Pub Date : 2024-10-20DOI: 10.1016/j.brainres.2024.149288
Aims
The aims were to quantify periventricular and deep white matter hyperintensities (WMHs) in adults with type 1 diabetes with different neuropathic phenotypes and to correlate WMH measurements to explanatory factors in diabetes.
Methods
WMH measurements were obtained from brain magnetic resonance imaging of 56 adults with type 1 diabetes in subgroups including painful diabetic peripheral neuropathy (DPN), painless DPN, without DPN and 20 healthy controls using Fazekas scale and automatic segmentation analysis.
Results
No differences in Fazekas assessed WMHs were found (individuals with periventricular lesions: diabetes 66 % vs. controls 40 %, p = 0.063, deep lesions: diabetes 52 % vs. controls 50 %, p = 1.0). Using automatic detection, there were no significant differences in count of periventricular (p = 0.30) or deep (p = 0.31) WMHs. Higher periventricular lesion burden was present in diabetes compared with controls (0.21 % vs. 0.06 %, p = 0.048), which was associated with more severe DPN, increased age, decreased cognitive function, and reduced volumetric and metabolic brain measures (all p < 0.05).
Conclusions
Our findings indicate increased burden of periventricular WMHs in diabetes which were associated to DPN severity and measurements reflecting neurodegeneration. Deep WMHs, often considered as chronic ischemic, were not significantly different. Mechanisms reflecting neurodegeneration and accelerated brain aging could be an overlooked aspect of peripheral and central neuropathy.
{"title":"Quantification of white matter hyperintensities in type 1 diabetes and its relation to neuropathy and clinical characteristics","authors":"","doi":"10.1016/j.brainres.2024.149288","DOIUrl":"10.1016/j.brainres.2024.149288","url":null,"abstract":"<div><h3>Aims</h3><div>The aims were to quantify periventricular and deep white matter hyperintensities (WMHs) in adults with type 1 diabetes with different neuropathic phenotypes and to correlate WMH measurements to explanatory factors in diabetes.</div></div><div><h3>Methods</h3><div>WMH measurements were obtained from brain magnetic resonance imaging of 56 adults with type 1 diabetes in subgroups including painful diabetic peripheral neuropathy (DPN), painless DPN, without DPN and 20 healthy controls using Fazekas scale and automatic segmentation analysis.</div></div><div><h3>Results</h3><div>No differences in Fazekas assessed WMHs were found (individuals with periventricular lesions: diabetes 66 % vs. controls 40 %, p = 0.063, deep lesions: diabetes 52 % vs. controls 50 %, p = 1.0). Using automatic detection, there were no significant differences in count of periventricular (p = 0.30) or deep (p = 0.31) WMHs. Higher periventricular lesion burden was present in diabetes compared with controls (0.21 % vs. 0.06 %, p = 0.048), which was associated with more severe DPN, increased age, decreased cognitive function, and reduced volumetric and metabolic brain measures (all p < 0.05).</div></div><div><h3>Conclusions</h3><div>Our findings indicate increased burden of periventricular WMHs in diabetes which were associated to DPN severity and measurements reflecting neurodegeneration. Deep WMHs, often considered as chronic ischemic, were not significantly different. Mechanisms reflecting neurodegeneration and accelerated brain aging could be an overlooked aspect of peripheral and central neuropathy.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-20DOI: 10.1016/j.brainres.2024.149287
While molecular adaptations accompanying neuroplasticity during physical exercises are well-established, little is known about adaptations during dysphagia-targeted exercises. This research article has two primary purposes. First, we aim to review the existing literature on the intersection between resistance (strength) training, molecular markers of neuroplasticity, and dysphagia rehabilitation. Specifically, we discuss the molecular mechanisms of two potential molecular markers: brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1) in exercise-induced neuroplasticity. Second, we present preliminary data on the effects of two weeks of detraining on circulating serum BDNF, IGF-1 levels, and expiratory muscle strength. This subset is a part of our more extensive studies related to dysphagia-targeted resistance exercise and neuroplasticity. Five young adult males underwent four weeks of expiratory muscle strength training, followed by two weeks of detraining. We measured expiratory strength, circulating levels of BDNF, and IGF-1 at post-training and detraining conditions. Our results show that expiratory muscle strength, serum BDNF, and IGF-1 levels decreased after detraining; however, this effect was statistically significant only for serum BDNF levels. Oropharyngeal and upper airway musculature involved in swallowing undergoes similar adaptation patterns to skeletal muscles during physical exercise. To fully comprehend the mechanisms underlying the potential neuroplastic benefits of targeted exercise on swallowing functions, mechanistic studies (models) investigating neuroplasticity induced by exercises addressing dysphagia are critical. Such models would ensure that interventions effectively and efficiently achieve neuroplastic benefits and improve patient outcomes, ultimately advancing our understanding of dysphagia-targeted exercise-induced neuroplasticity.
