Transplanted Bone Marrow Mesenchymal Stem Cells Improve Memory in Rat Models of Alzheimer's Disease

The present study aims to evaluate the effect of bone marrow mesenchymal stem cells (MSCs) grafts on cognition deficit in chemically and age-induced Alzheimer's models of rats. In the first experiments aged animals (30 months) were tested in Morris water maze (MWM) and divided into two groups: impaired memory and unimpaired memory. Impaired groups were divided into two groups and cannulated bilaterally at the CA1 of the hippocampus for delivery of mesenchymal stem cells (500 × 103/μL) and PBS (phosphate buffer saline). In the second experiment, Ibotenic acid (Ibo) was injected bilaterally into the nucleus basalis magnocellularis (NBM) of young rats (3 months) and animals were tested in MWM. Then, animals with memory impairment received the following treatments: MSCs (500 × 103/μL) and PBS. Two months after the treatments, cognitive recovery was assessed by MWM in relearning paradigm in both experiments. Results showed that MSCs treatment significantly increased learning ability and memory in both age- and Ibo-induced memory impairment. Adult bone marrow mesenchymal stem cells show promise in treating cognitive decline associated with aging and NBM lesions

Myelin damage and repair in pathologic CNS: challenges and prospects

Injury to the central nervous system (CNS) results in oligodendrocyte cell death and progressive demyelination. Demyelinated axons undergo considerable physiological changes and molecular reorganizations that collectively result in axonal dysfunction, degeneration and loss of sensory and motor functions. Endogenous adult oligodendrocyte precursor cells (OPCs) and neural stem/progenitor cells (NPCs) contribute to the replacement of oligodendrocytes, however, the extent and quality of endogenous remyelination is suboptimal. Emerging evidence indicates that optimal remyelination is restricted by multiple factors including (i) low levels of factors that promote oligodendrogenesis; (ii) cell death among newly generated oligodendrocytes, (iii) inhibitory factors in the post-injury milieu that impede remyelination, and (iv) deficient expression of key growth factors essential for proper re-construction of a highly organized myelin sheath. Considering these challenges, over the past several years, a number of cell-based strategies have been developed to optimize remyelination therapeutically. Outcomes of these basic and preclinical discoveries are promising and signify the importance of remyelination as a mechanism for improving functions in CNS injuries. In this review, we provide an overview on: 1) the precise organization of myelinated axons and the reciprocal axo-myelin interactions that warrant properly balanced physiological activities within the CNS; 2) underlying cause of demyelination and the structural and functional consequences of demyelination in axons following injury and disease; 3) the endogenous mechanisms of oligodendrocyte replacement; 4) the modulatory role of reactive astrocytes and inflammatory cells in remyelination; and 5) the current status of cell-based therapies for promoting remyelination. Careful elucidation of the cellular and molecular mechanisms of demyelination in the pathologic CNS is a key to better understanding the impact of remyelinati

Kidney disease improving global outcome for predicting acute kidney injury in traumatic brain injury patients

AbstractAimTo determine the incidence of acute kidney injury (AKI) based on Kidney Disease Improving Global Outcome (KDIGO) criteria in patients with severe traumatic brain injury and to study AKI in relation to risk factors and outcomes.MethodThis trial was a descriptive analytic study on 83 patients with severe traumatic brain injury admitted to Poursina Hospital (Rasht, Iran). The incidence of AKI was determined based on KDIGO criteria over a 12-month period. The correlation of mortality rates, multi-organ failure (MOF), and neurologic outcome to AKI were studied.ResultsOf 83 eligible patients who entered the study, 25.3% (N=21) developed AKI based on KDIGO criteria. Glasgow Outcome Scale on admission was the only risk factor significantly associated with the incidence of AKI (p=0.001). Mortality rates (62% vs. 22.6%, p=0.002) and the occurrence of MOF were significantly higher in patients who developed AKI (23.8% vs. 0% MOF based on Sequential Organ Failure Assessment, p<0.0001; 19% vs. 0% MOF based on Multiple Organ Dysfunction score, p<0.0001). Poor neurologic outcome was observed in 95% and 92% of patients with and without AKI, respectively (p=0.674).ConclusionThe incidence of AKI among patients with severe traumatic brain injury is striking. The association of Glasgow Outcome Scale with AKI helps to identify patients at a higher risk of developing AKI. Significant rates of mortality and MOF among patients with severe traumatic brain injury and AKI, necessitates consideration of renoprotective measures from the early days of hospital admission

