Neuroplasticity Markers Research Articles

Intensity matters: protocol for a randomized controlled trial exercise intervention for individuals with chronic stroke

RationaleCardiovascular exercise is an effective method to improve cardiovascular health outcomes, but also promote neuroplasticity during stroke recovery. Moderate-intensity continuous cardiovascular training (MICT) is an integral part of stroke rehabilitation, yet it may remain a challenge to exercise at sufficiently high intensities to produce beneficial adaptations to neuroplasticity. High-intensity interval training (HIIT) could provide a viable alternative to achieve higher intensities of exercise by using shorter bouts of intense exercise interspersed with periods of recovery.Methods and designThis is a two-arm, parallel-group multi-site RCT conducted at the Jewish Rehabilitation Hospital (Laval, Québec, Canada) and McMaster University (Hamilton, Ontario, Canada). Eighty participants with chronic stroke will be recruited at both sites and will be randomly allocated into a HIIT or MICT individualized exercise program on a recumbent stepper, 3 days per week for 12 weeks. Outcomes will be assessed at baseline, at 12 weeks post-intervention, and at an 8-week follow-up.OutcomesThe primary outcome is corticospinal excitability, a neuroplasticity marker in brain motor networks, assessed with transcranial magnetic stimulation (TMS). We will also examine additional markers of neuroplasticity, measures of cardiovascular health, motor function, and psychosocial responses to training.DiscussionThis trial will contribute novel insights into the effectiveness of HIIT to promote neuroplasticity in individuals with chronic stroke.Trial registrationClinicalTrials.govNCT03614585. Registered on 3 August 2018

Upregulation of Neuroplasticity Marker Doublecortin in the Human Post-Mortem Brain After Electroconvulsive Therapy

Electroconvulsive therapy (ECT) is currently the most effective therapy in psychiatry, but the exact working cellular mechanism is still unknown. In MRI studies, a consistent increased hippocampal volume is found, with a more recent study revealing the dentate gyrus (DG) to show the largest increase in volume. The current debate focuses on if this increased volume is due to neurogenesis or secondary factors such as gliosis. Rodent models revealed that after repeated administration of electroconvulsive shocks, the hippocampus shows increased expression of cell proliferation markers, suggesting neurogenesis.

Effects of air pollution exposure on inflammatory and endurance performance in recreationally trained cyclists adapted to traffic-related air pollution.

The aim of the present study was to analyze the effects of traffic-related air pollution (TRAP) on markers of inflammatory, neuroplasticity, and endurance performance-related parameters in recreationally trained cyclists who were adapted to TRAP during a 50-km cycling time trial (50-km cycling TT). Ten male cyclists performed a 50-km cycling TT inside an environmental chamber located in downtown Sao Paulo (Brazil), under TRAP or filtered air conditions. Blood samples were obtained before and after the 50-km cycling TT to measure markers of inflammatory [interleukin-6 (IL-6), C-reactive protein (CRP), interleukin-10 (IL-10), intercellular adhesion molecule-1 (ICAM-1)] and neuroplasticity [brain-derived neurotrophic factor (BDNF)]. Rating of perceived exertion (RPE), heart rate (HR), and power output (PO) were measured throughout the 50-km cycling TT. There were no significant differences between experimental conditions for responses of IL-6, CRP, and IL-10 (P > 0.05). When compared with exercise-induced changes in filtered air condition, TRAP provoked greater exercise-induced increase in BDNF levels (TRAP = 3.3 ± 2.4-fold change; Filtered = 1.3 ± 0.5-fold change; P = 0.04) and lower exercise-induced increase in ICAM-1 (Filtered = 1.1 ± 0.1-fold change; TRAP = 1.0 ± 0.1-fold change; P = 0.01). The endurance performance-related parameters (RPE, HR, PO, and time to complete the 50-km cycling TT) were not different between TRAP and filtered air conditions (P > 0.05). These findings suggest that the potential negative impacts of exposure to pollution on inflammatory, neuroplasticity, and performance-related parameters do not occur in recreationally trained cyclists who are adapted to TRAP.

