Perivascular neurons instruct 3D vascular lattice formation via neurovascular contact.

The vasculature of the central nervous system is a 3D lattice composed of laminar vascular beds interconnected by penetrating vessels. The mechanisms controlling 3D lattice network formation remain largely unknown. Combining viral labeling, genetic marking, and single-cell profiling in the mouse retina, we discovered a perivascular neuronal subset, annotated as Fam19a4/Nts-positive retinal ganglion cells (Fam19a4/Nts-RGCs), directly contacting the vasculature with perisomatic endfeet. Developmental ablation of Fam19a4/Nts-RGCs led to disoriented growth of penetrating vessels near the ganglion cell layer (GCL), leading to a disorganized 3D vascular lattice. We identified enriched PIEZO2 expression in Fam19a4/Nts-RGCs. Piezo2 loss from all retinal neurons or Fam19a4/Nts-RGCs abolished the direct neurovascular contacts and phenocopied the Fam19a4/Nts-RGC ablation deficits. The defective vascular structure led to reduced capillary perfusion and sensitized the retina to ischemic insults. Furthermore, we uncovered a Piezo2-dependent perivascular granule cell subset for cerebellar vascular patterning, indicating neuronal Piezo2-dependent 3D vascular patterning in the brain.

Yoga as a Preventive Intervention for Cardiovascular Diseases and Associated Comorbidities: Open-Label Single Arm Study.

Aim: Common Yoga Protocol (CYP) is a standardized yoga protocol authored by experts from all over the world under the aegis of the Ministry of AYUSH, Ayurveda, Yoga and Naturopathy, Unani, Siddha, Sowa Rigpa and Homeopathy (AYUSH). The potential of CYP can be determined as a cost-effective lifestyle modification to prevent the risk of developing cardiovascular diseases (CVD). Methods: In this prospective trial, we compared the effect of CYP at baseline and after 1 month. A total of 374 yoga-naïve participants performed CYP under the supervision of experienced trainers. Physiological [body mass index (BMI), blood pressure, percent oxygen saturation], biochemical (fasting blood glucose and lipid profile), and neurocognitive parameters were measured before and after the intervention. Results: At day 30 of yoga practice, serum levels of low-density lipoprotein (LDL), total cholesterol (TC), and high-density lipoprotein (HDL) were found significantly improved as compared to the baseline levels observed at the time of enrollment. Similarly, the lipid profile was also obtained from experienced trainers and found to be significantly different from those of yoga-naïve volunteers. When the intervention was compared between the healthy yoga-naïve participants with yoga-naïve participants suffering from medical issues, it was found that cholesterol profile improved significantly in the healthy-naive group as compared to the diseased group (hypertension, diabetes, underwent surgery, and CVD). Conclusion: These results highlight the need for further research to better understand the effects of yoga on the primary prevention of CVD.

Role of Microglia and Astrocytes in Spinal Cord Injury Induced Neuropathic Pain.

Background: Spinal cord injuries incite varying degrees of symptoms in patients, ranging from weakness and incoordination to paralysis. Common amongst spinal cord injury (SCI) patients, neuropathic pain (NP) is a debilitating medical condition. Unfortunately, there remain many clinical impediments in treating NP because there is a lack of understanding regarding the mechanisms behind SCI-induced NP (SCINP). Given that more than 450,000 people in the United States alone suffer from SCI, it is unsatisfactory that current treatments yield poor results in alleviating and treating NP. Summary: In this review, we briefly discussed the models of SCINP along with the mechanisms of NP progression. Further, current treatment modalities are herein explored for SCINP involving pharmacological interventions targeting glia cells and astrocytes. Key message: The studies presented in this review provide insight for new directions regarding SCINP alleviation. Given the severity and incapacitating effects of SCINP, it is imperative to study the pathways involved and find new therapeutic targets in coordination with stem cell research, and to develop a new gold-standard in SCINP treatment.

Association of Plasma Biomarkers for Angiogenesis and Proteinopathy in Indian Amyotrophic Lateral Sclerosis Patients.

