the ApoE levels increased in the injured hemisphere over a 30 days recovery period. The exception was a proximal narrow peri-infarct rim, in which ApoE was solely localized in S100 β+/glial fibrillary acidic protein (GFAP) negative reactive astrocytes at 4 to 7 days of recovery. Enriched housing after MCAO caused a marked decrease in ApoE levels compared with standard housing conditions, particularly in the ApoE/S100 β+ reactive astrocytes. In addition, the levels of interleukin 1 β were lower in animals housed in an enriched environment. We propose that during the subacute phase after experimental stroke a zone for tissue reorganization with low cellular ApoE levels is formed. We conclude that the strong sensori-motor stimulation provided by enriched housing conditions mitigates the inflammatory response after stroke decreasing the level of ApoE that may contribute to the observed improvement of functional recovery.

A Mouse Model of Post-Stroke Pneumonia Induced by Intra-Tracheal Inoculation with Streptococcus pneumoniae

2017 ◽  
Vol 43 (3-4) ◽  
pp. 99-109 ◽  
Author(s):  
Eva Mracsko ◽  
Sabine Stegemann-Koniszewski ◽  
Shin-Young Na ◽  
Alexander Dalpke ◽  
Dunja Bruder ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Mouse Model ◽  
Bacterial Pneumonia ◽  
Cytokine Production ◽  
Infectious Complications ◽  
Artery Occlusion ◽  
Experimental Stroke ◽  
Bacterial Counts ◽  
Post Stroke ◽  
Humoral Immune

Background: Stroke-induced immunodeficiency increases the risk of infectious complications, which adversely affects neurological outcome. Among those, pneumonia affects as many as one third of stroke patients and is the main contributor to mortality in the post-acute phase of stroke. Experimental findings on post-stroke susceptibility to spontaneous pneumonia in mice are contradictory. Here, we established a mouse model inducing standardized bacterial pneumonia and characterized the impaired pulmonary cellular and humoral immune responses after experimental stroke. Methods: Bacterial pneumonia was induced by intra-tracheal inoculation with Streptococcus pneumoniae at different time points after transient middle cerebral artery occlusion (MCAO). Bacterial counts in lungs and blood, histological changes, and cytokine production in the lungs were assessed. Furthermore, we investigated the effect of pneumonia on stroke outcome. Results: Intra-tracheal inoculation resulted in reproducible pneumonia and bacteraemia, and demonstrated post-stroke susceptibility to streptococcal pneumonia developing with a delay of at least 24 h after MCAO. Higher bacterial counts in mice infected 3 days after stroke induction correlated with reduced neutrophil and macrophage infiltration in the lungs and lower levels of pro-inflammatory cytokines in the broncho-alveolar lavage compared to sham-operated animals. Pneumonia increased mortality without affecting brain-infiltrating leukocytes. Conclusions: In this standardized mouse model of post-stroke pneumonia, we describe attenuated leukocyte infiltration and cytokine production in response to bacterial infection in the lungs that has a profound effect on outcome.

Abstract 12: S-Nitrosylation Invokes Functional Recovery from Experimental Stroke through the Hypoxia-inducible Factor-1 alpha/Vascular Endothelial Growth Factor Pathway

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Mushfiquddin Khan ◽  
Tajinder S Dhammu ◽  
Fumiyo Matsuda ◽  
Inderjit Singh ◽  
Avtar K Singh
Keyword(s):  
Functional Recovery ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Hypoxia Inducible Factor ◽  
Artery Occlusion ◽  
Tube Formation ◽  
Male Rats ◽  
Experimental Stroke ◽  
Capillary Endothelial Cells ◽  
Stimulation Of

Background: In stroke patients, the stimulation of neurorepair mechanisms is necessary to reduce morbidity and disability. Our studies on brain and spinal cord trauma show that an exogenous treatment with the S-nitrosylating agent S-nitrosoglutathione (GSNO) stimulates neurorepair and aids functional recovery. Using a rat model of cerebral ischemia reperfusion (IR), we tested the hypothesis that GSNO invokes the neurorepair process and improves neurobehavioral functions through the angiogenic HIF-1α/VEGF pathway. Methods: Stroke was induced by middle cerebral artery occlusion for 60 min followed by reperfusion in adult male rats. The injured animals were treated with vehicle (IR group, n=7), GSNO (0.25 mg/kg, GSNO group, n=7), and GSNO plus the HIF-1α inhibitor 2-mthoxyestradiol (0.25 mg/kg GSNO+5.0 mg/kg ME, GSNO+ME group, n=7). The groups were studied for 14 days to determine neurorepair mechanisms and functional recovery. Brain capillary endothelial cells were used to show that GSNO promotes angiogenesis and that GSNO-mediated induction of VEGF and the stimulation of angiogenesis are dependent on HIF-1α activity. Results: GSNO treatment of IR enhanced the expression of HIF-1α, VEGF, and PECAM-1. This GSNO treatment also led to increased expression of neurorepair mediators including BDNF. Increased expression of VEGF/BDNF and the degree of tube formation (angiogenesis) by GSNO were reduced in an endothelial cell culture model after the inhibition of HIF-1α by ME. ME treatment of the GSNO group also blocked not only GSNO’s effect of reduced infarct volume (p<0.05) and enhanced expression of PECAM-1but also its improvement of motor and neurological functions (p<0.001). Conclusions: GSNO shows therapeutic promise for stroke by stimulating the process of neurorepair and aiding functional recovery through the HIF-1α/VEGF/PECAM-1 dependent pathway.

