Recovery Of Brain Function Research Articles

Neuronutrition and Its Impact on Post-Stroke Neurorehabilitation: Modulating Plasticity Through Diet

The recovery of neurological deficits after ischemic stroke largely depends on the brain’s ability to reorganize its undamaged neuronal circuits and neuronal plasticity phenomena. The consolidated evidence highlights the involvement of the patient’s impaired nutritional conditions in post-stroke recovery and unsatisfying rehabilitative outcomes. Standardized nutritional protocols usually applied in hospitalized patients in a rehabilitation setting aim mainly to improve the general health conditions of patients, do not consider the high inter-individual variability in neurorehabilitation outcomes, and are not sufficiently modifiable to provide neuroprotective and restorative dietary patterns that could promote neuronal plasticity and functional recovery during neurorehabilitation. Neuronutrition, an emergent scientific field of neuroscience, represents a valid model of a personalized nutritional approach, assuring, for each patient, nutrients having antioxidant and anti-inflammatory properties, ensuring a balanced microbiota composition, and providing adequate neurotrophic support, essential for improving neuronal plasticity, brain functional recovery, and rehabilitative outcomes. In the present narrative review, we provide an overview of the current knowledge on neuronutrition as an adjuvant strategy of a personalized nutritional approach potentially effective in improving post-stroke neuroplasticity and neurorehabilitation by counteracting or at least limiting post-stroke oxidative/nitrosative stress, neuroinflammation, and gut–brain axis disturbance.

Exploring the Impact of Cognitive Dysfunction During Recurrent Depression in a Sample of Mid-to-Older Age British South Asians: A Qualitative Study.

Depression is a major public health issue, increasing the risk of comorbidities. Some people with depression experience cognitive dysfunction, which can persist even after symptomatic recovery. British South Asians are at greater risk of developing depression and are less likely to seek treatment. It is important to understand their experience of subjective cognitive dysfunction in depression and how best to support them. This study explored subjective experience of cognitive dysfunction during recurrent depression, in a sample of 12 British South Asians aged between 45 and 60 years. We conducted semi-structured interviews to explore cognitive dysfunction during recurrent depression. We analysed the data using thematic analysis. Difficulties in attention and concentration resulted in lower quality of social relationships, including not feeling present and social isolation. Learning new information was difficult, thus impacting productivity. Participants found it difficult to engage in enjoyable activities that promoted brain health. The emotional, physical and spiritual impact negatively impacted on quality of life. Cognitive strategies used in therapies could improve brain health and functional recovery in people living with depression. Mental health nurses play a pivotal role in providing culturally appropriate information and strategies for managing cognitive dysfunction in recurrent depression.

The Role of Osteopontin (OPN) in Regulating Microglia Phagocytosis in Nervous System Diseases.

Phagocytosis is the process by which certain cells or organelles internalise foreign substances by engulfing them and then digesting or disposing of them. Microglia are the main resident phagocytic cells in the brain. It is generally believed that microglia/macrophages play a role in guiding the brain's repair and functional recovery processes. However, the resident and invading immune cells of the central nervous system can also exacerbate tissue damage by stimulating inflammation and engulfing viable neurons. The functional consequences of microglial phagocytosis remain largely unexplored. Overall, phagocytosis is considered a beneficial phenomenon in acute brain injury because it eliminates dead cells and induces an anti-inflammatory response. Osteopontin (OPN) is a phosphorylated glycoprotein induced by injury in various tissues, including brain tissue. In acute brain injuries such as hemorrhagic stroke and ischemic stroke, OPN is generally believed to have anti-inflammatory effects. OPN can promote the reconstruction of the blood-brain barrier and up-regulate the scavenger receptor CD36. But in chronic diseases such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), OPN can cause microglia to engulf neurons and worsen disease progression. We explored the role of OPN in promoting microglial phagocytosis in nervous system disorders.

