Review Article
Volume 5 Issue 8 - 2022
Stress: Its Mechanism, Experimental Assessment and Diagnostic Markers

Mohd Rafi Reshi1*, Nusrat Nabi1, Afshana Bashir Reshi2, Aabida Majid3, Saman Anees4, Nafaa Hasan1, Maaz Naqvi1 and Jamal Akhtar5

1Department of Pharmacology Hamdard Institute of Medical Sciences and Research, Jamia Hamdard University, New Delhi India

2DRDO Associated Hospital, Government Medical College, Srinagar, Jammu and Kashmir, India

3Government Amt School Shireenbagh, Govt. Medical College, Srinagar, Jammu and Kashmir, India

4Department of Amraze Niswan Wa Atfal, SUMER, Jamia Hamdard University New Delhi, India

5Cetral Council for Research in Unani Medicine, Janikpuri, New Delhi, India

*Corresponding Author: Mohd Rafi Reshi, Department of Pharmacology Hamdard Institute of Medical Sciences and Research, Jamia Hamdard University, New Delhi India.
Received: July 28, 2022; Published: August 18, 2022


Stress is linked to the central nervous system. In addition to its primary function in the body, it also assists in body upkeep. As a result, its proper operation is critical for both health and sickness. When the central nervous system is out of equilibrium, the CNS system's mechanism changes. Understanding the mechanism of stress is crucial for developing pharmaceutical methods for its prevention. Among the common molecular pathways contributing to impaired brain function are inflammation, immunomodulation and oxidative stress. A variety of drugs and chemicals are used to experimentally induce stress of CNS, which are assessed in the laboratory by physiological, physically, emotionally and pathological biomarkers. The present review outlines some of the fundamental ideas in stress, as well as several preclinical screening methodologies and diagnostic markers.