Hair-cortisol and hair-BDNF as biomarkers of tinnitus loudness and distress in chronic tinnitus

The role of stress and its neuroendocrine mediators in tinnitus is unclear. In this study, we measure cortisol as an indicator of hypothalamus–pituitary–adrenal (HPA) axis alterations and brain-derived neurotrophic factor (BDNF) as a marker of adaptive neuroplasticity in hair of chronic tinnitus patients to investigate relationships with tinnitus-related and psychological factors. Cross-sectional data from chronic tinnitus inpatients were analyzed. Data collection included hair sampling, pure tone audiometry, tinnitus pitch and loudness matching, and psychometric questionnaires. Elastic net regressions with n-fold cross-validation were performed for cortisol (N = 91) and BDNF (N = 87). For hair-cortisol (R2 = 0.10), the strongest effects were sampling in autumn and body-mass index (BMI) (positive), followed by tinnitus loudness (positive) and smoking (negative). For hair-BDNF (R2 = 0.28), the strongest effects were hearing aid use, shift work (positive), and tinnitus loudness (negative), followed by smoking, tinnitus-related distress (Tinnitus Questionnaire), number of experienced traumatic events (negative), and physical health-related quality of life (Short Form-12 Health Survey) (positive). These findings suggest that in chronic tinnitus patients, higher perceived tinnitus loudness is associated with higher hair-cortisol and lower hair-BDNF, and higher tinnitus-related distress with lower hair-BDNF. Regarding hair-BDNF, traumatic experiences appear to have additional stress-related effects, whereas hearing aid use and high physical health-related quality of life appear beneficial. Implications include the potential use of hair-cortisol and hair-BDNF as biomarkers of tinnitus loudness or distress and the need for intensive future research into chronic stress-related HPA axis and neuroplasticity alterations in chronic tinnitus.

Sleep EEG-pattern alteration as a specific marker of neuroplasticity in intellectually gifted schoolchildren

BACKGROUND: At school, children constantly acquire new knowledge, which provokes changes in the brain structures, especially during intensive learning. Neuroplasticity enables a person to realize his potential, to show giftedness. However, data on electroencephalographic (EEG) features during the sleep in gifted schoolchildren are insufficient and contradictory.
 AIM: To study the features of EEG sleep patterns according to neurophysiological research data in intellectually gifted schoolchildren and their correlation with verbal and non-verbal mental abilities.
 MATERIALS AND METHODS: 48 lyceum students aged 14-15 years were examined. All participants were performed the Wechsler-Intelligence test (childrens version) to determine them intelligence quotient (IQ). Two groups of adolescents were identified: the main group (n = 20) with a high IQ (137.012.7 points), the control group (n = 28) with an average IQ (110.910.4 points). Neurophysiological examination during the sleep was performed using an ambulatory wireless system for registration of electroencephalograms and polysomnograms Neuron-Spectrum-AM (Neurosoft, Ivanovo, Russian Federation,). The identification and analysis of EEG sleep patterns: cyclic alternating patterns and sleep spindles were carried out according to standard methods. Differences between groups were considered statistically significant at p 0.05.
 RESULTS: In gifted schoolchildren, significant changes were revealed as an increase in the time and the rate of cyclic alternating patterns with a predominance of A1 subtype (p = 0.0001) and a decrease in the proportion of А2-A3 subtypes, as well as an increase of sleep spindles density (p = 0.01), which significantly correlated with the Wechsler-Intelligence Tests scores. So, percentage of A1 subtype had correlation with the index of thinking flexibility, while percentage of A2 subtype correlated with general and non-verbal intelligence, non-verbal visual-spatial abilities, the index of working memory) and the index of verbal perception, as well as the sleep spindles index and sleep spindles frequency peak correlated with the index of verbal perception, the index of working memory, the index of information processing speed and general intelligence.
 CONCLUSIONS: Thus, we have demonstrated significant changes in the sleep microstructure and different correlations depending on the IQ values in schoolchildren, which was not previously covered in the literature. Cyclic alternating patterns and sleep spindles are recommended to be considered as physiological indicators of intelligence and academic performance, as well as specific markers of neuroplasticity in the intensification of learning.