TCM in post stroke brain remodeling: Research advances

Brain functional remodeling is fundamental to the recovery from stroke and is one of the hot topics in modern brain science research, involving various factors such as neurophysiology, neurochemistry, and neuroimaging. Traditional Chinese Medicine (TCM), with its multi-target and multi-stage effects on the body, has unique advantages in improving neurological functions and promoting brain functional remodeling. Current research mainly focuses on monotherapy with Chinese herbs, compound prescriptions, and acupuncture, among other aspects. This paper summarizes their effects and related mechanisms, aiming to provide theoretical support for the clinical application of TCM in promoting brain function recovery after stroke.

Effect of early pulmonary rehabilitation therapy on the pulmonary function of patients with stroke-associated pneumonia and analysis of its effectiveness.

This study aimed to evaluate the clinical effectiveness of early pulmonary rehabilitation (PR) treatment methods for stroke-associated pneumonia (SAP). This is a prospective, randomized controlled intervention study. Eighty SAP patients admitted to the rehabilitation department of Liuzhou People's Hospital from June 2020 to December 2021 were selected and divided into an intervention group (40 cases) and a control group (40 cases) using the random number table approach. Patients in both groups received conventional treatments. Patients in the intervention group received early PR interventions, while patients in the control group received conventional rehabilitation treatment. The clinical effectiveness and pulmonary function indexes were compared. The intervention group showed shorter durations of stay in the intensive care unit, relief from symptoms, and mechanical ventilation compared to the control group following treatment (P < 0.05). The total clinical efficacy after intervention in the treatment group was 82.50%, significantly higher than the control group's rate of 47.50% (P < 0.05). After 21 days of treatment, the forced expiratory volume in one second (FEV1)/predicted value in the intervention group was 64.92 ± 8.53, while it was 52.69 ± 7.08 in the other group. The FEV1/forced vital capacity in the intervention group was 59.73 ± 7.18, compared to 50.36 ± 6.54 in the control group. The intervention group had a clinical pulmonary infection score of 2.62 ± 1.13, while the control group had a score of 4.17 ± 2.08. The intervention group showed a significant improvement in lung function, with statistically significant differences compared to the other group (P < 0.05). Moreover, the intervention group had significantly lower levels of interleukin-4 and interleukin-10 compared to the control group, with statistical significance (P < 0.05). The average National Institute of Health Stroke Scale score of the intervention group was significantly lower than that of the control group in the second and third weeks after treatment (P < 0.05). Early comprehensive pulmonary rehabilitation can significantly enhance the pulmonary function and respiratory status of SAP patients and facilitate the early recovery of brain function. This approach archives significantly better outcomes compared to conventional PR; therefore, it is worth clinical implementation.

Mxene-bpV plays a neuroprotective role in cerebral ischemia-reperfusion injury by activating the Akt and promoting the M2 microglial polarization signaling pathways

Studies have shown that the inhibition of phosphatase and tensin homolog deleted on chromosome 10 (PTEN)was neuroprotective against ischemia/reperfusion(I/R) injury. Bisperoxovanadium (bpV), a derivative of vanadate, is a well-established inhibitor of PTEN. However, its function islimited due to its general inadequacy in penetrating cell membranes. Mxene(Ti3C2Tx) is a novel two-dimensional lamellar nanomaterial with an excellent ability to penetrate the cell membrane. Yet, the effects of this nanomaterial on nervous system diseases have yet to be scrutinized. Here, Mxene(Ti3C2Tx) was used for the first time to carry bpV(HOpic), creating a new nanocomposite Mxene-bpV that was probed in a cerebral I/R injury model. The findings showed that this synthetic Mxene-bpV was adequately stable and can cross the cell membraneeasily. We observed that Mxene-bpV treatment significantly increased the survival rate of oxygen glucose deprivation/reperfusion(OGD/R)--insulted neurons, reduced infarct sizes and promoted the recovery of brain function after mice cerebral I/R injury. Crucially, Mxene-bpV treatment was more therapeutically efficient than bpV(HOpic) treatment alone over the same period. Mechanistically, Mxene-bpV inhibited the enzyme activity of PTEN in vitro and in vivo. It also promoted the expression of phospho-Akt (Ser473) by repressing PTEN and then activated the Akt pathway to boost cell survival. Additionally, in PTEN transgenic mice, Mxene-bpV suppressed I/R-induced inflammatory response by promoting M2 microglial polarization through PTEN inhibition. Collectively, the nanosynthetic Mxene-bpV inhibited PTEN’ enzymatic activity by activating Akt pathway and promoting M2 microglial polarization, and finally exerted neuroprotection against cerebral I/R injury.Graphical