Abstract P733: Astroglial Activation Following Stroke Contributes to Impaired Synaptic Plasticity Through Increased Cd38-trpm2 Channel Signaling

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Amelia M Burch ◽  
James E Orfila ◽  
Robert Dietz ◽  
Andra Dingman ◽  
Danae Mitchell ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Memory Function ◽  
Hippocampal Slices ◽  
Brain Slices ◽  
Artery Occlusion ◽  
Experimental Stroke ◽  
Post Stroke ◽  
Cd38 Expression ◽  
Trpm2 Channel ◽  
Electrophysiological Recordings

Introduction: Post-stroke cognitive impairment (PSCI) is a major contributor to long-term disability following acute ischemic stroke. Learning and memory deficits are a common feature of PSCI and alterations in hippocampal function are a likely contributor. Interestingly, common experimental stroke models (middle cerebral artery occlusion; MCAO) cause hippocampal dysfunction, despite no direct ischemic insult to the hippocampus, suggesting perturbations in neural circuits. Thus, we utilize electrophysiological recordings of hippocampal plasticity in combination with neurobehavioral assessments of memory function. Hypothesis: Activated astrocytes in the hippocampus following MCAO increase expression of the surface enzyme CD38, which signals to neurons to impair plasticity. Methods: Extracellular field recordings of CA1 neurons were performed in acute hippocampal slices prepared 30 days after recovery from transient MCAO (60 min) in adult (6-8 week) mice. A behavioral fear conditioning paradigm (CFC) was used to evaluate contextual memory. Immunohistochemistry was performed to assess CD38 expression and slices were treated with CD38 inhibitors (78c) to assess plasticity. Results: Recordings obtained in brain slices 30 days after MCAO exhibited loss of hippocampal LTP; 134±6%, n=4 in sham and 107±12%, n=4 30 days after MCAO. Memory function, measured using CFC, was consistent with our LTP findings. MCAO decreased freezing behavior, indicating lack of memory (65±7% in sham mice (n=6) and 37±7% in MCAO mice, n=7). Immunohistochemical data indicates increased CD38 expression in activated astrocytes following MCAO in the hippocampus. Treatment of hippocampal slices with 78c, a potent CD38 inhibitor, after MCAO rescues LTP impairment. Finally, no additive increase in LTP when 78c is co-administered with a TRPM2 channel inhibitor was observed. Conclusion: These data indicate that MCAO is a reproducible model of post-stroke memory dysfunction (PSCI) and remote astrogliosis in the uninjured hippocampus may contribute to altered neuronal function (plasticity). Our data implicates increased levels of CD38 as an upstream activator of neuronal TRPM2 channel in the hippocampus following stroke, resulting in impaired synaptic plasticity.

scholarly journals Effects of Tetramethylpyrazine on Functional Recovery and Neuronal Dendritic Plasticity after Experimental Stroke

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Jun-Bin Lin ◽  
Chan-Juan Zheng ◽  
Xuan Zhang ◽  
Juan Chen ◽  
Wei-Jing Liao ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Functional Recovery ◽  
Classical Model ◽  
Significant Negative Correlation ◽  
Artery Occlusion ◽  
Neurological Function ◽  
Experimental Stroke ◽  
Spine Density ◽  
Dendritic Plasticity ◽  
Cerebral Artery Occlusion

The 2,3,5,6-tetramethylpyrazine (TMP) has been widely used in the treatment of ischemic stroke by Chinese doctors. Here, we report the effects of TMP on functional recovery and dendritic plasticity after ischemic stroke. A classical model of middle cerebral artery occlusion (MCAO) was established in this study. The rats were assigned into 3 groups: sham group (sham operated rats treated with saline), model group (MCAO rats treated with saline) and TMP group (MCAO rats treated with 20 mg/kg/d TMP). The neurological function test of animals was evaluated using the modified neurological severity score (mNSS) at 3 d, 7 d, and 14 d after MCAO. Animals were euthanized for immunohistochemical labeling to measure MAP-2 levels in the peri-infarct area. Golgi-Cox staining was performed to test effect of TMP on dendritic plasticity at 14 d after MCAO. TMP significantly improved neurological function at 7 d and 14 d after ischemia, increased MAP-2 level at 14 d after ischemia, and enhanced spine density of basilar dendrites. TMP failed to affect the spine density of apical dendrites and the total dendritic length. Data analyses indicate that there was significant negative correlation between mNSS and plasticity measured at 14 d after MCAO. Thus, enhanced dendritic plasticity contributes to TMP-elicited functional recovery after ischemic stroke.

Sign in / Sign up

Export Citation Format

Share Document