Continuous Time-Domain Cerebrovascular Reactivity Metrics and Discriminate Capacity for the Upper and Lower Limits of Autoregulation: A Scoping Review of the Animal Literature.

Over a wide range of systemic arterial pressures, cerebral blood flow (CBF) is regulated fairly constantly by the cerebral vessels in a process termed cerebral autoregulation (CA), which is depicted by the Lassen autoregulatory curve. After traumatic brain injury (TBI), CA can get impaired and these impairments manifest in changes of the Lassen autoregulatory curve. Continuous surrogate metrics of pressure-based CA, termed cerebrovascular reactivity (CVR) metrics, evaluate the relationship between slow vasogenic fluctuations in a driving pressure for cerebral blood flow, and the most commonly studied and utilized measures are based in the time domain and have been increasingly applied in bedside TBI care and have sparked the investigation of individualized cerebral perfusion pressure targets. However, not all CVR metrics have been validated as true measures of autoregulation in the pre-clinical setting. We reviewed all available pre-clinical animal literature that assessed the association between continuous time-domain metrics of CVR and some aspect of the Lassen autoregulatory curve. All 15 articles found associated the evaluated continuous metrics to the lower limit of autoregulation curve whereas none looked at the upper limit. Most of the evaluated metrics showed the ability to discriminate the lower limit of autoregulation with various methods of perturbation. Further work is required to evaluate the utility of such surrogate measures against the upper limit of autoregulation, while also providing validation to the existing literature supporting specific indices and their ability to discriminate the lower limit

Impact of Age and Biological Sex on Cerebrovascular Reactivity in Adult Moderate/Severe Traumatic Brain Injury: An Exploratory Analysis

Age and biological sex are two potential important modifiers of cerebrovascular reactivity post-traumatic brain injury (TBI) requiring close evaluation for potential subgroup responses. The goal of this study was to provide a preliminary exploratory analysis of the impact of age and biological sex on measures of cerebrovascular function in moderate/severe TBI. Forty-nine patients from the prospectively maintained TBI database at the University of Manitoba with archived high-frequency digital cerebral physiology were evaluated. Cerebrovascular reactivity indices were derived as follows: PRx (correlation between intracranial pressure [ICP] and mean arterial pressure [MAP]), PAx (correlation between pulse amplitude of ICP [AMP] and MAP), and RAC (correlation between AMP and cerebral perfusion pressure [CPP]). Time above clinically significant thresholds for each index was calculated over different periods of the acute intensive care unit stay. The association between PRx, PAx, and RAC measures with age was assessed using linear regression, and an age trichotomization scheme (60) using Kruskal-Wallis testing. Similarly, association with biological sex was tested using Mann-Whitney U testing. Biological sex did not demonstrate an impact on any measures of cerebrovascular reactivity. Linear regression between age and PAx and RAC demonstrated a statistically significant positive linear relationship. Median PAx and RAC measures between trichotomized age categories demonstrated statistically significant increases with advancing age. The PRx failed to demonstrate any statistically significant relationship with age in this cohort, suggesting that in elderly patients with controlled ICP, PAx and RAC may be better metrics for detecting impaired cerebrovascular reactivity. Biological sex appears to not be associated with differences in cerebrovascular reactivity in this cohort. The PRx performed the worst in detecting impaired cerebrovascular reactivity in those with advanced age, where PAx and RAC appear to have excelled. Future work is required to validate these findings and explore the utility of different cerebrovascular reactivity indices

Near Infrared Spectroscopy for High-Temporal Resolution Cerebral Physiome Characterization in TBI: A Narrative Review of Techniques, Applications, and Future Directions.