Regulation of neurogenesis and cerebral angiogenesis by cell protein proteolysis products

Brain development is a unique process characterized by mechanisms defined as neuroplasticity (synaptogenesis, synapse elimination, neurogenesis, and cerebral angiogenesis). Numerous neurodevelopmental disorders brain damage, and aging are manifested by neurological deficits that are caused by aberrant neuroplasticity. The presence of stem and progenitor cells in neurogenic niches of the brain is responsible for the formation of new neurons capable of integrating into preexisting synaptic assemblies. The determining factors for the cells within the neurogenic niche are the activity of the vascular scaffold and the availability of active regulatory molecules that establish the optimal microenvironment. It has been found that regulated intramembrane proteolysis plays an important role in the control of neurogenesis in brain neurogenic niches. Molecules generated by the activity of specific proteases can stimulate or suppress the activity of neural stem and progenitor cells, their proliferation and differentiation, migration and integration of newly formed neurons into synaptic networks. Local neoangiogenesis supports the processes of neurogenesis in neurogenic niches, which is guaranteed by the multivalent action of peptides formed from transmembrane proteins. Identification of new molecules regulating the neuroplasticity (neurogenesis and angiogenesis). i. e. enzymes, substrates, and products of intramembrane proteolysis, will ensure the development of protocols for detecting the neuroplasticity markers and targets for efficient pharmacological modulation.

Combined treatment with exercise and α5GABAAR inhibitor promotes motor function recovery after intracerebral hemorrhage

The present study aimed to examine the synergistic effects of exercise and pharmacological inhibition of the α5 subunit-containing gamma-aminobutyric acid (GABA)A receptors (α5GABAAR) on motor function recovery after intracerebral hemorrhage (ICH). Wistar rats were divided into five groups (n = 8 per group): SHAM, ICH, ICH + exercise (ICH + EX), ICH + L-655,708 (ICH + L6), and ICH + L-655,708 and exercise (ICH + L6EX) groups. ICH was induced by microinjection of a collagenase solution. The ICH + EX and ICH + L6EX groups exercised on a treadmill (12 m/min for 30 min/day). L-655,708 (0.5 mg/kg), a negative allosteric modulator of α5GABAAR, was administered intraperitoneally to the ICH + L6 and ICH + L6EX groups. Each intervention was initiated 1 week after the ICH surgery and was performed for 3 weeks, followed by tissue collection, including the motor cortex and spinal cord. At 4 weeks after ICH, significant motor recovery was found in the ICH + L6EX group compared to the ICH group. L-655,708 administration increased brain-derived neurotrophic factor (BDNF) expression in the cortex. Regarding neuroplastic changes in the spinal cord, rats in the ICH + L6EX group showed a significant increase in several neuroplastic markers: 1) BDNF, 2) growth-associated protein 43 as an axonal sprouting marker, 3) synaptophysin as a synaptic marker, and 4) Nogo-A as an axonal growth inhibitor. This study is the first to demonstrate that combined treatment with exercise and α5GABAAR inhibitor effectively promoted motor function recovery after ICH. Regarding the underlying mechanism of post-ICH recovery with the combined treatment, the present study highlights the importance of both growth and inhibitory modification of axonal sprouting in the spinal cord.

Resting-State Functional Connectivity following Phonological Component Analysis: The Combined Action of Phonology and Visual Orthographic Cues.