{"title":"Molecular biomarkers of dysphagia targeted exercise induced neuroplasticity: A review of mechanistic processes and preliminary data on detraining effects","authors":"","doi":"10.1016/j.brainres.2024.149287","DOIUrl":"10.1016/j.brainres.2024.149287","url":null,"abstract":"<div><div>While molecular adaptations accompanying neuroplasticity during physical exercises are well-established, little is known about adaptations during dysphagia-targeted exercises. This research article has two primary purposes. First, we aim to review the existing literature on the intersection between resistance (strength) training, molecular markers of neuroplasticity, and dysphagia rehabilitation. Specifically, we discuss the molecular mechanisms of two potential molecular markers: brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1) in exercise-induced neuroplasticity. Second, we present preliminary data on the effects of two weeks of detraining on circulating serum BDNF, IGF-1 levels, and expiratory muscle strength. This subset is a part of our more extensive studies related to dysphagia-targeted resistance exercise and neuroplasticity. Five young adult males underwent four weeks of expiratory muscle strength training, followed by two weeks of detraining. We measured expiratory strength, circulating levels of BDNF, and IGF-1 at post-training and detraining conditions. Our results show that expiratory muscle strength, serum BDNF, and IGF-1 levels decreased after detraining; however, this effect was statistically significant only for serum BDNF levels. Oropharyngeal and upper airway musculature involved in swallowing undergoes similar adaptation patterns to skeletal muscles during physical exercise. To fully comprehend the mechanisms underlying the potential neuroplastic benefits of targeted exercise on swallowing functions, mechanistic studies (models) investigating neuroplasticity induced by exercises addressing dysphagia are critical. Such models would ensure that interventions effectively and efficiently achieve neuroplastic benefits and improve patient outcomes, ultimately advancing our understanding of dysphagia-targeted exercise-induced neuroplasticity.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-20DOI: 10.1016/j.brainres.2024.149286
Post-traumatic stress disorder (PTSD) is a severe mental illness that could impose heavy burdens on individuals and society, but effective and precise treatment modalities are unknown. The level of hydrogen sulfide (H2S) in the brain plays an important role in psychiatric diseases. However, it is still unclear whether PTSD exposure could affect the level of H2S and whether there is a correlation between H2S levels and the pathogenesis of PTSD. In this study, we selected single prolonged stress (SPS) as a PTSD model and found that SPS exposure decreased the endogenous H2S content accompanied by abnormal behavioral changes and dysregulation of the hippocampal synaptic plasticity in SPS rats. We further found that the exogenous administration of H2S could alleviate PTSD-like behaviors and improve hippocampal synaptic plasticity in SPS rats. In addition, we further used the phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002 to interfere with the PI3K/AKT/BDNF signaling pathway. It was found that LY294002 significantly blocked the anti-anxiety effect and the improvement in synaptic plasticity derived from the exogenous administration of H2S in SPS rats. These results suggested that the endogenous H2S content was decreased in SPS rats, and that the exogenous administration of H2S could ameliorate abnormal disorders and improve hippocampal synaptic plasticity by mediating the PI3K/AKT pathway.
{"title":"H2S improves hippocampal synaptic plasticity in SPS rats via PI3K/AKT signaling pathway","authors":"","doi":"10.1016/j.brainres.2024.149286","DOIUrl":"10.1016/j.brainres.2024.149286","url":null,"abstract":"<div><div>Post-traumatic stress disorder (PTSD) is a severe mental illness that could impose heavy burdens on individuals and society, but effective and precise treatment modalities are unknown. The level of hydrogen sulfide (H<sub>2</sub>S) in the brain plays an important role in psychiatric diseases. However, it is still unclear whether PTSD exposure could affect the level of H<sub>2</sub>S and whether there is a correlation between H<sub>2</sub>S levels and the pathogenesis of PTSD. In this study, we selected single prolonged stress (SPS) as a PTSD model and found that SPS exposure decreased the endogenous H<sub>2</sub>S content accompanied by abnormal behavioral changes and dysregulation of the hippocampal synaptic plasticity in SPS rats. We further found that the exogenous administration of H<sub>2</sub>S could alleviate PTSD-like behaviors and improve hippocampal synaptic plasticity in SPS rats. In addition, we further used the phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002 to interfere with the PI3K/AKT/BDNF signaling pathway. It was found that LY294002 significantly blocked the anti-anxiety effect and the improvement in synaptic plasticity derived from the exogenous administration of H<sub>2</sub>S in SPS rats. These results suggested that the endogenous H<sub>2</sub>S content was decreased in SPS rats, and that the exogenous administration of H<sub>2</sub>S could ameliorate abnormal disorders and improve hippocampal synaptic plasticity by mediating the PI3K/AKT pathway.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-18DOI: 10.1016/j.brainres.2024.149283