Genistein-3′-sodium sulfonate promotes brain functional rehabilitation in ischemic stroke rats by regulating astrocytes polarization through NF-κB signaling pathway

The activation and polarization of astrocytes are involved in neuroinflammation and brain functional rehabilitation after ischemic stroke. Our previous studies display the neuroprotective effect of genistein-3′-sodium sulfonate (GSS) in the acute phase of cerebral ischemia-reperfusion injury (CI/RI). This study aimed to investigate the brain function improvement of GSS during the recovery period after CI/RI in rats and to explore the potential mechanism from the perspective of astrocyte activation and polarization. The transient middle cerebral artery occlusion (tMCAO) rats were treated with GSS (1 mg/kg) continuously for 28 days. The behavior tests were measured to assess neurological function. The mRNA and protein expression in affected cerebral cortex were detected on day 29 after tMCAO. Our results demonstrated that GSS treatment significantly improved the spatial and temporal gait parameters in the Catwalk gait test, prolonged the time on the stick and increased the rotation speed in the rotarod test, and decreased the time to find the hidden platform and increased the time in the target quadrant in the Morris water maze test. In addition, GFAP, GBP2, C3, IL-1β protein expressions and Nos2A mRNA level were decreased, while Nrf2, BDNF, IL-10 protein expressions and Sphk1 and Nef2l2 mRNA levels increased after GSS treatment. Interestingly, GSS presented a strong binding affinity to TLR4 and suppressed the activation of NF-κB signaling. In conclusion, GSS can promote brain function recovery by inhibiting astrocyte activation and polarization to A1 phenotype, and enhancing astrocyte polarization to A2 phenotype via inactivating TLR4/NF-κB signaling, which provide a candidate compound for clinical rehabilitation therapy in the recovery period after ischemic stroke.

RNA sequencing reveals the potential mechanism of exercise preconditioning for cerebral ischemia reperfusion injury in rats.

Cerebral ischemia reperfusion injury (CIRI) often leads to deleterious complications after stroke patients receive reperfusion therapy. Exercise preconditioning (EP) has been reported to facilitate brain function recovery. We aim to explore the specific mechanism of EP in CIRI. Sprague-Dawley rats were randomized into Sham, middle cerebral artery occlusion (MCAO), and EP groups (n=11). The rats in the EP group received adaptive training for 3 days (10m/min, 20min/day, with a 0° incline) and formal training for 3 weeks (6 days/week, 25m/min, 30min/day, with a 0° incline). Then, rats underwent MCAO surgery to establish CIRI models. After 48h, neurological deficits and cerebral infarction of the rats were measured. Neuronal death and apoptosis in the cerebral cortices were detected. Furthermore, RNA sequencing was conducted to investigate the specific mechanism of EP on CIRI, and qPCR and Western blotting were further applied to confirm RNA sequencing results. EP improved neurological deficit scores and reduced cerebral infarction in MCAO rats. Additionally, pre-ischemic exercise also alleviated neuronal death and apoptosis of the cerebral cortices in MCAO rats. Importantly, 17 differentially expressed genes (DEGs) were identified through RNA sequencing, and these DEGs were mainly enriched in the HIF-1 pathway, cellular senescence, proteoglycans in cancer, and so on. qPCR and Western blotting further confirmed that EP could suppress TIMP1, SOCS3, ANGPTL4, CDO1, and SERPINE1 expressions in MCAO rats. EP can improve CIRI in vivo, the mechanism may relate to TIMP1 expression and HIF-1 pathway, which provided novel targets for CIRI treatment.