Background Amyotrophic lateral sclerosis (ALS) is a rare motor neuron disease with progressive degeneration of motor neurons. Various molecules have been explored to provide the early diagnostic/prognostic tool for ALS without getting much success in the field and miscellaneous reports studied in various population. Objective The study was aimed to see the differential expression of proteins involved in angiogenesis (angiogenin [ANG], vascular endothelial growth factor [VEGF], vascular endothelial growth factor receptor 2 [VEGFR2], etc), proteinopathy (transactive response DNA binding protein-43 [TDP-43] and optineurin [OPTN]), and neuroinflammation (monocyte chemoattractant protein-1[MCP-1]) based on the characteristics of ALS pathology. Though, suitable panel based on protein expression profile can be designed to robust the ALS identification by enhancing the prognostic and diagnostic efficacy for ALS. Methods A total of 89 ALS patients and 98 nonneurological controls were analyzed for the protein expression. Expression of angiogenic (VEGF, VEGFR2, and ANG), neuroinflammation (MCP-1), and proteinopathy (TDP-43 and OPTN) markers were estimated in plasma of the participants. Proteins were normalized with respective value of total protein before employing statistical analysis. Results Analysis has exhibited significantly reduced expression of angiogenic, proteinopathy, and neuroinflammation biomarkers in ALS patients in comparison to controls. Spearman's correlation analysis has showed the positive correlation to each protein. Conclusion Altered expression of these proteins is indicating the prominent function in ALS pathology which may be interdependent and may have a synergistic role. Hence, a panel of expression can be proposed to diagnose ALS patient which may also suggest the modulation of therapeutic strategy according to expression profile of patient.

Higher Perceived Stress and Poor Glycemic Changes in Prediabetics and Diabetics Among Indian Population.

Diabetes mellitus (DM) is a chronic metabolic disorder with significant co-morbidities and healthcare burdens. Many large studies have investigated the association between perceived stress and DM; however, none investigated this in a larger Indian population. We hypothesized stress as one of the reasons for the progression of people with prediabetes into DM. The present study was, therefore, planned to report on associations between perceived stress and blood glucose markers stratified by diabetic status. The current descriptive study was a subset analysis of the nationwide cross-sectional survey, conducted in all Indian zones under the National Multicentric Diabetes Control Program. The study examined the perceived stress levels using a perceived stress scale (PSS-10) in people with prediabetes (n=649) and DM (n=485) and then segregated them into three categories (minimum, moderate, and severe). Blood glucose markers (fasting blood glucose, postprandial blood glucose, and HbA1c) were evaluated to report their association with the perceived stress. The study revealed a significantly higher HbA1c level in people with prediabetes, particularly those with severe perceived stress (6.12 ± 0.27) compared to other categories. Those with DM had a higher fasting blood glucose level, particularly with severe perceived stress (239.28 ± 99.52). An increased HbA1c level is noted in severely stressed people with prediabetes, requiring a comprehensive analysis with a longitudinal study of the role of perceived stress in the progression of prediabetes into DM. Additionally, higher fasting blood glucose levels in patients with DM and severe perceived stress suggests the need for establishing comprehensive diabetic care inclusive of stress management.

Identifying putative cerebrospinal fluid biomarkers of amyotrophic lateral sclerosis in a north Indian population.

INTRODUCTION: Evidence-based information about cerebrospinal fluid (CSF) levels of biomarkers in patients with amyotrophic lateral sclerosis (ALS) is limited. METHODS: Vascular endothelial growth factor (VEGF) and its receptor vascular endothelial growth factor receptor 2 (VEGFR2), optineurin (OPTN), monocyte chemoattractant protein-1 (MCP-1), angiogenin (ANG), and TAR DNA-binding protein (TDP-43) were quantified by enzyme-linked immunoassay in the CSF of 54 patients with sporadic ALS and 32 controls in a case-control study design. RESULTS: CSF levels of VEGF (P = .014) and ANG (P = .009) were decreased, whereas VEGFR2 was higher (P = .002) in patients with ALS than in controls. TDP-43 positively correlated with MCP-1 (P = .003), VEGF (P < .001), and VEGFR2 (P < .001) in patients with ALS. DISCUSSION: Our findings suggest possible utility of VEGF, VEGFR2, and ANG as biomarkers for use in ALS treatment trials.

