ISBRA Featured Publications
At ISBRA, our mission is to promote research and knowledge sharing among young researchers worldwide. We are proud to showcase the work of our students and researchers in top-tier publications, covering a wide range of topics in the fields of science, technology, engineering, and mathematics. Browse our collection of publications and stay up-to-date with the latest research trends and insights.
Evaluating Pain Behaviours: Widely Used Mechanical and Thermal Methods in Rodents
Globally, over 300 million surgical procedures are performed annually, with pain being one of the most common post-operative side effects. During the onset of injury, acute pain plays a protective role in alerting the individual to remove noxious stimuli, while long-lasting chronic pain without any physiological reason is detrimental to the recovery process. Hence, it created an urgent need to better understand the pain mechanism and explore therapeutic targets. Despite the hardship in performing human pain studies due to ethical considerations, clinically relevant rodent pain models provide an excellent opportunity to perform pain studies. Several neurobehavioural tests are used to assess the drug efficacy in rodents to determine avoidance behaviour latency and threshold. This review article provides a methodological overview of mechanical (i.e. von Frey, Mechanical Conflict System) and thermal (i.e. Hargreaves Assay, Hot and Cold Plate, Temperature Place Preference) tests to assess pain in clinically relevant pain rodent models. We further discussed the current modifications of those tests along with their use in literature, the impact of confounding variables, advantages and disadvantages.
Comparing Monopharmacotherapy of Antiarrhythmic and Anticoagulant Drugs with Other Drugs for Atrail Fibrillation: A Complete Review of Clinical Trails
Atrial fibrillation (AF) is a life‐changing and life‐threatening cardiac electropathological condition, especially in patients with prior history of cardiovascular diseases. This multifaceted condition is one of the top 5 leading causes of cardiovascular death with a rapidly increasing prevalence and death rate. From inception till now, numerous clinical trials have been conducted to explore novel therapeutic targets and strategies along with pre‐existing treatments for patients suffering from atrial fibrillation. The pharmacotherapy approach to treat AF (acute, chronic, persistent, paroxysmal, non‐valvular, nonrheumatic, and rapid) comprises mainly antiarrhythmic drugs (AAD) and anticoagulant drugs (ACD) for rate and rhythm control along with the prevention of strokes. This narrative review aims to discuss monotherapeutic clinical trials that compared AADs (class II: carvedilol and xamoterol; class III: amiodarone; class IV: verapamil, diltiazem, and nifedipine) and ACDs (vitamin K antagonist: warfarin; factor Xa inhibitor: apixaban; factor IIa and Xa inhibitor: heparin) with cardiac glycoside (digoxin), angiotensin II receptor antagonist (telmisartan), platelet inhibitor (indobufen), anti‐ convulsant (magnesium sulfate), anti‐inflammatory (aspirin), and antipyretic drugs (aspirin) to treat various types of AF in patients with a diverse history of cardiovascular diseases. This study provides a review of all clinical trials on this topic and provides a comparative chart for healthcare professionals to determine the best‐ suited treatment for their patients
The Role of Akt Signalling Pathway in Neurological and Cardiovascular Pathologies
The PI3K/Akt/mTOR signalling pathway plays a crucial role in several biological processes, including cell proliferation, survival, and apoptosis, as well as regulates numerous signalling pathways, including JNK, NF-𝜅B, and ERK pathways. The recent proliferation of signal transduction studies in neurological and cardiovascular diseases/injuries sheds light on Akt-dependent pathogenesis. The downregulation of the Akt signalling pathway 24 hours post-injury prevents neurogenesis and promotes the progression of severe secondary injuries, including neuroinflammation, scar formation, and neuronal and glial necrosis, following traumatic brain and spinal cord injury, suggesting designing therapeutic approaches within a 24-hour window postinjury. Similarly, the downregulation of the Akt signalling pathway in myocardial infarction lowers cardiovascular protection, limits neurovascularization, and inhibits cell survival. Following myocarditis, the Akt signalling network is upregulated, leading to aggravated inflammation, and increased myocardial damage. Also, the upregulation of the PI3K/Akt/mTOR pathway in chordoma promotes tumor progression and invasion, leading to neuronal damage and impaired physiological functions. Future therapeutics that target the aberrant expression of key players in the PI3K/Akt/mTOR signalling pathway present a promising approach to treating several neurological and cardiovascular pathologies. This narrative review discusses the role of PI3K/Akt/mTOR signalling pathway in traumatic central nervous system injuries (brain and spinal cord), cardiac injury (myocardial infarction), inflammatory disease (myocarditis), and rare neurological cancer (chordoma) along with therapeutic targets that are known to prevent worsened outcomes and promote recovery following those conditions.
KCCs, NKCCs, and NCC: Potential targets for cardiovascular therapeutics? A comprehensive reivew of cell and region specific expression and function
Cardiovascular diseases, the leading life-threatening conditions, involve cardiac arrhythmia, coronary artery disease, myocardial infarction, heart failure, cardiomyopathy, and heart valve disease that are associated with the altered functioning of cation-chloride cotransporters. The decreased number of cation-chloride cotransporters leads to reduced reactivity to adrenergic stimulation. The KCC family is crucial for numerous physiological processes including cell proliferation and invasion, regulation of membrane trafficking, maintaining ionic and osmotic homeostasis, erythrocyte swelling, dendritic spine formation, maturation of postsynaptic GABAergic inhibition, and inhibitory/excitatory signaling in neural tracts. KCC2 maintains intracellular chlorine homeostasis and opposes β-adrenergic stimulation-induced Cl- influx to prevent arrhythmogenesis. KCC3-inactivated cardiac tissue shows increased vascular resistance, aortic distensibility, heart size and weight (i.e. hypertrophic cardiomyopathy). Due to KCC4's high affinity for K+, it plays a vital role in cardiac ischemia with increased extracellular K+. The NKCC and NCC families play a vital role in the regulation of saliva volume, establishing the potassium-rich endolymph in the cochlea, sodium uptake in astrocytes, inhibiting myogenic response in microcirculatory beds, regulation of smooth muscle tone in resistance vessels, and blood pressure. NKCC1 regulates chlorine homeostasis and knocking it out impairs cardiomyocyte depolarization and cardiac contractility as well as impairs depolarization and contractility of vascular smooth muscle rings in the aorta. The activation of NCC in vascular cells promotes the formation of the abdominal aortic aneurysm. This narrative review provides a deep insight into the structure and function of KCCs, NKCCs, and NCC in human physiology and cardiac pathobiology. Also, it provides cell-specific (21 cell types) and region-specific (6 regions) expression of KCC1, KCC2, KCC3, KCC4, NKCC1, NKCC2, and NCC in heart.