Leukocyte filtration and leukocyte modulation therapy during extracorporeal cardiopulmonary resuscitation in a porcine model of prolonged cardiac arrest

Extracorporeal cardiopulmonary resuscitation (ECPR) is emerging as a feasible and effective rescue strategy for prolonged cardiac arrest (CA). However, prolonged total body ischemia and reperfusion can cause microvascular occlusion that prevents organ reperfusion and recovery of function. One hypothesized mechanism of microvascular “no-reflow” is leukocyte adhesion and formation of neutrophil extracellular traps. In this study we tested the hypothesis that a leukocyte filter (LF) or leukocyte modulation device (L-MOD) could reduce NETosis and improve recovery of heart and brain function in a swine model of prolonged cardiac arrest treated with ECPR. Thirty-six swine (45.5 ± 2.5 kg, evenly distributed sex) underwent 8 min of untreated ventricular fibrillation CA followed by 30 min of mechanical CPR with subsequent 8 h of ECPR. Two females were later excluded from analysis due to CPR complications. Swine were randomized to standard care (Control group), LF, or L-MOD at the onset of CPR. NET formation was quantified by serum dsDNA and citrullinated histone as well as immunofluorescence staining of the heart and brain for citrullinated histone in the microvasculature. Primary outcomes included recovery of cardiac function based on cardiac resuscitability score (CRS) and recovery of neurologic function based on the somatosensory evoked potential (SSEP) N20 cortical response. In this model of prolonged CA treated with ECPR we observed significant increases in serum biomarkers of NETosis and immunohistochemical evidence of microvascular NET formation in the heart and brain that were not reduced by LF or L-MOD therapy. Correspondingly, there were no significant differences in CRS and SSEP recovery between Control, LF, and L-MOD groups 8 h after ECPR onset (CRS = 3.1 ± 2.7, 3.7 ± 2.6, and 2.6 ± 2.6 respectively; p = 0.606; and SSEP = 27.9 ± 13.0%, 36.7 ± 10.5%, and 31.2 ± 9.8% respectively, p = 0.194). In this model of prolonged CA treated with ECPR, the use of LF or L-MOD therapy during ECPR did not reduce microvascular NETosis or improve recovery of myocardial or brain function. The causal relationship between microvascular NETosis, no-reflow, and recovery of organ function after prolonged cardiac arrest treated with ECPR requires further investigation.

Neuritogenic glycosaminoglycan hydrogels promote functional recovery after severe traumatic brain injury

Objective. Severe traumatic brain injury (sTBI) induced neuronal loss and brain atrophy contribute significantly to long-term disabilities. Brain extracellular matrix (ECM) associated chondroitin sulfate (CS) glycosaminoglycans promote neural stem cell (NSC) maintenance, and CS hydrogel implants have demonstrated the ability to enhance neuroprotection, in preclinical sTBI studies. However, the ability of neuritogenic chimeric peptide (CP) functionalized CS hydrogels in promoting functional recovery, after controlled cortical impact (CCI) and suction ablation (SA) induced sTBI, has not been previously demonstrated. We hypothesized that neuritogenic (CS)CP hydrogels will promote neuritogenesis of human NSCs, and accelerate brain tissue repair and functional recovery in sTBI rats. Approach. We synthesized chondroitin 4-O sulfate (CS-A)CP, and 4,6-O-sulfate (CS-E)CP hydrogels, using strain promoted azide-alkyne cycloaddition (SPAAC), to promote cell adhesion and neuritogenesis of human NSCs, in vitro; and assessed the ability of (CS-A)CP hydrogels in promoting tissue and functional repair, in a novel CCI-SA sTBI model, in vivo. Main results. Results indicated that (CS-E)CP hydrogels significantly enhanced human NSC aggregation and migration via focal adhesion kinase complexes, when compared to NSCs in (CS-A)CP hydrogels, in vitro. In contrast, NSCs encapsulated in (CS-A)CP hydrogels differentiated into neurons bearing longer neurites and showed greater spontaneous activity, when compared to those in (CS-E)CP hydrogels. The intracavitary implantation of (CS-A)CP hydrogels, acutely after CCI-SA-sTBI, prevented neuronal and axonal loss, as determined by immunohistochemical analyses. (CS-A)CP hydrogel implanted animals also demonstrated the significantly accelerated recovery of ‘reach-to-grasp’ function when compared to sTBI controls, over a period of 5-weeks. Significance. These findings demonstrate the neuritogenic and neuroprotective attributes of (CS)CP ‘click’ hydrogels, and open new avenues for the development of multifunctional glycomaterials that are functionalized with biorthogonal handles for sTBI repair.