Keywords: Stress; Brain; Markers; Diseases


  1. Chauhan NS., et al. “Studies on antistress activity of Curculigo Orchioides gaertn”. Biomedical and Biotechnology Research Journal 5 (2021): 145-148.
  2. Selye H. “The stress of life”. Mc Graw Hill Books, New York 1950 (2007): 1-11.
  3. Synle S. “Guide to stress research”. Von Nostrand, New York (1976): 22-27.
  4. Meera S and Chowdary GN. “Antistress And Immunomodulatory Activity of Aqueous Extract of Momordica charantia”. Pharmacognosy Magazine 19 (2009): 69-73.
  5. Meaney MJ and Szyf M. “Environmental programming of stress responses through DNA methylation: life at the interface between a dynamic environment and a fixed genome”. Dialogues in Clinical Neuroscience 7 (2005): 103-123.
  6. Hunter RG., et al. “Stress and the dynamic genome: Steroids, epigenetics, and the transposome”. Proceedings of the National Academy of Sciences of the United States of America (2014).
  7. Bruce SM., et al. “Mechanisms of stress in the brain”. Nature Neuroscience 10 (2015): 1353-1363.
  8. Hill MN and McEwen BS. “Involvement of the endocannabinoid system in the neurobehavioural effects of stress and glucocorticoids”. Progress in Neuro-Psychopharmacology and Biological Psychiatry (2009).
  9. Szyf M., et al. “Maternal programming of steroid receptor expression and phenotype through DNA methylation in the rat”. Frontiers in Neuroendocrinology 26 (2005): 139-162.
  10. McGowan PO., et al. “Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse”. Nature Neuroscience 12 (2009): 241-243.
  11. Rao RP., et al. “Glucocorticoids protect against the delayed behavioral and cellular effects of acute stress on the amygdala”. Biological Psychiatry 72 (2012): 466-475.
  12. Zohar J., et al. “High dose hydrocortisone immediately after trauma may alter the trajectory of PTSD: interplay between clinical and animal studies”. European Neuropsychopharmacology 21 (2011): 796- 809.
  13. Schelling G., et al. “Can posttraumatic stress disorder be prevented with glucocorticoids?” Annals of the New York Academy of Sciences 1032 (2004): 158-166.
  14. Mitra R and Sapolsky RM. “Acute corticosterone treatment is sufficient to induce anxiety and amygdaloid dendritic hypertrophy”. Proceedings of the National Academy of Sciences of the United States of America 105 (2008): 5573-5578.
  15. Pawlak R., et al. “Tissue plasminogen activator and plasminogen mediate stress-induced decline of neuronal and cognitive functions in the mouse hippocampus”. Proceedings of the National Academy of Sciences of the United States of America 102 (2005): 18201-18206.
  16. Chen Y., et al. “Cellular and molecular mechanisms of hippocampal activation by acute stress are age-dependent”. Molecular Psychiatry 11 (2006): 992-1002.
  17. Bennur S., et al. “Stress-induced spine loss in the medial amygdala is mediated by tissue plasminogen activator”. Neuroscience 144 (2007): 8-16.
  18. Matys T., et al. “Tissue plasminogen activator promotes the effects of corticotropin releasing factor on the amygdala and anxiety-like behavior”. Proceedings of the National Academy of Sciences of the United States of America 101 (2004): 16345-16350.
  19. Mucha M., et al. “Lipocalin-2 controls neuronal excitability and anxiety by regulating dendritic spine formation and maturation”. Proceedings of the National Academy of Sciences of the United States of America 108 (2011): 18436-18441.
  20. Skrzypiec AE., et al. “Stress-induced lipocalin-2 controls dendritic spine formation and neuronal activity in the amygdala”. PLoS One 8 (2013): e61046.
  21. File SE. “Factors controlling measures of anxiety and responses to novelty in the mouse”. Behavioural Brain Research 125 (2001): 151-157.
  22. Blanchard DC., et al. “The Mouse Defense Test Battery: pharmacological and behavioral assays for anxiety and panic”. European Journal of Pharmacology 463 (2003): 97-116.
  23. Wood GE., et al. “Acute and chronic restraint stress alter the incidence of social conflict in male rats”. Hormones and Behavior 43 (2003): 205-213.
  24. Sanchez C. “Stress-induced vocalisation in adult animals. A valid model of anxiety”. European Journal of Pharmacology 463 (2003): 133-143.
  25. Hofer MA. “Multiple regulators of ultrasonic vocalization in the infant rat”. Psychoneuroendocrinology 21 (1996): 203-217.
  26. Conrad CD., et al. “Support for a bimodal role for type II adrenal steroid receptors in spatial memory”. Neurobiology of Learning and Memory 72 (1999): 39-46.
  27. Sgoifo A., et al. “Effects of sleep deprivation on cardiac autonomic and pituitary-adrenocortical stress reactivity in rats”. Psychoneuroendocrinology 31 (2006): 197-208.
  28. Amit Z and Galina ZH. “Stress-induced analgesia: adaptive pain suppression”. Physiological Reviews 66 (1986): 1091-1120.
  29. Olivier B., et al. “Stress-induced hyperthermia and anxiety: pharmacological validation”. European Journal of Pharmacology 463 (2003): 117-132.