Multimodal monitoring has been gaining traction in the critical care of patients following traumatic brain injury (TBI). Through providing a deeper understanding of the individual patient's comprehensive physiologic state, or "physiome," following injury, these methods hold the promise of improving personalized care and advancing precision medicine. One of the modalities being explored in TBI care is near-infrared spectroscopy (NIRS), given it's non-invasive nature and ability to interrogate microvascular and tissue oxygen metabolism. In this narrative review, we begin by discussing the principles of NIRS technology, including spatially, frequency, and time-resolved variants. Subsequently, the applications of NIRS in various phases of clinical care following TBI are explored. These applications include the pre-hospital, intraoperative, neurocritical care, and outpatient/rehabilitation setting. The utility of NIRS to predict functional outcomes and evaluate dysfunctional cerebrovascular reactivity is also discussed. Finally, future applications and potential advancements in NIRS-based physiologic monitoring of TBI patients are presented, with a description of the potential integration with other omics biomarkers

Intracranial Pressure-Derived Cerebrovascular Reactivity Indices, Chronological Age, and Biological Sex in Traumatic Brain Injury: A Scoping Review.

To date, there has been limited literature exploring the association between age and sex with cerebrovascular reactivity (CVR) in moderate/severe traumatic brain injury (TBI). Given the known link between age, sex, and cerebrovascular function, knowledge of the impacts on continuously assessed CVR is critical for the development of future therapeutics. We conducted a scoping review of the literature for studies that had a direct statistical interrogation of the relationship between age, sex, and continuous intracranial pressure (ICP)-based indices of CVR in moderate/severe TBI. The ICP-based indices researched included: pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC. MEDLINE, BIOSIS, EMBASE, SCOPUS, Global Health, and the Cochrane library were searched from inception to June 2021 for relevant articles. A total of 10 original studies fulfilled our inclusion criteria. Nine of the articles documented a correlation between advanced age and worse CVR, with eight using PRx (2192 total patients), three using PAx (978 total patients), and one using RAC (358 total patients), p < 0.05; R ranging from 0.17 to 0.495 for all indices across all studies. Three articles (1256 total patients) displayed a correlation between biological sex and PRx, with females trending towards higher PRx values (p < 0.05) in the limited available literature. However, no literature exists comparing PAx or RAC with biological sex. Findings showed that aging was associated with impaired CVR. We observed a trend between female sex and worse PRx values, but the literature was limited and statistical significance was borderline. The identified studies were few in number, carried significant population heterogeneity, and utilized grand averaging of large epochs of physiology during statistical comparisons with age and biological sex. Because of the heterogeneous nature of TBI populations and limited focus on the effects of age and sex on outcomes in TBI, it is challenging to highlight the differences between the indices and patient age groups and sex. The largest study showing an association between PRx and age was done by Zeiler and colleagues, where 165 patients were studied noting that patients with a mean PRx value above zero had a mean age above 51.4 years versus a mean age of 41.4 years for those with a mean PRx value below zero (p = 0.0007). The largest study showing an association between PRx and sex was done by Czosnyka and colleagues, where 469 patients were studied noting that for patients <50 years of age, PRx was worse in females (0.11 ± 0.047) compared to males (0.044 ± 0.031), p < 0.05. The findings from these 10 studies provide preliminary data, but are insufficient to definitively characterize the impact of age and sex on CVR in moderate/severe TBI. Future work in the field should focus on the impact of age and sex on multi-modal cerebral physiological monitoring

Dynamic Temporal Relationship Between Autonomic Function and Cerebrovascular Reactivity in Moderate/Severe Traumatic Brain Injury.

