Histological changes and APP expression in newborn mice after tramadol.
Journal name: World Journal of Pharmaceutical Research
Original article title: The evaluation of histological changes and imunohistochemical expression of amyloid precursor protein in cerebral and cerebellar cortices in newborn mice after prenatal exposure to tramadol
The WJPR includes peer-reviewed publications such as scientific research papers, reports, review articles, company news, thesis reports and case studies in areas of Biology, Pharmaceutical industries and Chemical technology while incorporating ancient fields of knowledge such combining Ayurveda with scientific data.
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Thair M. Farhan, Huda R. Kammona and Haider J. Mubarak
World Journal of Pharmaceutical Research:
(An ISO 9001:2015 Certified International Journal)
Full text available for: The evaluation of histological changes and imunohistochemical expression of amyloid precursor protein in cerebral and cerebellar cortices in newborn mice after prenatal exposure to tramadol
Source type: An International Peer Reviewed Journal for Pharmaceutical and Medical and Scientific Research
Doi: 10.20959/wjpr201714-9942
Download the PDF file of the original publication
Summary of article contents:
Introduction
Tramadol is a central analgesic extensively used for managing moderate to severe pain, though its use during pregnancy is generally discouraged due to the potential detrimental effects on fetal development. This study focuses on the impact of prenatal exposure to tramadol on the histological features of the cerebral and cerebellar cortices and the expression of amyloid precursor protein (APP) in newborn mice. Through an analysis of various tramadol doses administered to pregnant mice, the authors explore the resultant histological alterations and APP expression linked with the central nervous system (CNS) development of the offspring.
Histological Changes Induced by Tramadol
The study reveals significant histological changes in the cerebral and cerebellar cortices of newborn mice following prenatal tramadol exposure. Notably, tramadol treatment led to cerebral atrophy characterized by a marked reduction in cortical thickness and widening of the subarachnoid space, along with loss of the typical pattern of gyri and sulci. Similarly, cerebellar atrophy was observed, with the absence of Purkinji cells and alterations in the granular layer. These findings indicate that tramadol exposure during pregnancy can lead to profound structural injuries in the developing brain, raising concerns about its safety during pregnancy.
Amyloid Precursor Protein Expression and Its Implications
Amyloid precursor protein (APP), essential for neuronal survival and growth, exhibited significant expression changes in response to tramadol exposure. The study found that APP expression increased with higher doses of tramadol, indicating a potential compensatory mechanism in response to neural damage. This suggests that APP may serve a protective role in the developing cerebral and cerebellar cortices, attempting to mitigate tramadol's harmful effects. The increase in APP expression could be signifying a neuronal response to stress and injury, aligning with its known neuroprotective properties under conditions of cellular insult.
Apoptotic Changes and Vascular Effects
The research also highlights apoptotic changes resulting from tramadol exposure. The histological examination revealed signs of apoptosis within the cerebral cortex, such as nuclear fragmentation, cytoplasmic vacuolation, and pyknosis. Vascular anomalies, including dilatation and rupture of blood vessels accompanied by hemorrhagic areas in the cortex, were evident. These changes suggest that prenatal tramadol exposure may lead to not only direct neuronal damage but also impairments in vascular integrity, which can further exacerbate CNS injury. The interaction between drug exposure and vascular changes presents a multifaceted challenge for fetal brain development.
Conclusion
The findings of this study underscore the significant risks associated with tramadol use during pregnancy, particularly concerning its effects on the cerebral and cerebellar development of newborns. The observed alterations in histology, profound changes in APP expression, and evidence of apoptosis and vascular damage indicate that prenatal tramadol exposure can have serious implications for the developing central nervous system. These results advocate for heightened caution and increased awareness of the potential neurotoxic effects of tramadol when used by pregnant individuals, emphasizing the need for further research in this area to ensure the safety of maternal and fetal health.
FAQ section (important questions/answers):
What was the aim of the study on tramadol exposure?