Anomia is the most frequent and pervasive symptom for people with aphasia (PWA). Phonological component analysis (PCA) is a therapy incorporating phonological cues to treat anomia. Investigations of neural correlates supporting improvements following PCA remain scarce. Resting-state functional connectivity (rsFC) as a marker of therapy-induced neuroplasticity has been reported by our team. The present study explores the efficacy of PCA in French and associated therapy-induced neuroplasticity using whole-brain rsFC analysis. Ten PWA participated in a pre-/post-PCA fMRI study with cognitive linguistic assessments. PCA was delivered in French following the standard procedure. PCA led to significant improvement with trained and untrained items. PCA also led to changes in rsFC between distributed ROIs in the semantic network, visual network, and sub-cortical areas. Changes in rsFC can be interpreted within the frame of the visual and phonological nature of PCA. Behavioral and rsFC data changes associated with PCA in French highlight its efficacy and point to the importance of phonological and orthographic cues to consolidate the word-retrieval strategy, contributing to generalization to untrained words.

Whole-body repeated hyperthermia increases irisin and brain-derived neurotrophic factor: A randomized controlled trial.

Hyperthermia is known to be beneficial to patients affected by various diseases. Irisin is a key regulators of fat metabolism known to be released as response to cold. Brain Derived Neurotrophic Factor (BDNF) is a marker of neuroplasticity usually increased as response to acute exposure to human body stressors. Effect of a repeated hyperthermia exposure programme on changes in circulating irisin and serum BDNF in healthy humans. Setting, Participants: Randomized, single-blind, cross-over trial in healthy humans conducted at Sechenov University Physiology Laboratory from April 2019. The treatment period was 2 weeks (wash-out 3 weeks). Researchers analysing serum biomarkers and questionnaires data were blinded to participants allocation. Participants were 20 healthy male (age 21.5±2.1 years). Hyperthermia exposure programme (WBPH) versus sham exposure (SHAM) to hyperthermia (10 sessions in two weeks). Changes in irisin and BDNF before and after short hyperthermia exposure. Twenty participants were analyzed. Irisin increased significantly in group WBPH only: 6.3μg/ml (mean with SD=1.6) compared to 5.4μg/ml (SD=1.7) in SHAM group; This value was also higher than baseline (5.0 mean with SD=1.1) in WBPH. After 10 sessions mean change in BDNF was higher in WBPH group vs SHAM: BDNF was 28,263 (SD=4213) pg/ml in WBPH group and 24,064 (SD=5600) pg/ml in SHAM group. BDNF concentrations were significantly higher than baseline values in WBPH group only, 28,263 (SD 4213) vs 25,888 (SD 4316) pg/ml. In healthy young humans a 2-week, ten sessions programme consisting of repeated exposure to hyperthermia resulted in a significantly higher increase of circulating Irisin and BDNF.

Dose-dependent opposite effects of nortriptyline on affective-like behavior in adolescent rats: Comparison with adult rats

Antidepressant drugs elicit different behavioral and neurochemical responses with age. In fact, the use of antidepressants during adolescence is associated with an increased risk of suicidal thinking, being the best pharmacological treatment during this critical period a matter of constant debate in terms of its risk-benefit outcome. In this regard, the present study compared the effects of nortriptyline (3–10 mg/kg, 7 days) on regulating different aspects of affective-like behavior by screening adolescent and adult Sprague-Dawley rats through several consecutive tests (forced-swim, open field, sucrose preference). Brains were later collected to evaluate hippocampal neurogenesis and mBDNF protein content as potential molecular correlates of the observed behavioral responses. The main results in adolescent rats showed that nortriptyline induced dose-dependent opposite effects: while 3 mg/kg decreased immobility and increased mBDNF (indicative of an antidepressant-like response), 10 mg/kg decreased exploratory time in the open field and mBDNF (suggestive of an anxiogenic-like response). These effects were not associated with changes in neurogenesis regulation. In adult rats, nortriptyline failed to modulate affective-like behavior or the neuroplasticity markers evaluated at the doses tested. In conclusion, clear behavioral and neurochemical differences were observed between adolescent and adult rats in response to nortriptyline treatment. Interestingly, while nortriptyline displayed an antidepressant-like potential at the lowest dose examined in adolescence, a higher dose shifted these results towards a negative outcome, thus reinforcing the need to extreme caution when considering this treatment for our younger population.

Deficit of Inhibition as a Marker of Neuroplasticity (DEFINE Study) in Rehabilitation: A Longitudinal Cohort Study Protocol.