<div><div>Alzheimer’s disease (AD), the most prevalent human dementia, is driven by accruals of extracellular Aβ<sub>42</sub> senile patches and intracellular neurofibrillary tangles of hyperphosphorylated Tau (p-Tau) proteins. AD’s concurrent neuroinflammation is prompted by innate immunity-related cytosolic protein oligomers named inflammasomes. Upon proper “first” (priming) and “second” (activating) signals, inflammasomes overproduce proinflammatory Interleukin (IL)-1β, and IL-18 while cleaving pyroptosis-promoting Gasdermin D’s N-terminal fragments. Our earlier studies highlighted that in pure monocultures, exogenous Aβ<sub>25-35</sub>-treated nonproliferating human cortical astrocytes (HCAs) made and released surpluses of endogenous Aβ<sub>42</sub>-oligomers (−os) and p-Tau-os, just as alike-treated human cortical neurons did. Aβ<sub>25-35</sub>-exposed HCAs also over-released NO, VEGFA, and IL-6. Aβ•CaSR (Aβ·Calcium-Sensing Receptor) complexes generated intracellular signals mediating all such neurotoxic effects since CaSR’s negative allosteric modulators (aka NAMs or calcilytics, e.g., NPS2143) fully suppressed them. However, it had hitherto remained unexplored whether signals from Aβ·CaSR complexes also induced the early expression and/or activation of NOD-like 2 (NLRP2) and 3 (NLRP3) and of PYHIN absent in melanoma 2 (AIM2) inflammasomes in monocultured HCAs. To clarify this topic, we used <em>in-situ</em>-Proximity Ligation, qRT-PCR, double antibody arrays, immunoblots, and Caspase 1/4 enzymatic assays. Aβ·CaSR complexes quickly assembled on HCAs surface and issued intracellular signals activating Akt and JAK/STAT axes. In turn, the latter upregulated NLRP2 and NLRP3 PRRs (pattern recognition receptors) yet downregulated AIM2. These effects were specific, being significantly hindered by NPS2143 and inhibitors of PI3K (LY294002), AMPKα (Dorsomorphin), mTOR (Torin1), and JAK/TYK (Brepoticinib). A wide-spectrum inhibitor, Bay11-7082, intensified the Aβ·CaSR/Akt/JAK/STAT axis-driven opposite control of NLRP3’s and AIM2’s PRR proteins without affecting NLRP2 PRR upregulation. However, the said effects on the PRRs proteins vanished within 24-h. Moreover, Aβ·CaSR signals neither concurrently changed ASC, pro-IL-1β, and Gasdermin-D (holo- and fragments) protein levels and Caspases 1 and 4 enzymatic activities nor induced pyroptosis. Therefore, Aβ·CaSR cues acted as “first (priming) signals” temporarily increasing NLRP2 and NLRP3 PRRs expression without activating the corresponding inflammasomes. The neatly divergent modulation of NLRP3’s <em>vs</em>. AIM2’s PRR proteins by Aβ·CaSR cues and by Bay11-7082 suggests that, when bacterial or viral DNA fragments are absent, AIM2 might play “anti-inflammasomal” or other roles in HCAs. However, Bay11-7082’s no effect on NLRP2 PRR overexpression also reveals that CaSR’s downstream mechanisms controlling inflammasomes’ sensors are quite complex in HCAs, and hence, given AD’s impact on human health, well w
{"title":"Early divergent modulation of NLRP2′s and NLRP3′s inflammasome sensors vs. AIM2′s one by signals from Aβ·Calcium-sensing receptor complexes in human astrocytes","authors":"","doi":"10.1016/j.brainres.2024.149283","DOIUrl":"10.1016/j.brainres.2024.149283","url":null,"abstract":"<div><div>Alzheimer’s disease (AD), the most prevalent human dementia, is driven by accruals of extracellular Aβ<sub>42</sub> senile patches and intracellular neurofibrillary tangles of hyperphosphorylated Tau (p-Tau) proteins. AD’s concurrent neuroinflammation is prompted by innate immunity-related cytosolic protein oligomers named inflammasomes. Upon proper “first” (priming) and “second” (activating) signals, inflammasomes overproduce proinflammatory Interleukin (IL)-1β, and IL-18 while cleaving pyroptosis-promoting Gasdermin D’s N-terminal fragments. Our earlier studies highlighted that in pure monocultures, exogenous Aβ<sub>25-35</sub>-treated nonproliferating human cortical astrocytes (HCAs) made and released surpluses of endogenous Aβ<sub>42</sub>-oligomers (−os) and p-Tau-os, just as alike-treated human cortical neurons did. Aβ<sub>25-35</sub>-exposed HCAs also over-released NO, VEGFA, and IL-6. Aβ•CaSR (Aβ·Calcium-Sensing Receptor) complexes generated intracellular signals mediating all such neurotoxic effects since CaSR’s negative allosteric modulators (aka NAMs or calcilytics, e.g., NPS2143) fully suppressed them. However, it had hitherto remained unexplored whether signals from Aβ·CaSR complexes also induced the early expression and/or activation of NOD-like 2 (NLRP2) and 3 (NLRP3) and of PYHIN absent in melanoma 2 (AIM2) inflammasomes in monocultured HCAs. To clarify this topic, we used <em>in-situ</em>-Proximity Ligation, qRT-PCR, double antibody arrays, immunoblots, and Caspase 1/4 enzymatic assays. Aβ·CaSR complexes quickly assembled on HCAs surface and issued intracellular signals activating Akt and JAK/STAT axes. In turn, the latter upregulated NLRP2 and NLRP3 PRRs (pattern recognition receptors) yet downregulated AIM2. These effects were specific, being significantly hindered by NPS2143 and inhibitors of PI3K (LY294002), AMPKα (Dorsomorphin), mTOR (Torin1), and JAK/TYK (Brepoticinib). A wide-spectrum inhibitor, Bay11-7082, intensified the Aβ·CaSR/Akt/JAK/STAT axis-driven opposite control of NLRP3’s and AIM2’s PRR