Angiogenesis-Centered Molecular Cross-Talk in Amyotrophic Lateral Sclerosis Survival: Mechanistic Insights.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that is characterized with progressive muscle atrophy. We have attempted to establish the link between angiogenesis and cellular survival in the pathogenesis of ALS by compiling evidence described in various scientific reports. The phenotypes of human ALS have earlier been captured in the mutant SOD1 mice as well as by targeted deletion of the hypoxia response element (HRE) from the promoter of the mouse gene for vascular endothelial growth factor (VEGF). Indirect evidence shows that angiogenesis can help prevent oxidative stress, and hence, enhance cell survival. VEGF and angiogenin chiefly regulate the process of angiogenesis. Transactive response DNA-binding protein 43 (TDP-43) is usually found inside the nucleus, but in large number of cases of ALS, it accumulates in the cytoplasm (TDP-43 proteinopathy). Interestingly, TDP-43 proteinopathy is found to be aggravated in the presence of the OPTN mutation, which is the genetic factor that is responsible for such accumulation. Interaction of TDP-43 with progranulin can further affect the angiogenesis in ALS patients by regulating activity of VEGF receptors, but conclusive evidence is needed to establish its role in pathogenesis of ALS. Certain mutations in UBQLN2 and UBQLN4 indicate that ubiquitination has a role in ALS pathobiology, but its link to angiogenesis has not been adequately studied. Recent studies have shown that several mutations in RNA-binding proteins (RBPs) can also cause ALS. Conclusively, in this review, we have attempted to argue the role of angiogenesis in enhanced ALS survival rate is probably regulated with the activation of NF-κß. Additionally, interaction between OPTN and TDP-43 can also impact the transcription of various angiogenic molecules. Whether targeting angiogenic substances or TDP-43 can provide clues about extending ALS survival rate, in combination with current treatments, can only be evaluated after additional studies.

Allium cepa exerts neuroprotective effect on retinal ganglion cells of pterygopalatine artery (PPA) ligated mice.

BACKGROUND: Repeated failure to rescue the damaged retinal ganglion cells (RGCs) by various drugs has warranted the need to screen common herbal compounds available in the form of various eye formulations for their efficacy. OBJECTIVE: We aimed to investigate the neuroprotective effect of pretreatment with aqueous extract of A. cepa in Ischemia/Reperfusion (I/R) induced retinal injury. METHODS: Ischemia was induced for 2 h by pterygopalatine artery (PPA) ligation in C57BL/6J mice, followed by reperfusion. The neuroprotective role of oral pretreatment with aqueous extract of A. cepa (300 mg/kg) was analyzed with respect to control and injury only group at 7, 14, and 28 day after the surgery for expression of different genes in the retina by Real-Time PCR. RESULTS: Molecular analysis at different time points showed increased expression of BCl-2, GDNF, GFAP, and Brn3b in the retina at 14 and 28 day after A. cepa treatment in comparison to the injury alone group. However, at shorter time point (7th day), the expression of these genes was pronounced in the injury only group in comparison to the injury and pretreated group. CONCLUSION: Pretreatment with aqueous extract of A. cepa may protect from the neuronal damage in I/R-induced retinal injury in mice by altering the expression of neurotrophic factor.

Effectiveness of Yoga as the Public Health Intervention Module in the Management of Diabetes and Diabetes Associated Dementia in South East Asia: A Narrative Review.

BACKGROUND: Diabetes mellitus (DM) is widely spread in South Asian (ASEAN) and Indian sub-continent. The increasing healthcare costs of DM can be prevented in the developing world by improved public healthcare interventions. Modifiable risk factors of DM like sedentary lifestyle, obesity, and stressful conditions are associated with its progression; however, the epidemiological data collected by Public Institutions are limited. SUMMARY: A review of published literature describing geographic distribution of DM and associated dementia in South Asian region, particularly India, was conducted with the purpose of assessing the feasibility and challenges associated with the Yoga-based risk reduction. PubMed and Google Scholar databases were searched for DM and dementia-related articles by using a combination of keywords: Diabetes, Diabetes related Dementia Southeast Asia, Pre-diabetes, Yoga, lifestyle modification, Dementia and Exercise. The epidemiological data generated from these diseases have not prompted to any major public health policies. Yoga can be a cost-effective intervention for the prevention of Type 2 DM (T2DM) and its associated cognitive decline when detected early. If nationwide intervention of Yoga is brought about by the state, its integration in health care will become more meaningful and acceptable. Key Message: Studies suggest that Yoga and change in lifestyle can modify the health risks associated with T2DM and associated dementia if it is mainstreamed with the public health initiative of Ayushman Bharat scheme.

Altered Expression of Heat Shock Protein-27 and Monocyte Chemoattractant Protein-1 after Acute Spinal Cord Injury: A Pilot Study.