Background: Brain plasticity is an intrinsic property of the nervous system, which is modified during its lifetime. This is one mechanism of recuperation after injuries with an important role in rehabilitation. Evidence suggests that injuries in the nervous system disturb the stability between inhibition and excitability essential for the recuperation process of neuroplasticity. However, the mechanisms involved in this balance are not completely understood and, besides the advancement in the field, the knowledge has had a low impact on the rehabilitation practice. Therefore, the understanding of the relationship between biomarkers and functional disability may help to optimize and individualize treatments and build consistent studies in the future.Methods: This cohort study, the deficit of inhibition as a marker of neuroplasticity study, will follow four groups (stroke, spinal cord injury, limb amputation, and osteoarthritis) to understand the neuroplasticity mechanisms involved in motor rehabilitation. We will recruit 500 subjects (including 100 age- and sex-matched controls). A battery of neurophysiological assessments, transcranial magnetic stimulation, electroencephalography, functional near-infrared spectroscopy, and magnetic resonance imaging, is going to be used to assess plasticity on the motor cortex before and after rehabilitation. One of the main hypotheses in this cohort is that the level of intracortical inhibition is related to functional deficits. We expect to develop a better understanding of the neuroplasticity mechanisms involved in the rehabilitation, and we expect to build neurophysiological “transdiagnostic” biomarkers, especially the markers of inhibition, which will have great relevance in the scientific and therapeutic improvement in rehabilitation. The relationship between neurophysiological and clinical outcomes will be analyzed using linear and logistic regression models.Discussion: By evaluating the reliability of electroencephalography, functional near-infrared spectroscopy, transcranial magnetic stimulation, and magnetic resonance imaging measures as possible biomarkers for neurologic rehabilitation in different neurologic disorders, this study will aid in the understanding of brain plasticity mechanisms in rehabilitation, allowing more effective approaches and screening methods to take place.

Antibody Protection against Long-Term Memory Loss Induced by Monomeric C-Reactive Protein in a Mouse Model of Dementia.

Monomeric C-reactive protein (mCRP), the activated isoform of CRP, induces tissue damage in a range of inflammatory pathologies. Its detection in infarcted human brain tissue and its experimentally proven ability to promote dementia with Alzheimer’s disease (AD) traits at 4 weeks after intrahippocampal injection in mice have suggested that it may contribute to the development of AD after cerebrovascular injury. Here, we showed that a single hippocampal administration of mCRP in mice induced memory loss, lasting at least 6 months, along with neurodegenerative changes detected by increased levels of hyperphosphorylated tau protein and a decrease of the neuroplasticity marker Egr1. Furthermore, co-treatment with the monoclonal antibody 8C10 specific for mCRP showed that long-term memory loss and tau pathology were entirely avoided by early blockade of mCRP. Notably, 8C10 mitigated Egr1 decrease in the mouse hippocampus. 8C10 also protected against mCRP-induced inflammatory pathways in a microglial cell line, as shown by the prevention of increased generation of nitric oxide. Additional in vivo and in vitro neuroprotective testing with the anti-inflammatory agent TPPU, an inhibitor of the soluble epoxide hydrolase enzyme, confirmed the predominant involvement of neuroinflammatory processes in the dementia induced by mCRP. Therefore, locally deposited mCRP in the infarcted brain may be a novel biomarker for AD prognosis, and its antibody blockade opens up therapeutic opportunities for reducing post-stroke AD risk.

Single Exposure to the Cathinones MDPV and α-PVP Alters Molecular Markers of Neuroplasticity in the Adult Mouse Brain.

