Gangadhar Bhurle’s research while affiliated with National Institute of Pharmaceutical Education And Research Ahmedabad and other places

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Publications (2)


Stroke in Pregnancy Brings Epigenetic Changes in Correlation with Affected Mitochondrial Dynamics and Inflammasome Mediated Apoptosis in Rodents
  • Article

May 2025

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12 Reads

Journal of the American Heart Association

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Dipali Rahane

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Gangadhar Bhurle

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[...]

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Pallab Bhattacharya

Background Pregnancy may be a risk factor for stroke in females. Stroke in pregnancy influences mitochondrial dynamics as well as the inflammatory responses in mothers. However, limited studies are available that report any epigenetic changes in the offspring following a stroke in mothers. In the present study we investigate the effect of stroke in pregnancy as a possible epigenetic modifier correlated with dysfunctional mitochondrial dynamics and exacerbated inflammasome mediated apoptosis in the offsprings. Methods and Results Female and male Sprague Dawley rats were housed in the same cage in 1:2 ratio to ensure successful pregnancy. Stroke was induced by middle cerebral artery occlusion at gestational day 17. After delivery of F1 generation, bloods were collected from the dams for hormonal study. Brains were harvested from both dams and F1 generation for biochemical, histological, genetic, molecular, and mitochondrial studies. In the F1 generation of stroke induced dams, an increased mitochondrial fission and decreased mitochondrial fusion were observed as compared with normal dams and their F1 generation. Similarly, enhanced mitochondrial reactive oxygen species and depolarization were also observed in the F1 generation of stroke induced dams. Exacerbated inflammasome signaling and enhanced apoptosis were also evident in this F1 generation. Changes in histone‐methylation corresponding to increased inflammation were also observed in this F1 generation. Conclusions The present study reports the occurrence of epigenetic modifications towards mitochondrial dysfunction and exacerbated inflammasome mediated apoptosis in the F1 generation following a stroke in pregnant dams.


A mechanistic approach of major comorbidities associated with stroke. Hyperglycemia, hyperlipidemia, hypertension, and atherosclerotic disorders can result in an aggravated stroke outcome individually or in combination. Hypertension leads to increased reactive oxygen species (ROS) generation and upregulation of various inflammatory cytokines (such as, tumor necrosis factor‐α, interleukin‐6/1β, interferon‐γ, C‐reactive protein, elastase, lipoprotein A, intercellular adhesion molecule, E‐selectin, etc.). Inflammatory markers can also be secreted due to hyperglycemia‐mediated acidotoxicity. On the other hand, hyperlipidemia‐mediated plaque disposition in the arterial intima results in atherosclerosis. When the plaque dislodges, it can block cerebral blood vessels and result to ischemic stroke. Similarly, hypertensive disorders facilitate ischemic stroke via clogging of blood vessels and hemorrhagic stroke following excessive increase of shear stress on the vessel resulting to arterial malformation. Post‐stroke neuroinflammation activates various matrix metalloproteinase (MMPs) leading to blood–brain‐barrier (BBB) disruption. As a result, infiltration of excessive leukocyte, pathogen, and fluid results in edema generation. BBB, blood–brain barrier; CRP, C‐reactive protein; ICAM, intercellular adhesion molecule; IFN, interferon; IL, interleukin; MMP, matrix metalloproteinase; TNF, tumor necrosis factor.
A mechanistic approach of minor comorbidities associated with stroke. In chronic kidney disease (CKD), endothelial glomerular filtration rate (eGFR) decreases due to different predisposed factors leading to uremia. In the brain, uremia results in disruption of the blood–brain barrier (BBB) due to increased oxidative stress, excessive chemokine secretion from activated microglia, endothelial damage, activation of coagulation cascade and the Von Willbrand factor, leading to thrombus formation. Astrocytes and neurons in the brain activate the local renin–angiotensin aldosterone system (RAAS) system and produce angiotensin‐II (Ang‐II) through the angiotensin‐converting enzyme (ACE). Ang‐II binds to the angiotensin II receptor type 1 (AT1) receptor resulting in vasoconstriction and arterial stiffness and finally ischemic stroke. On the other hand, endothelial damage leads to low‐density lipoprotein (LDL) deposition and atherosclerosis‐mediated ischemic stroke. In cancer, various pathogens invade the systemic circulation due to compromised host immunity which can stimulate tissue factors and platelets as the coagulation cascade gets activated and results in ischemic stroke. Atrial fibrillation decreases endothelial nitric oxide synthase (eNOS) generation and nitric oxide (NO) formation in the cardiomyocyte which leads to clot formation and easy arterial clogging. In sickle cell disease, along with decreased NO formation, excessive generation of different cytokines and interleukins leads to ischemic stroke predisposition. Coronavirus disease 2019 (COVID‐19), cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL), and neurosyphilis can also alter clotting cascade and result in ischemic stroke. On the other hand, Moyamoya disease and some forms of cancer can lead to malformation of vessels leading to unwanted rupture and hemorrhagic stroke.
Stroke and associated comorbidities in Southeast Asian countries
  • Article
  • Full-text available

January 2025

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70 Reads

Stroke, a leading cause of mortality and morbidity worldwide, is a complex cerebrovascular disease. Stroke risk factors are diverse, encompassing age, sex, and ethnicity. Comorbid conditions, including hypertension, hyperglycemia, hyperlipidemia, and atrial fibrillation, exacerbate stroke outcomes, contributing to the overall stroke burden within populations. In addition to these factors, lifestyle‐related diseases can impact individuals across all age groups, and often include as comorbidities linked to stroke. Socioeconomic conditions, healthcare access, and the quality of clinical data significantly influence the prevalence of comorbidities. Asia, the largest continent and home to 60% of the world's population, includes many developing nations undergoing diverse economic transitions. In Southeast Asian countries, stroke prevalence is high, imposing a substantial burden on healthcare systems and economies. Research disparities in stroke are often attributed to insufficient demographic data on comorbidities. Hence, the review discusses all previously published results of hospital‐based studies and data from national registries. It has been noticed that due to insufficient documentation on stroke‐related comorbidities in various developing countries of Southeast Asia, stroke management becomes difficult. Therefore, this review aims to discuss the association between various comorbidities and stroke, with special emphasis on the incidence and prevalence of stroke burden in Southeast Asian countries.

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