Neuraminidase inhibition promotes the collective migration of neurons and recovery of brain function

In the injured brain, new neurons produced from endogenous neural stem cells form chains and migrate to injured areas and contribute to the regeneration of lost neurons. However, this endogenous regenerative capacity of the brain has not yet been leveraged for the treatment of brain injury. Here, we show that in healthy brain chains of migrating new neurons maintain unexpectedly large non-adherent areas between neighboring cells, allowing for efficient migration. In instances of brain injury, neuraminidase reduces polysialic acid levels, which negatively regulates adhesion, leading to increased cell–cell adhesion and reduced migration efficiency. The administration of zanamivir, a neuraminidase inhibitor used for influenza treatment, promotes neuronal migration toward damaged regions, fosters neuronal regeneration, and facilitates functional recovery. Together, these findings shed light on a new mechanism governing efficient neuronal migration in the adult brain under physiological conditions, pinpoint the disruption of this mechanism during brain injury, and propose a promising therapeutic avenue for brain injury through drug repositioning.

Evaluation of Brain Function Recovery After Traumatic Brain Injury Treatment in a Porcine Model by Cross-Group Temporal-Spatial Correlation Analysis.

Traumatic brain injury (TBI), a significant global health issue, is affecting ∼69 million annually. To better understand TBI's impact on brain function and assess the efficacy of treatments, this study uses a novel temporal-spatial cross-group approach with a porcine model, integrating resting-state functional magnetic resonance imaging (rs-fMRI) for temporal and arterial spin labeling for spatial information. Our research used 18 four-week-old pigs divided into three groups: TBI treated with saline (SLN, n = 6), TBI treated with fecal microbial transplant (FMT, n = 6), and a sham group (sham, n = 6) with only craniectomy surgery as the baseline. By applying machine learning techniques-specifically, independent component analysis and sparse dictionary learning-across seven identified resting-state networks, we assessed the temporal and spatial correlations indicative of treatment efficacy. Both temporal and spatial analyses revealed a consistent increase of correlation between the FMT and sham groups in the executive control and salience networks. Our results are further evidenced by a simulation study designed to mimic the progression of TBI severity through the introduction of variable Gaussian noise to an independent rs-fMRI dataset. The results demonstrate a decreasing temporal correlation between the sham and TBI groups with increasing injury severity, consistent with the experimental results. This study underscores the effectiveness of the methodology in evaluating post-TBI treatments such as the FMT. By presenting comprehensive experimental and simulated data, our research contributes significantly to the field and opens new paths for future investigations into TBI treatment evaluations.

Resting-state functional connectivity in children cooled for neonatal encephalopathy.

Therapeutic hypothermia improves outcomes following neonatal hypoxic-ischaemic encephalopathy, reducing cases of death and severe disability such as cerebral palsy compared with normothermia management. However, when cooled children reach early school-age, they have cognitive and motor impairments which are associated with underlying alterations to brain structure and white matter connectivity. It is unknown whether these differences in structural connectivity are associated with differences in functional connectivity between cooled children and healthy controls. Resting-state functional MRI has been used to characterize static and dynamic functional connectivity in children, both with typical development and those with neurodevelopmental disorders. Previous studies of resting-state brain networks in children with hypoxic-ischaemic encephalopathy have focussed on the neonatal period. In this study, we used resting-state fMRI to investigate static and dynamic functional connectivity in children aged 6-8 years who were cooled for neonatal hypoxic-ischaemic without cerebral palsy [n = 22, median age (interquartile range) 7.08 (6.85-7.52) years] and healthy controls matched for age, sex and socioeconomic status [n = 20, median age (interquartile range) 6.75 (6.48-7.25) years]. Using group independent component analysis, we identified 31 intrinsic functional connectivity networks consistent with those previously reported in children and adults. We found no case-control differences in the spatial maps of these intrinsic connectivity networks. We constructed subject-specific static functional connectivity networks by measuring pairwise Pearson correlations between component time courses and found no case-control differences in functional connectivity after false discovery rate correction. To study the time-varying organization of resting-state networks, we used sliding window correlations and deep clustering to investigate dynamic functional connectivity characteristics. We found k = 4 repetitively occurring functional connectivity states, which exhibited no case-control differences in dwell time, fractional occupancy or state functional connectivity matrices. In this small cohort, the spatiotemporal characteristics of resting-state brain networks in cooled children without severe disability were too subtle to be differentiated from healthy controls at early school-age, despite underlying differences in brain structure and white matter connectivity, possibly reflecting a level of recovery of healthy resting-state brain function. To our knowledge, this is the first study to investigate resting-state functional connectivity in children with hypoxic-ischaemic encephalopathy beyond the neonatal period and the first to investigate dynamic functional connectivity in any children with hypoxic-ischaemic encephalopathy.