proteins without affecting NLRP2 PRR upregulation. However, the said effects on the PRRs proteins vanished within 24-h. Moreover, Aβ·CaSR signals neither concurrently changed ASC, pro-IL-1β, and Gasdermin-D (holo- and fragments) protein levels and Caspases 1 and 4 enzymatic activities nor induced pyroptosis. Therefore, Aβ·CaSR cues acted as “first (priming) signals” temporarily increasing NLRP2 and NLRP3 PRRs expression without activating the corresponding inflammasomes. The neatly divergent modulation of NLRP3’s <em>vs</em>. AIM2’s PRR proteins by Aβ·CaSR cues and by Bay11-7082 suggests that, when bacterial or viral DNA fragments are absent, AIM2 might play “anti-inflammasomal” or other roles in HCAs. However, Bay11-7082’s no effect on NLRP2 PRR overexpression also reveals that CaSR’s downstream mechanisms controlling inflammasomes’ sensors are quite complex in HCAs, and hence, given AD’s impact on human health, well w","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-17DOI: 10.1016/j.brainres.2024.149282
Background
First-episode antipsychotics-naïve schizophrenia (FEAN-SCZ) is associated with abnormalities in glucose and lipid metabolism. While sex differences in the incidence and severity of SCZ and metabolic abnormalities have been documented, the specific metabolic abnormalities between the sexes remain unclear. The study aimed to investigate sex-specific differences in plasma glycolipid profiles in FEAN-SCZ patients.
Methods
A total of 172 FEAN-SCZ patients (male/female: 83/89) and 31 healthy controls (male/female: 14/17) were recruited. Psychopathology assessment was conducted using the Positive and Negative Syndrome Scale (PANSS). Glycolipid profiles, including oral glucose tolerance test (OGTT), fasting glucose, insulin, total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) were examined in all participants.
Results
FEAN patients displayed significantly higher fasting and 2-hour glucose levels compared to healthy controls (both p < 0.001). Impaired glucose tolerance (IGT) prevalence in male patients was 24.1 % (n = 20) and 25.9 % (n = 23) in females, contrasting with 0 % (n = 0) in the control group. FEAN patients exhibited elevated blood insulin and TC levels (both p < 0.05) and increased insulin resistance measured by HOMA-IR (p < 0.01). Among male patients, those with IGT had significantly higher TC, TG and LDL levels than non-IGT patients (all p < 0.05), while no significant differences were observed in female patients between IGT and non-IGT groups. Body mass index (BMI), TG and HDL levels were identified as significant predictors of IGT in male FEAN patients.
Conclusions
IGT is present in a subset of FEAN-SCZ patients. Male patients with IGT exhibit distinct alterations in plasma lipid profiles compared to non-IGT patients.
{"title":"Sex differences in plasma lipid profiles, but not in glucose metabolism in patients with first-episode antipsychotics-naïve schizophrenia","authors":"","doi":"10.1016/j.brainres.2024.149282","DOIUrl":"10.1016/j.brainres.2024.149282","url":null,"abstract":"<div><h3>Background</h3><div>First-episode antipsychotics-naïve schizophrenia (FEAN-SCZ) is associated with abnormalities in glucose and lipid metabolism. While sex differences in the incidence and severity of SCZ and metabolic abnormalities have been documented, the specific metabolic abnormalities between the sexes remain unclear. The study aimed to investigate sex-specific differences in plasma glycolipid profiles in FEAN-SCZ patients.</div></div><div><h3>Methods</h3><div>A total of 172 FEAN-SCZ patients (male/female: 83/89) and 31 healthy controls (male/female: 14/17) were recruited. Psychopathology assessment was conducted using the Positive and Negative Syndrome Scale (PANSS). Glycolipid profiles, including oral glucose tolerance test (OGTT), fasting glucose, insulin, total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) were examined in all participants.</div></div><div><h3>Results</h3><div>FEAN patients displayed significantly higher fasting and 2-hour glucose levels compared to healthy controls (both <em>p</em> < 0.001). Impaired glucose tolerance (IGT) prevalence in male patients was 24.1 % (n = 20) and 25.9 % (n = 23) in females, contrasting with 0 % (n = 0) in the control group. FEAN patients exhibited elevated blood insulin and TC levels (both <em>p</em> < 0.05) and increased insulin resistance measured by HOMA-IR (<em>p</em> < 0.01). Among male patients, those with IGT had significantly higher TC, TG and LDL levels than non-IGT patients (all <em>p</em> < 0.05), while no significant differences were observed in female patients between IGT and non-IGT groups. Body mass index (BMI), TG and HDL levels were identified as significant predictors of IGT in male FEAN patients.</div></div><div><h3>Conclusions</h3><div>IGT is present in a subset of FEAN-SCZ patients. Male patients with IGT exhibit distinct alterations in plasma lipid profiles compared to non-IGT patients.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-17DOI: 10.1016/j.brainres.2024.149260
Introduction
The investigation of brainwave changes during the recovery process of unilateral spatial neglect (USN) has garnered considerable attention in recent years. This paper presents an updated overview of the evolving brainwave patterns during USN rehabilitation, aiming to predict clinical outcomes and guide the selection of effective recovery strategies.