  30. Corwin RL and Buda-Levin A. “Behavioral models of binge-type eating”. Physiology and Behavior 82 (2004): 123-130.
  31. Vladimir KP and Alexandre VP. “Experimental models of stress”. Dialogues in Clinical Neuroscience 8 (2006): 417-432.
  32. Josko J. “Liberation of thyreotropin, thyroxine and triiodothyronine in the controllable and uncontrollable stress and after administration of naloxone in rats”. The Indian Journal of Physiology and Pharmacology 47 (1996): 303-310.
  33. Van de Kar LD and Blair ML. “Forebrain pathways mediating stress-induced hormone secretion”. Frontiers in Neuroendocrinology 20 (1999): 1-48.
  34. Jung ME., et al. “The discriminative stimulus effects of pentylenetetrazol as a model of anxiety: recent developments”. Neuroscience and Biobehavioral Reviews 26 (2002): 429-439.
  35. Pechnick RN. “Effects of opioids on the hypothalamo-pituitary-adrenal axis”. Annual Review of Pharmacology and Toxicology 33 (1993): 353-382.
  36. Skaper SD and Giusti LFP. “Neuroinflammation, microglia and mast cells in the pathophysiology of neurocognitive disorders: a review”. CNS and Neurological Disorders (2014): 1654-1666.
  37. Zafar T. “Potential biomarkers of emotional stress induced neurodegeneration”. Neurological Sciences 21 (2020): 100292.
  38. Audet MC., et al. “Social defeat promotes specific cytokine variations within the prefrontal cortex upon subsequent aggressive or endotoxin challenges”. Brain, Behavior, and Immunity 25 (2001): 1197-1205.
  39. Simpson RJ., et al. “Interleukin-6: structure-function relationships”. Protein Science 6 (1997): 929-955.
  40. Hodes GE., et al. “Integrating Interleukin-6 into depression diagnosis and treatment”. Neurobiology of Stress 4 (2016): 15-22.
  41. Pollak Y and Yirmiya R. “Cytokine-induced changes in mood and behaviour: implications for ‘depression due to a general medical condition’, immunotherapy and antidepressive treatment”. The International Journal of Neuropsychopharmacology 5 (2002): 389-399.
  42. Fiedorowicz JG., et al. “Peripheral inflammation during abnormal mood states in bipolar I disorder”. Journal of Affective Disorders 187 (2015): 172-178.
  43. Feyissa AM., et al. “Reduced levels of NR2A and NR2B subunits of NMDA receptor and PSD-95 in the prefrontal cortex in major depression”. Progress in Neuro-Psychopharmacology and Biological Psychiatry 33 (2009): 70-75.
  44. Kirschbaum C and Hellhammer DH. “Salivary cortisol in psychoneuroendocrine research: recent developments and applications”. Psychoneuroendocrinology 19 (1995): 313-333.
  45. Hoifodt RS., et al. “Cortisol levels and cognitive profile in major depression: a comparison of currently and previously depressed patients”. Psychoneuroendocrinology 99 (2009): 57-65.
  46. Aydemir O and Deveci A. “BDNF measurement in stress-related mood disorders: a review of clinical studies”. Turkish Journal of Psychiatry 20 (2009): 385-391.
  47. Liu T., et al. “A meta-analysis of oxidative stress markers in depression”. PLoS One 10 (2015): e0138904.
  48. Vaidya AD. “Asian medicine-A global blessing. In: Indian Association of Studies in Traditional Asian Medicine (IASTAM) Silver Jubilee Convention Commemorative Volume”. International Journal of PharmTech Research (2005): 821-827.
  49. Mashelkar RA. “India’s R and D: Reaching for the top”. Science 307 (2005): 1415-1417.
  50. Gloth FM., et al. “Vitamin D vs broad spectrum phototherapy in the treatment of seasonal affective disorder”. The Journal of Nutrition, Health and Aging 3 (1999): 5-7.
  51. Walf AA and Frye CA. “A review and update of mechanisms of estrogen in the hippocampus and amygdala for anxiety and depression behavior”. Neuropsychopharmacology 31 (2006): 1097-1111.
  52. Jorge RE., et al. “Influence of major depression on 1 year outcome in patients with traumatic brain injury”. Journal of Neurosurgery 81 (1994): 723-726.
  53. Bynum WF., et al. “Diagnostic and Statistical Manual of Mental Disorders: DSM IV. 4th edition”. Washington, DC: Psychiatric Epidemiology, American Psychiatric Association 4 (1994): 432-436.
  54. López Rubalcava C., et al. “Anxiolytic like actions of the hexane extract from leaves of Annonacherimolia in two anxiety paradigms: Possible involvement of the GABA/benzodiazepine receptor complex”. Life Sciences 78 (2006): 730-737.
  55. Carvalho Freitas MI and Costa M. “Anxiolytic and sedative effects of extracts and essential oil from Citrus aurantium L”. Biological and Pharmaceutical Bulletin 25 (2002): 1629-1633.
  56. Amos S., et al. “Central inhibitory activity of the aqueous extract of Crinum giganteum”. Fitoterapia 74 (2003): 23-28.
  57. Martínez AL., et al. “Neuropharmacological effects of an ethanol extract of the Magnolia dealbata Zucc. leaves in mice”. Journal of Ethnopharmacology 106 (2006): 250-255.
Citation: Mohd Rafi Reshi., et al. “Stress: Its Mechanism, Experimental Assessment and Diagnostic Markers”. EC Clinical and Medical Case Reports 5.8 (2022): 75-88.