Background Spinal cord injury (SCI) leads to serious complications involving primary trauma and progressive loss due to inflammation, local ischemia, or infection. Despite a worldwide annual incidence of 15 to 40 cases per million, methylprednisolone is the only treatment available to alleviate neurologic dysfunction; therefore, research is currently focused on identifying novel targets by biochemical and molecular studies. Purpose Here, we investigated the expression of various molecular markers at the messenger ribonucleic acid (mRNA) and protein level at day 0 and day 30 post-SCI. Methods Enzyme-linked immunosorbent assay (ELISA) was performed to determine the expression of CASPASE-3 and heat shock protein-27 (HSP-27) in serum samples. Real-time polymerase chain reaction (RT-PCR) was performed to determine the level of mRNA expression of vascular endothelial growth factor receptor-1 (VEGFR-1), VEGFR-2, HSP-27, monocyte chemoattractant protein-1 (MCP-1), and CASPASE-3. Results HSP-27 expression at day 30, as compared with day 0, showed significant downregulation. In contrast, there was elevated expression of MCP-1. ELISA analysis showed no significant change in the expression of CASPASE-3 or HSP-27. Conclusion There may be possible opposing role of HSP-27 and MCP-1 governing SCI. Their association can be studied by designing in vitro studies.

Partitioning of radiological, stress and biochemical changes in pre-diabetic women subjected to Diabetic Yoga Protocol.

BACKGROUND: Yoga is an ancient system of wellness with Asana and Pranayama as its most popular and propagated modules for management of lifestyle disorders. OBJECTIVES: The aim of the study was to characterise the liver abnormalities, biochemical changes, and stress levels after Yoga intervention in prediabetic females. MATERIALS AND METHODS: 37 females were randomly divided into Yoga practising and non-practising control groups. The Yoga practising group performed Diabetic Yoga Protocol (DYP) for 3 months. Parameters including size of liver, fatty infiltration, and grade of severity were measured using ultrasonography along with biochemical parameters and stress levels at baseline and after Yoga practice. RESULTS: The glycosylated hemoglobin (HbA1c) and glucose levels were found significantly reduced in prediabetic (p = 0.015) women after practising DYP, although cholesterol levels increased in menopausal women. No escalation of fatty liver was noted among women practising DYP. CONCLUSION: DYP reduced the HbA1c and stress levels and therefore, could be a cost-effective tool for preventing prediabetes to diabetes progression.

Human Fetal Pigmented Ciliary Epithelium Stem Cells have Regenerative Capacity in the Murine Retinal Degeneration Model of Laser Injury.

BACKGROUND: Retinal degeneration and related eye disorders have limited treatment interventions. Since stem cell therapy has shown promising results, ciliary epithelium (CE) derived stem cells could be a better choice given the fact that cells from eye niche can better integrate with the degenerating retina, rewiring the synaptic damage. OBJECTIVE: To test the effect of human fetal pigmented ciliary epithelium-derived neurospheres in the mouse model of laser-induced retinal degeneration. METHODS: C57 male mice were subjected to retinal injury by Laser photocoagulation. Human fetal pigmented ciliary epithelium was obtained from post-aborted human eyeballs and cultured with epidermal growth factor (rhEGF) and fibroblast growth factor (rhFGF). The six day neurospheres were isolated, dissociated and transplanted into the subretinal space of the laser injured mice at the closest proximity to Laser shots. Mice were analyzed for functional vision through electroretinogram (ERG) and sacrificed at 1 week and 12 week time points. Retinal, Neurotropic, Apoptotic and proliferation markers were analysed using real-time polymerase chain reaction (PCR). RESULTS: The CE neurospheres showed an increase in the expression of candidate genes analyzed in the study at 1 week time point, which sustained for longer time point of 12 weeks. CONCLUSION: We showed the efficacy of human CE cells in the regeneration of retinal degeneration in murine model for the first time. CE cells need to be explored comprehensively both in disease and degeneration.

Alpha lipoic acid attenuates the long-term effects of lead exposure in retinal ischemic injury mouse model.

Lead (Pb) exposure is reported to be unsafe for humans. There have been several studies documenting acute and chronic Pb toxicity on the organ systems. New studies suggest that early-life exposure to such environmental toxins may increase the susceptibility to late-onset degenerative disorders. We aimed to examine the long-term effects of early-life postnatal exposure of Pb on retinal degeneration. Pb exposure (200 ppm) was provided either at postnatal day 1 through lactation (early-life exposure) or at 7th week of age (adulthood exposure) directly through drinking water for 20 days. The Pb-treated mice were followed till 20 weeks of age. At 20th week, ischemia/reperfusion (I/R) injury was induced in these mice by pterygopalatine artery ligation. Further, alpha lipoic acid (ALA) was administered to examine its neuroprotective effects against retinal damage. Histological and molecular analysis revealed that Pb-treated mice had greater retinal damage after I/R injury as compared to untreated or ALA treated mice, suggesting that ALA protects the early-life Pb exposure and its consequent impact on later life. The elevated levels of glial derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) and reduced levels of glial fibrillary acidic protein (GFAP) upon ALA pre-treatment suggest that it probably exerts anti-inflammatory effects via upregulation of neurotrophic factors.