Methods
A systematic review was conducted, encompassing English literature published up to June 2024. Databases including PubMed, Web of Science, and clinical trials were utilized. The included studies assessed brainwaves using electroencephalography (EEG) in at least one group with USN. However, the diverse nature of these studies posed challenges for a quantitative synthesis.
Results
The final quantitative synthesis comprised 36 studies, incorporating a total of 4517 data points. The analysis revealed abnormalities in alpha, beta, and gamma brainwave activity, along with alterations in the functional monitoring of the alpha band during USN rehabilitation. Additionally, reductions were observed in specific brainwave components such as P1, N1, P2, P300, early directing attention negativity (EDAN), late directing attention positivity (LDAP), and contingent negative variation (CNV). However, findings regarding measures of synchrony, connectivity, and evoked responses across different frequency bands exhibited variability.
Conclusions
Various indicators of brainwave activity displayed changes at different stages of post-stroke neglect rehabilitation, highlighting the significance of neural network dysfunction in this process. Nonetheless, due to the diversity of the studies, further investigation is necessary to achieve a more comprehensive understanding in future research endeavors.
{"title":"Electrophysiological measures of patients with unilateral spatial neglect after brain disease: A systematic review","authors":"","doi":"10.1016/j.brainres.2024.149260","DOIUrl":"10.1016/j.brainres.2024.149260","url":null,"abstract":"<div><h3>Introduction</h3><div>The investigation of brainwave changes during the recovery process of unilateral spatial neglect (USN) has garnered considerable attention in recent years. This paper presents an updated overview of the evolving brainwave patterns during USN rehabilitation, aiming to predict clinical outcomes and guide the selection of effective recovery strategies.</div></div><div><h3>Methods</h3><div>A systematic review was conducted, encompassing English literature published up to June 2024. Databases including PubMed, Web of Science, and clinical trials were utilized. The included studies assessed brainwaves using electroencephalography (EEG) in at least one group with USN. However, the diverse nature of these studies posed challenges for a quantitative synthesis.</div></div><div><h3>Results</h3><div>The final quantitative synthesis comprised 36 studies, incorporating a total of 4517 data points. The analysis revealed abnormalities in alpha, beta, and gamma brainwave activity, along with alterations in the functional monitoring of the alpha band during USN rehabilitation. Additionally, reductions were observed in specific brainwave components such as P1, N1, P2, P300, early directing attention negativity (EDAN), late directing attention positivity (LDAP), and contingent negative variation (CNV). However, findings regarding measures of synchrony, connectivity, and evoked responses across different frequency bands exhibited variability.</div></div><div><h3>Conclusions</h3><div>Various indicators of brainwave activity displayed changes at different stages of post-stroke neglect rehabilitation, highlighting the significance of neural network dysfunction in this process. Nonetheless, due to the diversity of the studies, further investigation is necessary to achieve a more comprehensive understanding in future research endeavors.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.1016/j.brainres.2024.149280
Alzheimer’s Disease (AD) is the primary neurodegenerative disorder in the elderly, lacking a definitive treatment. The gut microbiota influences the gut-brain axis by aiding in hypothalamic–pituitary–adrenal (HPA) axis development and neuromodulator production. Research links AD and gut microbiota, suggesting gut microbiota regulation could be a therapeutic approach for AD. This study explores Akkermansia muciniphila’s impact on preventing AD. This research investigates the effect of A. muciniphila consumption (1 × 109 CFU) on tau protein-induced AD rats compared to a control group. Rats were divided into four groups: sham, sham + Akk, AD (tau-induced rats), and AD + Akk (tau-induced rats treated with A. muciniphila). A. muciniphila gavage lasted five weeks. Rats underwent qRT-PCR analysis to assess mRNA expression of pro-inflammatory factors (TNF-α, IL-6, IL-1β, IFN-γ) in the hippocampus. Behavioral tests included Morris Water Maze (MWM), Passive Avoidance Memory Test (Shuttle box), Elevated Plus Maze (EPM), and marble burying. After five weeks of A. muciniphila treatment, anxiety-like behavior significantly decreased. The AD group receiving A. muciniphila showed improved spatial and recognition memory compared to the AD group. Pro-inflammatory cytokine levels (TNF-α, IL-1β, IL-6, IFN-γ) decreased. A. muciniphila effectively reduces cognitive impairments and anxiety-related behavior, showing promise as an AD therapeutic by influencing the gut-brain axis.