Synthetic cathinones have gained popularity among young drug users and are widely used in the clandestine market. While the cathinone-induced behavioral profile has been extensively investigated, information on their neuroplastic effects is still rather fragmentary. Accordingly, we have exposed male mice to a single injection of MDPV and α-PVP and sacrificed the animals at different time points (i.e., 30 min, 2 h, and 24 h) to have a rapid readout of the effect of these psychostimulants on neuroplasticity in the frontal lobe and hippocampus, two reward-related brain regions. We found that a single, low dose of MDPV or α-PVP is sufficient to alter the expression of neuroplastic markers in the adult mouse brain. In particular, we found increased expression of the transcription factor Npas4, increased ratio between the vesicular GABA transporter and the vesicular glutamate transporter together with changes in the expression of the neurotrophin Bdnf, confirming the widespread impact of these cathinones on brain plasticity. To sum up, exposure to low dose of cathinones can impair cortical and hippocampal homeostasis, suggesting that abuse of these cathinones at much higher doses, as it occurs in humans, could have an even more profound impact on neuroplasticity.

How do serotonergic psychedelics treat depression: The potential role of neuroplasticity

Depression is a common mental disorder and one of the leading causes of disability around the world. Monoaminergic antidepressants often take weeks to months to work and are not effective for all patients. This has led to a search for a better understanding of the pathogenesis of depression as well as to the development of novel antidepressants. One such novel antidepressant is ketamine, which has demonstrated both clinically promising results and contributed to new explanatory models of depression, including the potential role of neuroplasticity in depression. Early clinical trials are now showing promising results of serotonergic psychedelics for depression; however, their mechanism of action remains poorly understood. This paper seeks to review the effect of depression, classic antidepressants, ketamine, and serotonergic psychedelics on markers of neuroplasticity at a cellular, molecular, electrophysiological, functional, structural, and psychological level to explore the potential role that neuroplasticity plays in the treatment response of serotonergic psychedelics.

Neurotrophic Treatment Initiated During Early Postnatal Development Prevents the Alzheimer-Like Behavior and Synaptic Dysfunction.

Background:Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by impairments in synaptic plasticity and cognitive performance. Cognitive dysfunction and loss of neuronal plasticity are known to begin decades before the clinical diagnosis of the disease. The important influence of congenital genetic mutations on the early development of AD provides a novel opportunity to initiate treatment during early development to prevent the Alzheimer-like behavior and synaptic dysfunction.Objective:To explore strategies for early intervention to prevent Alzheimer’s disease.Methods:In the present study, we investigated the effect of treatment during early development with a ciliary neurotrophic factor (CNTF) derived peptidergic compound, P021 (Ac-DGGLAG-NH2) on cognitive function and synaptic plasticity in 3xTg-AD transgenic mouse model of AD. 3xTg-AD and genetic background-matched wild type female mice were treated from birth to postnatal day 120 with P021 in diet or as a control with vehicle diet, and cognitive function and molecular markers of neuroplasticity were evaluated.Results:P021 treatment during early development prevented cognitive impairment and increased expressions of pCREB and BDNF that activated downstream various signaling cascades such as PLC/PKC, MEK/ERK and PI3K/Akt, and ameliorated synaptic protein deficit in 4-month-old 3xTg-AD mice.Conclusion:These findings indicate that treatment with the neurotrophic peptide mimetic such as P021 during early development can be an effective therapeutic strategy to rescue synaptic deficit and cognitive impairment in familial AD and related tauopathies.

The mechanisms of neuroplasticity during acclimatization to‐ and deacclimatization from chronic hypercapnia are fundamentally different