PubMed Indexed Article

EC Pharmacology and Toxicology
LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.

PMID: 31143884 [PubMed]

PMCID: PMC6536005

EC Pharmacology and Toxicology
Alzheimer's Pathogenesis, Metal-Mediated Redox Stress, and Potential Nanotheranostics.

PMID: 31565701 [PubMed]

PMCID: PMC6764777

EC Neurology
Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer's Disease and Vascular Dementia: a Retrospective Study.

PMID: 27747317 [PubMed]

PMCID: PMC5065347

EC Pharmacology and Toxicology
Will Blockchain Technology Transform Healthcare and Biomedical Sciences?

PMID: 31460519 [PubMed]

PMCID: PMC6711478

EC Pharmacology and Toxicology
Is it a Prime Time for AI-powered Virtual Drug Screening?

PMID: 30215059 [PubMed]

PMCID: PMC6133253

EC Psychology and Psychiatry
Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse.

PMID: 30417173 [PubMed]

PMCID: PMC6226033

EC Anaesthesia
Arrest Under Anesthesia - What was the Culprit? A Case Report.

PMID: 30264037 [PubMed]

PMCID: PMC6155992

EC Orthopaedics
Distraction Implantation. A New Technique in Total Joint Arthroplasty and Direct Skeletal Attachment.

PMID: 30198026 [PubMed]

PMCID: PMC6124505

EC Pulmonology and Respiratory Medicine
Prevalence and factors associated with self-reported chronic obstructive pulmonary disease among adults aged 40-79: the National Health and Nutrition Examination Survey (NHANES) 2007-2012.

PMID: 30294723 [PubMed]

PMCID: PMC6169793

EC Dental Science
Important Dental Fiber-Reinforced Composite Molding Compound Breakthroughs

PMID: 29285526 [PubMed]

PMCID: PMC5743211

EC Microbiology
Prevalence of Intestinal Parasites Among HIV Infected and HIV Uninfected Patients Treated at the 1o De Maio Health Centre in Maputo, Mozambique

PMID: 29911204 [PubMed]

PMCID: PMC5999047

EC Microbiology
Macrophages and the Viral Dissemination Super Highway

PMID: 26949751 [PubMed]

PMCID: PMC4774560

EC Microbiology
The Microbiome, Antibiotics, and Health of the Pediatric Population.

PMID: 27390782 [PubMed]

PMCID: PMC4933318

EC Microbiology
Reactive Oxygen Species in HIV Infection

PMID: 28580453 [PubMed]

PMCID: PMC5450819

EC Microbiology
A Review of the CD4 T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population

PMID: 26280024 [PubMed]

PMCID: PMC4533840

EC Neurology
Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

PMID: 28066845 [PubMed]

PMCID: PMC5214344

EC Pharmacology and Toxicology
Paradigm Shift is the Normal State of Pharmacology

PMID: 28936490 [PubMed]

PMCID: PMC5604476

EC Neurology
Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia

PMID: 28713879 [PubMed]

PMCID: PMC5510658

EC Neurology
Unilateral Frontosphenoid Craniosynostosis: Case Report and a Review of the Literature

PMID: 28133641 [PubMed]

PMCID: PMC5267489

EC Ophthalmology
OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling

PMID: 29333536 [PubMed]

PMCID: PMC5766278

EC Neurology
Longer Duration of Downslope Treadmill Walking Induces Depression of H-Reflexes Measured during Standing and Walking.

