Biology subjects

Gunaseelan, D.

Publications and source records attributed to Gunaseelan, D..

3 recordsLinked to original sources

bioRxiv2023

Short-term intermittent hypoxia therapy promotes gliogenesis in a rat model of middle cerebral artery occlusion (MCAO) stroke

AimAfter focal cerebral ischemia, intermittent hypoxia therapy (IHT) could be used as a non-invasive method to stabilize and stimulate neurogenesis in the innate stem cell niche in the brain, and disrupt the glial scar around the infarct to increase neuroblast migration in the striatal infarct area. MethodsWe induced focal cerebral ischemia in Wistar albino rats using the MCAo model. A week later, animals were subjected to intermittent hypoxia (12%O2, 4hr/day) for a period of 14 days. Post-treatment analysis of functional recovery and cellular regeneration was done using immunofluorescence analysis of multiple neuronal cell markers including Doublecortin (DCX), Nestin, and Vimentin among others. ResultsObservations of GFAP-positive cells revealed that IH treatment facilitates gliogenesis in the infarct striatal region of a rat model of MCAo stroke. The percentage of DCX and GFAP double-positive cells was increased in the IH-treated group. Also, there was a significant difference in the morphology of vimentin-positive cells and microglia cells between the stroke groups. ConclusionThese outcomes suggest that exposure of MCAo stroke-affected rats to intermittent hypoxia results in an increase in migrated neuroblasts resulting in a subsequent altered glial scar integrity in the infarct region, thus suggesting an alternative non-invasive method against the common stem cell transplant techniques, to increase endogenous neuroblasts in the infarct area after stroke.

neuroscience↗

bioRxiv2021

Altered neurogenic pathways in experimental rat models of ischemic cerebral stroke: A transcriptome based meta-analysis

1)ObjectivesPromoting neurogenesis mediated recovery is one of the most sought after strategies in recovery after cerebral stroke. In this paper we elucidate how neurogenesis related genes are altered in the early stroke environment, to hint at potential pathways for therapeutic recovery. Materials and MethodsAround 97 microarray datasets derived from stroke affected rat brains were collected from NCBI-GEO. Datasets were normalized and subjected to meta-analysis in Network Analyst to identify differentially expressed genes. Gene enrichment analyses were carried out using GSEA, and WebGestalt, and results were visualized using Cytoscape Enrichment mapping. ResultsNearly 939 differentially expressing genes were identified in the cerebral stroke group. Among them 30 neurogenesis related genes were identified through enrichment mapping analysis, and 35 genes through Protein- Protein Interaction analysis. Highest upregulated neurogenesis genes were found to be TSPO, GFAP, VIM, and TGFB1. Highest Downregulated neurogenesis genes were found to be THY1, NR1D1, CDK5, STX1B, and NOG. ConclusionsThrough this study, we have identified that during the acute time frame after stroke, majority of the neurogenesis genes related to neural proliferation and neural differentiation are downregulated, while the majority of the genes related to neuronal migration were upregulated. Single or combined therapeutic approach against the identified dysregulated genes could greatly aid neural restoration and functional recovery during the postischemic stage.

neuroscience↗

bioRxiv2019

Islet macrophages drive islet remodeling and compensatory hyperinsulinemia in the early diabetes

{beta}-cells respond to peripheral insulin resistance by increasing circulating insulin in early type-2 diabetes (T2D). Islet remodeling supports this compensation but the drivers of this process remain poorly understood. Infiltrating macrophages have been implicated in late stage T2D but relatively little is known on islet resident macrophages, especially in early T2D. We hypothesize that islet resident macrophages contribute to islet vascular remodeling and hyperinsulinemia, the failure of which results in a rapid progression to T2D. Using genetic and diet-induced models of compensatory hyperinsulinemia we show that its depletion significantly compromises islet remodeling in terms of size, vascular density and insulin secretion capacity. Depletion of islet macrophages reduces VEGF-A secretion from both human and mouse islets ex vivo and the impact of reduced VEGF-A functionally translates to delayed re-vascularization upon transplantation in vivo. Hence, we show a new role of islet resident macrophages in the context of early T2D and suggest that there is considerable utility in harnessing islet macrophages to promote islet remodeling and islet insulin secretion capacity.\n\nHighlightsO_LIThe compensatory hyperinsulinemic phase of type-2 diabetes is accompanied with significant pancreatic islet remodeling.\nC_LIO_LIBona fide islet resident macrophages are increased during the diabetic compensation phase by largely in situ proliferation.\nC_LIO_LIAblating macrophages severely compromises the islet remodeling process and exacerbates glycemic control in vivo.\nC_LIO_LIMouse and human islet macrophages contribute VEGF-A to the islet environment.\nC_LIO_LISpecific removal of islet macrophages delays islet vascularization in compensatory hyperinsulinemic mice.\nC_LI

molecular biology↗