A hallmark of respiratory-related diseases, such as chronic obstructive pulmonary disease (COPD), is chronic hypercapnia (CH). Common therapeutic intervention for patients experiencing CH is mechanical ventilation to restore blood-gas homeostasis. While many neurophysiological consequences of CH have been characterized, little is known about the effects reversing CH. The primary goal of the present study was to test the hypothesis that abrupt deacclimatization from CH would significantly alter markers of neuroplasticity and tryptophan metabolism, but not levels of excitatory neuromodulators. Utilizing our goat model of increased inspired CO2 (InCO2)-induced CH, adult female goats were exposed to an InCO2 of 6% for 30 days (d) followed by a return to room air for 24 hours (h). Following 24h of recovery, goats were euthanized, and brainstems were rapidly extracted. Tissue punches of key nuclei throughout the brainstem respiratory network (hypoglossal motor nucleus (XII), nucleus tractus solitarius (NTS)/dorsal motor nucleus of the vagus (DMV), ventral respiratory column (VRC), medullary raphe (MR), ventrolateral medulla (VLM), retrotrapezoid nucleus (RTN), and cuneate nucleus (CN)) were obtained and used for either western blot or HPLC analysis. Changes in glutamatergic signaling, neuroinflammation, tryptophan metabolism, and neuromodulators concentration, following recovery from CH, were assessed. Following 24h of recovery, there were no significant differences in AMPA or NMDA receptor expression or phosphorylation, compared to room air control goats, across all nuclei investigated. Similarly, there were no significant differences in the inflammatory cytokine IL1B following 24h recovery across all nuclei investigated, compared to room air control goats. However, there was significantly (P<0.05) lower expression of key enzymes of tryptophan metabolism (Indolamine 2,3-dioxygenase (IDO); Tryptophan Hydroxylase (TPH) and neuronal markers (NeuN) compared to control within the rostral VLM and MR. Within the solitary complex (NTS & DMV), there was significantly (P>0.05) greater concentrations in norepinephrine (+132%±49), serotonin (+348%±142), and dopamine (+86%±53) at 24h of recovery compared to 30d of CH. We conclude that although specific markers of neuroplasticity and neuroinflammation were unchanged from control during deacclimatization, there were brainstem-site dependent changes in excitatory neuromodulators during deacclimatization from CH. These data suggest that the mechanisms of neuroplasticity during acclimatization to- and deacclimatization from- CH are fundamentally different.

The use of recombinant tissue plasminogen activator in in acute ischemic stroke is associated with increased level of BDNF.

Much concern was directed towards the crucial role of recombinant tissue plasminogen activator (rt-PA) in improving neuroplasticity in patients with acute ischemic stroke. The aim of the work to investigate the effect of treating patients with acute ischemic stroke with rt-PA, on the level of brain derived neurotrophic factor (BDNF) as a marker of neuroplasticity. This study was conducted on 47 patients presenting with acute ischemic stroke (during the first 4.5h from stroke onset); 26 patients of them eligible for receiving rt-PA (patient group) and 21 patients having contraindications for treatment with rt-PA (control group). Neurological, radiological and laboratory assessment (including BDNF serum level) were done for both groups at stroke onset (before receiving rt-PA) and at day 7. There was a statistically significant increase in BDNF serum level from day 1 to day 7 in rt-PA treated patients in comparison to control group (P-value˂ 0.001). Serum level of BDNF is significantly higher at the onset of stroke in female patients and non-smokers than males or smokers (P-value = 0.011, 0.01 respectively). There was no effect of either age, body mass index, hypertension, diabetes, drug abuse, past or family history of stroke, valvular heart diseases, atrial fibrillation, cardiomyopathy, ejection fraction, carotid atherosclerotic changes, lipid profile or uric acid, on BDNF serum level measured at the onset of stroke. Treatment of patients with acute ischemic stroke with rt-PA causes significant improvement in neuroplasticity through increasing BDNF serum level.

Physiological and neurochemical adaptations following abrupt termination of chronic hypercapnia in goats.