阿尔茨海默病（AD）是老年人主要的神经退行性疾病，目前尚无确切的治疗方法。肠道微生物群通过帮助下丘脑-垂体-肾上腺（HPA）轴的发育和神经调节剂的产生来影响肠道-大脑轴。研究将注意力缺失症与肠道微生物群联系起来，表明肠道微生物群调节可能是注意力缺失症的一种治疗方法。本研究探讨了 Akkermansia muciniphila 对预防注意力缺失症的影响。与对照组相比，本研究调查了食用 A. muciniphila（1 × 109 CFU）对 tau 蛋白诱导的 AD 大鼠的影响。大鼠被分为四组：假组、假+Akk组、AD组（tau诱导的大鼠）和AD+Akk组（用粘蛋白噬菌体治疗tau诱导的大鼠）。灌胃 A. muciniphila 持续五周。对大鼠进行qRT-PCR分析，以评估海马中促炎因子（TNF-α、IL-6、IL-1β、IFN-γ）的mRNA表达。行为测试包括莫里斯水迷宫（MWM）、被动回避记忆测试（穿梭箱）、高架正迷宫（EPM）和大理石埋藏。经过五周的A. muciniphila治疗后，焦虑样行为明显减少。与AD组相比，接受A. muciniphila治疗的AD组的空间记忆和识别记忆有所改善。促炎细胞因子水平（TNF-α、IL-1β、IL-6、IFN-γ）下降。A.muciniphila能有效减少认知障碍和焦虑相关行为，通过影响肠道-大脑轴，有望成为一种AD疗法。
{"title":"Ameliorative effects of Akkermansia muciniphila on anxiety-like behavior and cognitive deficits in a rat model of Alzheimer’s disease","authors":"","doi":"10.1016/j.brainres.2024.149280","DOIUrl":"10.1016/j.brainres.2024.149280","url":null,"abstract":"<div><div>Alzheimer’s Disease (AD) is the primary neurodegenerative disorder in the elderly, lacking a definitive treatment. The gut microbiota influences the gut-brain axis by aiding in hypothalamic–pituitary–adrenal (HPA) axis development and neuromodulator production. Research links AD and gut microbiota, suggesting gut microbiota regulation could be a therapeutic approach for AD. This study explores <em>Akkermansia muciniphila</em>’s impact on preventing AD. This research investigates the effect of <em>A. muciniphila</em> consumption (1 × 10<sup>9</sup> CFU) on tau protein-induced AD rats compared to a control group. Rats were divided into four groups: sham, sham + Akk, AD (tau-induced rats), and AD + Akk (tau-induced rats treated with <em>A. muciniphila</em>). <em>A. muciniphila</em> gavage lasted five weeks. Rats underwent qRT-PCR analysis to assess mRNA expression of pro-inflammatory factors (<em>TNF-α</em>, <em>IL-6</em>, <em>IL-1β</em>, <em>IFN-γ</em>) in the hippocampus. Behavioral tests included Morris Water Maze (MWM), Passive Avoidance Memory Test (Shuttle box), Elevated Plus Maze (EPM), and marble burying. After five weeks of <em>A. muciniphila</em> treatment, anxiety-like behavior significantly decreased. The AD group receiving <em>A. muciniphila</em> showed improved spatial and recognition memory compared to the AD group. Pro-inflammatory cytokine levels (<em>TNF-α</em>, <em>IL-1β</em>, <em>IL-6</em>, <em>IFN-γ</em>) decreased. <em>A. muciniphila</em> effectively reduces cognitive impairments and anxiety-related behavior, showing promise as an AD therapeutic by influencing the gut-brain axis.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.1016/j.brainres.2024.149281
Environmental enrichment (EE) consists of increased living space, complex stimuli, and social interaction that collectively confer neurobehavioral benefits in preclinical models of traumatic brain injury (TBI). The typical EE approach entails implementation immediately after surgery and continual exposure, which is not clinically applicable, as TBI patients often only receive rehabilitation after critical care, and then only for a few hours per day. We are focused on developing a clinically relevant model of neurorehabilitation by refining the timing of initiation and duration of EE exposure after TBI. The goal of this experiment is to compare the typical EE approach to paradigms where EE is delayed by 3 or 7 days after TBI and then provided for only 6 h per day, which better mimics the clinic. The hypothesis is that the delayed-and-abbreviated EE paradigms will promote neurobehavioral benefits like the typical approach of immediate-and-continuous exposure. To test the hypothesis, anesthetized adult male rats underwent a controlled cortical impact of moderate severity (2.8 mm deformation at 4 m/s) or sham injury and then were randomly assigned to post-operative EE or standard (STD) housing. Motor ability, spatial learning, and memory retention were assessed. The hypothesis was confirmed as all EE-treated groups performed better than the STD group in all behavioral assessments (p < 0.05) and did not differ from one another (p > 0.05). The ability of EE to provide significant behavioral benefits even when delayed and delivered in moderation affords further support for EE as a preclinical model of neurorehabilitation and offers greater insight into the length of the therapeutic window.