Updates of the role of B-cells in ischemic stroke.

Ischemic stroke is a major disease causing death and disability in the elderly and is one of the major diseases that seriously threaten human health and cause a great economic burden. In the early stage of ischemic stroke, neuronal structure is destroyed, resulting in death or damage, and the release of a variety of damage-associated pattern molecules induces an increase in neuroglial activation, peripheral immune response, and secretion of inflammatory mediators, which further exacerbates the damage to the blood-brain barrier, exacerbates cerebral edema, and microcirculatory impairment, triggering secondary brain injuries. After the acute phase of stroke, various immune cells initiate a protective effect, which is released step by step and contributes to the repair of neuronal cells through phenotypic changes. In addition, ischemic stroke induces Central Nervous System (CNS) immunosuppression, and the interaction between the two influences the outcome of stroke. Therefore, modulating the immune response of the CNS to reduce the inflammatory response and immune damage during stroke is important for the protection of brain function and long-term recovery after stroke, and modulating the immune function of the CNS is expected to be a novel therapeutic strategy. However, there are fewer studies on B-cells in brain function protection, which may play a dual role in the stroke process, and the understanding of this cell is still incomplete. We review the existing studies on the mechanisms of the role of B-cells, inflammatory response, and immune response in the development of ischemic stroke and provide a reference for the development of adjuvant therapeutic drugs for ischemic stroke targeting inflammatory injury.

Biomaterials and tissue engineering in traumatic brain injury: novel perspectives on promoting neural regeneration.

Traumatic brain injury is a serious medical condition that can be attributed to falls, motor vehicle accidents, sports injuries and acts of violence, causing a series of neural injuries and neuropsychiatric symptoms. However, limited accessibility to the injury sites, complicated histological and anatomical structure, intricate cellular and extracellular milieu, lack of regenerative capacity in the native cells, vast variety of damage routes, and the insufficient time available for treatment have restricted the widespread application of several therapeutic methods in cases of central nervous system injury. Tissue engineering and regenerative medicine have emerged as innovative approaches in the field of nerve regeneration. By combining biomaterials, stem cells, and growth factors, these approaches have provided a platform for developing effective treatments for neural injuries, which can offer the potential to restore neural function, improve patient outcomes, and reduce the need for drugs and invasive surgical procedures. Biomaterials have shown advantages in promoting neural development, inhibiting glial scar formation, and providing a suitable biomimetic neural microenvironment, which makes their application promising in the field of neural regeneration. For instance, bioactive scaffolds loaded with stem cells can provide a biocompatible and biodegradable milieu. Furthermore, stem cells-derived exosomes combine the advantages of stem cells, avoid the risk of immune rejection, cooperate with biomaterials to enhance their biological functions, and exert stable functions, thereby inducing angiogenesis and neural regeneration in patients with traumatic brain injury and promoting the recovery of brain function. Unfortunately, biomaterials have shown positive effects in the laboratory, but when similar materials are used in clinical studies of human central nervous system regeneration, their efficacy is unsatisfactory. Here, we review the characteristics and properties of various bioactive materials, followed by the introduction of applications based on biochemistry and cell molecules, and discuss the emerging role of biomaterials in promoting neural regeneration. Further, we summarize the adaptive biomaterials infused with exosomes produced from stem cells and stem cells themselves for the treatment of traumatic brain injury. Finally, we present the main limitations of biomaterials for the treatment of traumatic brain injury and offer insights into their future potential.