There has been little change in morbidity and mortality in traumatic brain injury (TBI) in the last 25 years. However, literature has emerged linking impaired cerebrovascular reactivity (a surrogate of cerebral autoregulation) with poor outcomes post-injury. Thus, cerebrovascular reactivity (derived through the pressure reactivity index; PRx) is emerging as an important continuous measure. Furthermore, recent literature indicates that autonomic dysfunction may drive impaired cerebrovascular reactivity in moderate/severe TBI. Thus, to improve our understanding of this association, we assessed the physiological relationship between PRx and the autonomic variables of heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS) using time-series statistical methodologies. These methodologies include vector autoregressive integrative moving average (VARIMA) impulse response function analysis, Granger causality, and hierarchical clustering. Granger causality testing displayed inconclusive results, where PRx and the autonomic variables had varying bidirectional relationships. Evaluating the temporal profile of the impulse response function plots demonstrated that the autonomic variables of BRS, ratio of low/high frequency of HRV and very low frequency HRV all had a strong relation to PRx, indicating that the sympathetic autonomic response may be more closely linked to cerebrovascular reactivity, then other variables. Finally, BRS was consistently associated with PRx, possibly demonstrating a deeper relationship to PRx than other autonomic measures. Taken together, cerebrovascular reactivity and autonomic response are interlinked, with a bidirectional impact between cerebrovascular reactivity and circulatory autonomics. However, this work is exploratory and preliminary, with further study required to extract and confirm any underlying relationships

Ocean remote sensing techniques and applications: a review (Part II)

As discussed in the first part of this review paper, Remote Sensing (RS) systems are great tools to study various oceanographic parameters. Part I of this study described different passive and active RS systems and six applications of RS in ocean studies, including Ocean Surface Wind (OSW), Ocean Surface Current (OSC), Ocean Wave Height (OWH), Sea Level (SL), Ocean Tide (OT), and Ship Detection (SD). In Part II, the remaining nine important applications of RS systems for ocean environments, including Iceberg, Sea Ice (SI), Sea Surface temperature (SST), Ocean Surface Salinity (OSS), Ocean Color (OC), Ocean Chlorophyll (OCh), Ocean Oil Spill (OOS), Underwater Ocean, and Fishery are comprehensively reviewed and discussed. For each application, the applicable RS systems, their advantages and disadvantages, various RS and Machine Learning (ML) techniques, and several case studies are discussed.Peer ReviewedPostprint (published version

Frequency of Minor Skin and Soft Tissue Complications in Facial and Periorbital Area after Septorhinoplasty

Introduction: High prevalence of rhinoplasty in the community and lack of structured studies about its minor skin and soft tissue complications, point out the necessity of performing precise and comprehensive studies. The aim of this study was to determine the frequency of minor cutaneous and soft tissue complications of rhinoplasty.  Materials and Methods: 110 patients (30 Male and 80 Female, Mean age: 26.3± 6.8) participated in this study. Before surgery all of them were checked for having each of intended complications, and 1 and 3 months after the surgery, they underwent serial visits for monitoring skin & soft tissue complications. The software used for data analysis was SPSS ver.16.  Results: Acne exacerbation was seen in 27% of cases in first post-surgical visit. Nasal tip paresthesia was the most frequent complication in both postsurgical visits (49.6% in first and 36.3% in second visit), followed by eyebrow loss (31.8%), complaint of increased yawning (31.8%), periorbital hyperpigmentation (21.8%) in first visit, and, hyperpigmentation (19.1%), complaint of increased yawning (10%) and surgical site scar (7.2%) in second visit respectively. The frequency of complications was highest in younger than 25 year old age group.  Conclusion: Having knowledge about these complications helps us to know which of them needs prompt medical intervention and which of them will resolve with time and just needs giving reassurance to the patient