丰富环境（EE）包括增加生活空间、复杂刺激和社交互动，这些因素共同为创伤性脑损伤（TBI）临床前模型的神经行为带来益处。典型的 EE 方法需要在手术后立即实施并持续暴露于环境中，这在临床上并不适用，因为创伤性脑损伤患者通常只能在重症监护后接受康复治疗，而且每天只能接受几个小时的康复治疗。我们的重点是通过改进创伤性脑损伤后开始 EE 的时间和持续时间，开发一种与临床相关的神经康复模式。本实验的目的是将典型的 EE 方法与延迟 3 天或 7 天，然后每天只提供 6 小时 EE 的范例进行比较，后者更能模拟临床。我们的假设是，延迟和简短的 EE 范例将促进神经行为的益处，就像典型的立即和持续暴露的方法一样。为了验证这一假设，麻醉后的成年雄性大鼠接受了中等严重程度（2.8 毫米变形，4 米/秒）的受控皮层冲击或假性损伤，然后被随机分配到术后 EE 或标准（STD）饲养室。对运动能力、空间学习能力和记忆保持能力进行了评估。假设得到了证实，所有 EE 治疗组在所有行为评估中的表现均优于 STD 组（P 0.05）。EE 即使在延迟和适度给药的情况下也能带来显著的行为益处，这进一步支持了将 EE 作为神经康复的临床前模型，并使人们对治疗窗口期的长度有了更深入的了解。
{"title":"Delayed-and-abbreviated environmental enrichment after traumatic brain injury confers neurobehavioral benefits similar to immediate-and-continuous exposure","authors":"","doi":"10.1016/j.brainres.2024.149281","DOIUrl":"10.1016/j.brainres.2024.149281","url":null,"abstract":"<div><div>Environmental enrichment (EE) consists of increased living space, complex stimuli, and social interaction that collectively confer neurobehavioral benefits in preclinical models of traumatic brain injury (TBI). The typical EE approach entails implementation immediately after surgery and continual exposure, which is not clinically applicable, as TBI patients often only receive rehabilitation after critical care, and then only for a few hours per day. We are focused on developing a clinically relevant model of neurorehabilitation by refining the timing of initiation and duration of EE exposure after TBI. The goal of this experiment is to compare the typical EE approach to paradigms where EE is delayed by 3 or 7 days after TBI and then provided for only 6 h per day, which better mimics the clinic. The hypothesis is that the delayed-and-abbreviated EE paradigms will promote neurobehavioral benefits like the typical approach of immediate-and-continuous exposure. To test the hypothesis, anesthetized adult male rats underwent a controlled cortical impact of moderate severity (2.8 mm deformation at 4 m/s) or sham injury and then were randomly assigned to post-operative EE or standard (STD) housing. Motor ability, spatial learning, and memory retention were assessed. The hypothesis was confirmed as all EE-treated groups performed better than the STD group in all behavioral assessments (<em>p</em> < 0.05) and did not differ from one another (<em>p</em> > 0.05). The ability of EE to provide significant behavioral benefits even when delayed and delivered in moderation affords further support for EE as a preclinical model of neurorehabilitation and offers greater insight into the length of the therapeutic window.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16DOI: 10.1016/j.brainres.2024.149284
Background and purpose
The intricate roles of NMDA receptors, specifically those containing the NR2A or NR2B subunit, in ischemic stroke pathology necessitate targeted therapeutic investigations. Building on our prior discovery showcasing the neuroprotective potential of 2-(benzofuran-2-yl)-2-imidazoline (2-BFI), an imidazoline I2 receptor ligand, in inhibiting NMDA receptor currents during ischemic stroke, this study aims to elucidate the specific impact of 2-BFI on NR2A- and NR2B-containing NMDARs.
Experimental approach
Through whole-cell patch-clamp techniques, we observed an inhibition by 2-BFI on NR2A-containing NMDAR currents (IC50 = 238.6 μM) and NR2B-containing NMDAR currents (IC50 = 18.47 μM). Experiments with HEK293 cells expressing exogenous receptor subunits revealed a significantly higher affinity of 2-BFI towards NR2B-containing NMDARs. In vivo studies involved the co-administration of 2-BFI and the NR2A subunit antagonist NVP-AAM077 in rats subjected to transient middle cerebral artery occlusion (tMCAO).
Key results
2-BFI exhibited a pronounced preference for inhibiting NR2B-containing NMDAR currents, leading to a notable mitigation of cerebral ischemic injury when administered in conjunction with NVP-AAM077 in the tMCAO rat model. Furthermore, alterations in the expression of downstream proteins specific to NR2B-containing NMDA receptors were observed, suggesting targeted molecular effects.
Conclusion and implications
This study unveils the neuroprotective potential of 2-BFI in ischemic stroke by selectively inhibiting NR2B-containing NMDA receptors. These findings lay the foundation for precise therapeutic strategies, showcasing the differential roles of NR2A and NR2B subunits and paving the way for advancements in targeted interventions for ischemic stroke treatment.