Use of magnetic source imaging to assess recovery after severe traumatic brain injury-an MEG pilot study.

Severe TBI (sTBI) is a devastating neurological injury that comprises a significant global trauma burden. Early comprehensive neurocritical care and rehabilitation improve outcomes for such patients, although better diagnostic and prognostic tools are necessary to guide personalized treatment plans. In this study, we explored the feasibility of conducting resting state magnetoencephalography (MEG) in a case series of sTBI patients acutely after injury (~7 days), and then about 1.5 and 8 months after injury. Synthetic aperture magnetometry (SAM) was utilized to localize source power in the canonical frequency bands of delta, theta, alpha, beta, and gamma, as well as DC-80 Hz. At the first scan, SAM source maps revealed zones of hypofunction, islands of preserved activity, and hemispheric asymmetry across bandwidths, with markedly reduced power on the side of injury for each patient. GCS scores improved at scan 2 and by scan 3 the patients were ambulatory. The SAM maps for scans 2 and 3 varied, with most patients showing increasing power over time, especially in gamma, but a continued reduction in power in damaged areas and hemispheric asymmetry and/or relative diminishment in power at the site of injury. At the group level for scan 1, there was a large excess of neural generators operating within the delta band relative to control participants, while the number of neural generators for beta and gamma were significantly reduced. At scan 2 there was increased beta power relative to controls. At scan 3 there was increased group-wise delta power in comparison to controls. In summary, this pilot study shows that MEG can be safely used to monitor and track the recovery of brain function in patients with severe TBI as well as to identify patient-specific regions of decreased or altered brain function. Such MEG maps of brain function may be used in the future to tailor patient-specific rehabilitation plans to target regions of altered spectral power with neurostimulation and other treatments.

Targeting Neurogenesis in Seeking Novel Treatments for Ischemic Stroke.

The interruption of cerebral blood flow leads to ischemic cell death and results in ischemic stroke. Although ischemic stroke is one of the most important causes of long-term disability and mortality, limited treatments are available for functional recovery. Therefore, extensive research has been conducted to identify novel treatments. Neurogenesis is regarded as a fundamental mechanism of neural plasticity. Therefore, therapeutic strategies targeting neurogenesis are thought to be promising. Basic research has found that therapeutic intervention including cell therapy, rehabilitation, and pharmacotherapy increased neurogenesis and was accompanied by functional recovery after ischemic stroke. In this review, we consolidated the current knowledge of the relationship between neurogenesis and treatment for ischemic stroke. It revealed that many treatments for ischemic stroke, including clinical and preclinical ones, have enhanced brain repair and functional recovery post-stroke along with neurogenesis. However, the intricate mechanisms of neurogenesis and its impact on stroke recovery remain areas of extensive research, with numerous factors and pathways involved. Understanding neurogenesis will lead to more effective stroke treatments, benefiting not only stroke patients but also those with other neurological disorders. Further research is essential to bridge the gap between preclinical discoveries and clinical implementation.

Low-temperature 3D-printed collagen/chitosan scaffolds loaded with exosomes derived from neural stem cells pretreated with insulin growth factor-1 enhance neural regeneration after traumatic brain injury.

There are various clinical treatments for traumatic brain injury, including surgery, drug therapy, and rehabilitation therapy; however, the therapeutic effects are limited. Scaffolds combined with exosomes represent a promising but challenging method for improving the repair of traumatic brain injury. In this study, we determined the ability of a novel 3D-printed collagen/chitosan scaffold loaded with exosomes derived from neural stem cells pretreated with insulin-like growth factor-1 (3D-CC-INExos) to improve traumatic brain injury repair and functional recovery after traumatic brain injury in rats. Composite scaffolds comprising collagen, chitosan, and exosomes derived from neural stem cells pretreated with insulin-like growth factor-1 (INExos) continuously released exosomes for 2 weeks. Transplantation of 3D-CC-INExos scaffolds significantly improved motor and cognitive functions in a rat traumatic brain injury model, as assessed by the Morris water maze test and modified neurological severity scores. In addition, immunofluorescence staining and transmission electron microscopy showed that 3D-CC-INExos implantation significantly improved the recovery of damaged nerve tissue in the injured area. In conclusion, this study suggests that transplanted 3D-CC-INExos scaffolds might provide a potential strategy for the treatment of traumatic brain injury and lay a solid foundation for clinical translation.