Guinness world record attempt as a method to pivot the role of Yoga in Diabetes management.

BACKGROUND: Attempts for Guinness world record have continued worldwide but these attempts were rarely aimed to promote public health. Diabetes is one of the rapidly growing lifestyle disorders in India which requires awareness reinforcements among the local population. In recent studies, Yoga has proved to be useful in lifestyle modification and Diabetes management. However, most individuals from rural and urban localities in the country are unaware of this fact. PURPOSE: The purpose was to organizing a nationwide attempt under the Niyantrit Madhumeh Bharat (NMB) programme to break the world record to be the largest Diabetes lesson, to spread awareness among general population. METHODS: Present article represents the perspective of the Chandigarh chapter of NMB programme and its experience in Guinness world record attempt. Diabetes awareness lesson was organized in the city as per the standards defined by the Guinness Book and outcomes of the entire campaign were assessed at the end of the campaign. RESULT: Total 498 individuals participated in the campaign. Among them, 268 participants were questioned at the end of the campaign about the role of Yoga in Diabetes. 247 participants (92%) were agreed that Diabetes can be modified by Yoga and 9 participants (3%) disagreed. The remaining 12 participants (5%) did not give any response. CONCLUSION: We noticed that most of the participants became aware of the role of Yoga in Diabetes.

Creating a role model for "Academicians" Social Responsibility (ASR) synergizing with Swachh Bharat Abhiyaan: A campus hygiene initiative by PGIMER, Chandigarh.

BACKGROUND: The state of disarray from unhygienic conditions and excessive litter throughout urban highways, alleyways, and byways across rural and urban localities of India is abysmal. Such unsanitary conditions impinge upon the future health and welfare of its citizens, tourists and economic development. PURPOSE: The NRL volunteered PGIMER's campus hygiene initiative" is a pioneering effort spearheaded in compliance with Indian Prime Minister's call that citizens of India work together to establish a cleaner and healthier environment. METHODS: A group of 15 highly motivated students in the Neuroscience Division of the PGIMER, worked together vigorously 2 hours a week to affect a cleaner urban environment in the city. RESULT: The results were national Kayakalp and Skoch award to PGIMER as the cleanest hospital in the country, the vendors or patients no longer litter around the campus, the pot holes have been converted into greener patches, signs board adorn the campus. CONCLUSION: To inspire citizens through faculty- student led sanitation programs.

Nobel Nominations in Science: Constraints of the Fairer Sex.

Nobel Prize is the highest honor in the scientific community that is bestowed for the contribution of eminent scientists in various spheres of science. Since its inception in 1901, many renowned scientists have received this award. However, when compared to men, women's share as recipients is abysmally low. Although the contribution of female scientists has tremendously increased in the last few decades, yet the lack of proportionate increase in recognition is conspicuous by its disproportionate number of women recipients. This paper addresses this issue and underlines some of the reasons contributing to an underrepresentation of women scientists among Nobel Laureates.

Early Life Pb Exposure and its Effect on Later Life Retinal Degeneration.

The study presents the longitudinal effect of early life lead exposure on retinal ischemia. Swiss albino mice were exposed to lead acetate at two different timepoints viz. postnatal day 1-20 and at 7th week of age. These mice were then followed till 10 week of age and subjected to retinal ischemia. Retinal ischemia was induced using pterygopalatine artery ligation. The effect of prior lead exposure on ischemic insult was determined using various histological and molecular parameters. Although toxic effects of Pb are well reported, but the results in this study showed not much significant effect of early life Pb exposure on later life retinal degeneration. While retinal thickness was decreased in surgery group and 7th week Pb exposed group, PND Pb exposed mice showed retinal thickness comparable to normal control. There was no difference in TUNEL positive cells in Pb exposed group when compared to surgery group. The molecular studies revealed overexpression of BDNF and GFAP in PND Pb exposed mice reflecting more injury and inflammation. The combined results revealed that Pb exposure have mild effect on overall susceptibility to retinal damage in later life. The Pb may exert its toxic effects at longer duration and thus the toxic effects may be mapped at longer timepoints. The study provides a new dimension to the already well known toxic effects of lead which needs to be further explored. J. Cell. Biochem. 118: 3213-3224, 2017. © 2017 Wiley Periodicals, Inc.