{"title":"2-BFI protects against ischemic stroke by selectively acting on NR2B-containing NMDA receptors","authors":"","doi":"10.1016/j.brainres.2024.149284","DOIUrl":"10.1016/j.brainres.2024.149284","url":null,"abstract":"<div><h3>Background and purpose</h3><div>The intricate roles of NMDA receptors, specifically those containing the NR2A or NR2B subunit, in ischemic stroke pathology necessitate targeted therapeutic investigations. Building on our prior discovery showcasing the neuroprotective potential of 2-(benzofuran-2-yl)-2-imidazoline (2-BFI), an imidazoline I2 receptor ligand, in inhibiting NMDA receptor currents during ischemic stroke, this study aims to elucidate the specific impact of 2-BFI on NR2A- and NR2B-containing NMDARs.</div></div><div><h3>Experimental approach</h3><div>Through whole-cell patch-clamp techniques, we observed an inhibition by 2-BFI on NR2A-containing NMDAR currents (IC50 = 238.6 μM) and NR2B-containing NMDAR currents (IC50 = 18.47 μM). Experiments with HEK293 cells expressing exogenous receptor subunits revealed a significantly higher affinity of 2-BFI towards NR2B-containing NMDARs. In vivo studies involved the co-administration of 2-BFI and the NR2A subunit antagonist NVP-AAM077 in rats subjected to transient middle cerebral artery occlusion (tMCAO).</div><div>Key results</div><div>2-BFI exhibited a pronounced preference for inhibiting NR2B-containing NMDAR currents, leading to a notable mitigation of cerebral ischemic injury when administered in conjunction with NVP-AAM077 in the tMCAO rat model. Furthermore, alterations in the expression of downstream proteins specific to NR2B-containing NMDA receptors were observed, suggesting targeted molecular effects.</div><div>Conclusion and implications</div><div>This study unveils the neuroprotective potential of 2-BFI in ischemic stroke by selectively inhibiting NR2B-containing NMDA receptors. These findings lay the foundation for precise therapeutic strategies, showcasing the differential roles of NR2A and NR2B subunits and paving the way for advancements in targeted interventions for ischemic stroke treatment.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14DOI: 10.1016/j.brainres.2024.149278
A close correlation exists between the macrophage/microglia(MΦ/MG) polarization states and the development of cerebral ischemia and reperfusion (I/R). Therefore it is of great significance to research on how to modulate the MΦ/MG states for improved patient outcomes. In particular, regulatory mechanisms involved in this process remain to be identified. Hereby, we aim to shed light on how docosahexaenoic acid (DHA) actively modulates the switch between M1 and M2 macrophage states by restraining the NACHT-LRR-PYD-containing protein three inflammasome (NALP3). We found that NALP3-positive cells were detected in clinical human cerebral infarction tissue samples and the mouse tMCAO model. In mice after DHA treatment, the number of NALP3-positive cells was significantly reduced, significantly decreasing infarct volume and improving the postoperative physical status of mice. NALP3-positive cells were found to be MΦ/MG after co-staining with CD11b. By extracting peritoneal macrophages, it was verified that DHA inhibited the activation of NALP3 and regulated the transformation of M1 and M2 cells, thereby reducing I/R injury.
巨噬细胞/小胶质细胞（MΦ/MG）的极化状态与脑缺血和再灌注（I/R）的发生密切相关。因此，研究如何调节 MΦ/MG 状态以改善患者预后具有重要意义。特别是，参与这一过程的调控机制仍有待确定。在此，我们旨在揭示二十二碳六烯酸（DHA）如何通过抑制含NACHT-LRR-PYD蛋白的三炎症小体（NALP3）来积极调节M1和M2巨噬细胞状态之间的转换。我们发现，在临床人类脑梗塞组织样本和小鼠 tMCAO 模型中都检测到了 NALP3 阳性细胞。小鼠经 DHA 治疗后，NALP3 阳性细胞的数量明显减少，梗死体积明显缩小，术后身体状况明显改善。NALP3阳性细胞与CD11b共染后发现是MΦ/MG。通过提取腹腔巨噬细胞，验证了 DHA 可抑制 NALP3 的活化，调节 M1 和 M2 细胞的转化，从而减轻 I/R 损伤。
{"title":"DHA plays a protective role in cerebral ischemia–reperfusion injury by affecting macrophage/microglia type polarization","authors":"","doi":"10.1016/j.brainres.2024.149278","DOIUrl":"10.1016/j.brainres.2024.149278","url":null,"abstract":"<div><div>A close correlation exists between the macrophage/microglia(MΦ/MG) polarization states and the development of cerebral ischemia and reperfusion (I/R). Therefore it is of great significance to research on how to modulate the MΦ/MG states for improved patient outcomes. In particular, regulatory mechanisms involved in this process remain to be identified. Hereby, we aim to shed light on how docosahexaenoic acid (DHA) actively modulates the switch between M1 and M2 macrophage states by restraining the NACHT-LRR-PYD-containing protein three inflammasome (NALP3). We found that NALP3-positive cells were detected in clinical human cerebral infarction tissue samples and the mouse tMCAO model. In mice after DHA treatment, the number of NALP3-positive cells was significantly reduced, significantly decreasing infarct volume and improving the postoperative physical status of mice. NALP3-positive cells were found to be MΦ/MG after co-staining with CD11b. By extracting peritoneal macrophages, it was verified that DHA inhibited the activation of NALP3 and regulated the transformation of M1 and M2 cells, thereby reducing I/R injury.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号