Chronic hypercapnia (CH) is a hallmark of respiratory diseases such as chronic obstructive pulmonary disease. In such patients, mechanical ventilation is often used to restore normal blood-gas homeostasis. However, little is known regarding physiological changes and neuroplasticity within physiological control networks after termination of CH. Utilizing our goat model of increased inspired CO2-induced CH, we determined whether termination of CH elicits time-dependent physiological and neurochemical changes within brain stem sites of physiological control. Thirty days of CH increased [Formula: see text] (+15 mmHg) and steady-state ventilation (SS V̇i; 283% of control). Within 24 h after terminating CH, SS V̇i, blood gases, arterial [H+], and most physiological measurements returned to control. However, the acute ventilatory chemoreflex (ΔV̇i/Δ[H+]) was greater than control, and measured SS V̇i exceeded ventilation predicted by arterial [H+] and ΔV̇i/Δ[H+]. Potentially contributing to these differences were increased excitatory neuromodulators serotonin and norepinephrine in the nucleus tractus solitarius, which contrasts with minimal changes observed at 24 h and 30 days of hypercapnia. Similarly, there were minimal changes found in markers of neuroinflammation and glutamate receptor-dependent neuroplasticity upon termination of CH, which were previously increased following 24 h of hypercapnia. Thus, following termination of CH: 1) ventilatory, renal, and other physiological functions rapidly return to control; 2) neuroplasticity within the ventilatory control network may contribute to the difference between measured vs. predicted ventilation and the elevation in the acute ventilatory [H+] chemoreflex; and 3) neuroplasticity is fundamentally distinct from acclimatization to CH.NEW & NOTEWORTHY In healthy adult goats, steady-state ventilation and most physiological measures return to control within 24 h after termination of chronic hypercapnia (CH). However, the acute [H+] chemoreflex is increased, and measured ventilation exceeds predicted ventilation. At 24 h of recovery, excitatory neuromodulators are above control, but other measured markers of neuroplasticity are unchanged from control. Our data suggest that CH elicits persistent physiological and neurochemical changes for up to 24 h after termination of CH.

Effects of Different High-Intensity Interval Training Regimens on Endurance and Neuroplasticity After Cerebral Ischemia.

The objective is to compare the effects of high-intensity interval training (HIIT) with long versus short intervals on endurance and motor performance. Their influence on neuroplasticity markers is assessed in the ipsilesional and contralesional cortex and hippocampus since their remodeling could improve functional recovery. Rats performed work-matched HIIT4 (long intervals: 4 minutes) or HIIT1 (short intervals: 1 minute) on treadmill for 2 weeks following transient middle cerebral artery occlusion. Forelimb grip strength evaluated motor function while incremental exercise tests measured the endurance performance. Key neuroplasticity markers were assessed by Western blot. Both regimens were effective in enhancing both the speed associated with the lactate threshold and maximal speed at D8 and D15. Neuroplasticity markers were upregulated in the contralesional hemisphere after training contrary to the ipsilesional side. Grip strength completely recovered but is faster with HIIT4. HIIT with short and long intervals induced early aerobic fitness and grip strength improvements. Our findings revealed that neuroplasticity markers were upregulated in the contralesional cortex and hippocampus to promote functional recovery.

Effect of aerobic training on changes in neuroplasticity marker levels in patients with multiple sclerosis – a pilot study

Introduction: Neuroplasticity is the function of the central nervous system that allows structural and functional reorganisation in response to external and internal factors. It is a crucial aspect that allows for the restoration of motor functions in people with limited brain damage. Patients with multiple sclerosis may obtain a special benefit from activities that support brain neuroplasticity. In order to stimulate neuroplasticity, several attempts were made to identify neuroplasticity-influencing factors. Aim: The objective of the study was to measure the effect of aerobic training on plasma neurotrophin levels that are potentially responsible for the brain plasticity phenomenon in patients with multiple sclerosis. Materials and methods: The study was conducted on a group of 22 patients with multiple sclerosis remaining in the drug programs of the National Health Fund. The study group underwent a 4-week rehabilitation scheme that consisted of training on a horizontal ergometer twice a day for 15 minutes 6 days a week, whereas the control group did not participate in any form of training. The plasma levels of neurotrophins (BDNF, PDGF, NGF, GDNF) and fractalkine (chemokine CX3CL1) were tested in all patients, the patients were assessed in the motor disability scale, the cognitive function screening and Beck depression inventory at the beginning of the study and after 4 weeks of rehabilitation. Results: The study showed no statistically significant difference in the levels of neurotrophins assessed before and after 4 weeks of aerobic training. A significant improvement in the clinical condition evaluated with the Expanded Disability Status Scale (EDSS) and Mini-Mental State Examination (MMSE) was observed in patients from the study group. Conclusion: Further studies on larger groups and with more homogenous participants are necessary to gain more insights into this aspect.