PMID: 31032493 [PubMed]

PMCID: PMC6483108

EC Microbiology
Onchocerciasis in Mozambique: An Unknown Condition for Health Professionals.

PMID: 30957099 [PubMed]

PMCID: PMC6448571

EC Nutrition
Food Insecurity among Households with and without Podoconiosis in East and West Gojjam, Ethiopia.

PMID: 30101228 [PubMed]

PMCID: PMC6086333

EC Ophthalmology
REVIEW. +2 to +3 D. Reading Glasses to Prevent Myopia.

PMID: 31080964 [PubMed]

PMCID: PMC6508883

EC Gynaecology
Biomechanical Mapping of the Female Pelvic Floor: Uterine Prolapse Versus Normal Conditions.

PMID: 31093608 [PubMed]

PMCID: PMC6513001

EC Dental Science
Fiber-Reinforced Composites: A Breakthrough in Practical Clinical Applications with Advanced Wear Resistance for Dental Materials.

PMID: 31552397 [PubMed]

PMCID: PMC6758937

EC Microbiology
Neurocysticercosis in Child Bearing Women: An Overlooked Condition in Mozambique and a Potentially Missed Diagnosis in Women Presenting with Eclampsia.

PMID: 31681909 [PubMed]

PMCID: PMC6824723

EC Microbiology
Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique.

PMID: 31681910 [PubMed]

PMCID: PMC6824726

EC Neurology
Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases.

PMID: 31528859 [PubMed]

PMCID: PMC6746603

EC Psychology and Psychiatry
Can Chronic Consumption of Caffeine by Increasing D2/D3 Receptors Offer Benefit to Carriers of the DRD2 A1 Allele in Cocaine Abuse?

PMID: 31276119 [PubMed]

PMCID: PMC6604646

EC Anaesthesia
Real Time Locating Systems and sustainability of Perioperative Efficiency of Anesthesiologists.

PMID: 31406965 [PubMed]

PMCID: PMC6690616

EC Pharmacology and Toxicology
A Pilot STEM Curriculum Designed to Teach High School Students Concepts in Biochemical Engineering and Pharmacology.

PMID: 31517314 [PubMed]

PMCID: PMC6741290

EC Pharmacology and Toxicology
Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

PMID: 31633124 [PubMed]

PMCID: PMC6800226

EC Neurology
Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

PMID: 29662969 [PubMed]

PMCID: PMC5898812

EC Pharmacology and Toxicology
Hyperbaric Oxygen Therapy for Alzheimer's Disease.

PMID: 30215058 [PubMed]

PMCID: PMC6133268

News and Events

March Issue Release

We always feel pleasure to share our updates with you all. Here, notifying you that we have successfully released the March issue of respective journals and the latest articles can be viewed on the current issue pages.

Submission Deadline for Upcoming Issue

ECronicon delightfully welcomes all the authors around the globe for effective collaboration with an article submission for the upcoming issue of respective journals. Submissions are accepted on/before April 14, 2023.

Certificate of Publication

ECronicon honors with a "Publication Certificate" to the corresponding author by including the names of co-authors as a token of appreciation for publishing the work with our respective journals.

Best Article of the Issue

Editors of respective journals will always be very much interested in electing one Best Article after each issue release. The authors of the selected article will be honored with a "Best Article of the Issue" certificate.

Certifying for Review

ECronicon certifies the Editors for their first review done towards the assigned article of the respective journals.

Latest Articles

The latest articles will be updated immediately on the articles in press page of the respective journals.