Untargeted metabonomic analysis of a cerebral stroke model in rats: a study based on UPLC-MS/MS.

Brain tissue damage caused by ischemic stroke can trigger changes in the body's metabolic response, and understanding the changes in the metabolic response of the gut after stroke can contribute to research on poststroke brain function recovery. Despite the increase in international research on poststroke metabolic mechanisms and the availability of powerful research tools in recent years, there is still an urgent need for poststroke metabolic studies. Metabolomic examination of feces from a cerebral ischemia-reperfusion rat model can provide new insights into poststroke metabolism and identify key metabolic pathways, which will help reveal diagnostic and therapeutic targets as well as inspire pathophysiological studies after stroke. We randomly divided 16 healthy adult pathogen-free male Sprague-Dawley (SD) rats into the normal group and the study group, which received middle cerebral artery occlusion/reperfusion (MCAO/R). Ultra-performance liquid chromatography-tandem mass spectrometry (UPLCMS/MS) was used to determine the identities and concentrations of metabolites across all groups, and filtered high-quality data were analyzed for differential screening and differential metabolite functional analysis. After 1 and 14 days of modeling, compared to the normal group, rats in the study group showed significant neurological deficits (p < 0.001) and significantly increased infarct volume (day 1: p < 0.001; day 14: p = 0.001). Mass spectra identified 1,044 and 635 differential metabolites in rat feces in positive and negative ion modes, respectively, which differed significantly between the normal and study groups. The metabolites with increased levels identified in the study group were involved in tryptophan metabolism (p = 0.036678, p < 0.05), arachidonic acid metabolism (p = 0.15695), cysteine and methionine metabolism (p = 0.24705), and pyrimidine metabolism (p = 0.3413), whereas the metabolites with decreased levels were involved in arginine and proline metabolism (p = 0.15695) and starch and sucrose metabolism (p = 0.52256). We determined that UPLC-MS/MS could be employed for untargeted metabolomics research. Moreover, tryptophan metabolic pathways may have been disordered in the study group. Alterations in the tryptophan metabolome may provide additional theoretical and data support for elucidating stroke pathogenesis and selecting pathways for intervention.

Probucol treatment after traumatic brain injury activates BDNF/TrkB pathway, promotes neuroregeneration and ameliorates functional deficits in mice.

Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide, yet pharmacotherapies for TBI are currently lacking. Neuroregeneration is important in brain repair and functional recovery. In this study, probucol, a cholesterol-lowering drug with established safety profiles, was examined for its therapeutic effects and neuroregenerative actions in TBI. Male mice were subjected to the controlled cortical impact model of TBI, followed by daily administration of probucol. Neurological and cognitive functions were evaluated. Histological analyses of the neocortex and hippocampus were performed to detect the lesion, dendritic degeneration (microtubule-associated protein 2), synaptic density (synaptophysin), neurogenesis (doublecortin), brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) activation. Involvement of BDNF/TrkB pathway in probucol-mediated effects was examined in primary cultures of cortical neurons. Probucol reduced brain lesion volume, enhanced the recovery of body symmetry, improved motor function and attenuated memory dysfunction after TBI. Meanwhile, probucol promoted post-injury dendritic growth and synaptogenesis and increased hippocampal proliferating neuronal progenitor cells, along with the formation as well as the survival of newborn neurons. Moreover, probucol enhances BDNF expression and TrkB activation. In vitro, probucol promoted neurite outgrowth, which was inhibited by a selective TrkB antagonist ANA-12. Probucol enhanced functional restoration and ameliorated cognitive impairment after TBI by promoting post-injury neuronal remodelling and neurogenesis. Increased activation of BDNF/TrkB pathway by probucol, at least in part, contributed to the neuroregenerative effects of probucol. Together, it may be promising to repurpose probucol for TBI.