The study aimed to evaluate the effects of perinatal tramadol treatment on histological features and amyloid precursor protein (APP) expression in the cerebral and cerebellar cortices of newborn mice.
What significant histological changes were observed in the study?
Histological changes included cerebral and cerebellar atrophy, vascular changes, apoptotic alterations, and loss of specific neuronal cell layers in the cerebral and cerebellar cortices after tramadol exposure.
How did tramadol dosage affect APP expression?
The study found that APP expression significantly increased with tramadol dosage, indicating a protective response against neural tissue injury and triggering apoptotic processes.
What methodologies were utilized to assess neuronal changes?
Histological examinations were conducted using H&E staining, while immunohistochemical staining for APP was analyzed using Aperio software for quantitative assessment.
What conclusion can be drawn about tramadol's effects on development?
Tramadol use during pregnancy may lead to detrimental effects on cerebral and cerebellar development, especially at higher doses, as indicated by significant pathological alterations.
What role does amyloid precursor protein (APP) play in the brain?
APP is involved in neuronal survival, synapse formation, and growth, suggesting it may have protective roles in response to cellular insult during neural development.
Glossary definitions and references:
Scientific and Ayurvedic Glossary list for “Histological changes and APP expression in newborn mice after tramadol.”. This list explains important keywords that occur in this article and links it to the glossary for a better understanding of that concept in the context of Ayurveda and other topics.
1) Study (Studying):
The term 'Study' refers to the systematic investigation undertaken to understand the effects of tramadol on the cerebral and cerebellar cortices of newborn mice. This research sheds light on the potential neurotoxic effects of tramadol due to its use during pregnancy, contributing to the scientific body of knowledge around drug safety in prenatal care.
2) Table:
In this context, 'Table' refers to the data presentations that summarize statistics regarding amyloid precursor protein (APP) expression across various experimental groups. These tables facilitate easy comparison of APP levels among the control and treatment groups, helping clarify the results and support conclusions drawn from the study's experiments.
3) Drug:
The term 'Drug' specifically highlights tramadol, an opioid analgesic evaluated in the study. Its pharmacological properties, potential effects on fetal development, and implications during pregnancy are central to understanding the study's aims and findings, particularly regarding its neurotoxic risks and impact on histological features in newborn mice.
4) Arrow:
The term 'Arrow' commonly denotes direction in research studies related to anatomical or histological changes. In this research, arrows likely indicate specific observations in the depicted slides, such as injury sites or pathological changes in mouse brain tissues, guiding readers in their understanding of the findings presented visually.
5) Pregnant:
The word 'Pregnant' pertains to the primary subjects of the study—the pregnant mice that were exposed to tramadol. This demographic is crucial as the effects of drug exposure during pregnancy can have lasting implications on the offspring's health, providing insight into maternal-fetal health relationships and clinical pharmacology.
6) Death:
The term 'Death' refers to the observed apoptotic changes resulting from tramadol exposure, indicating cell death in the cerebral and cerebellar cortices. Understanding the mechanisms behind this apoptosis is essential, as it reveals the drug's potential to cause irreversible damage to developing neurons, raising concerns about prenatal drug exposure.
7) Activity:
The term 'Activity' relates to neuronal activity and responses to tramadol stimulation. In the context of the study, it could refer to the behavioral or physiological responses observed in newborn mice after drug exposure, highlighting how pharmacological agents like tramadol can alter normal brain function and development.
8) Disease:
In this context, 'Disease' relates to the potential pathological conditions resulting from tramadol exposure during pregnancy. The study's findings might contribute to understanding neurodevelopmental disorders or cognitive deficits that could arise due to prenatal opioid exposure, emphasizing the relevance of the research to public health and medicine.
9) Animal:
The term 'Animal' signifies the use of animal models, specifically pregnant mice, in the study. This choice is pivotal for conducting ethical and controlled experiments that provide preliminary data on drug effects before clinical testing in humans, bridging laboratory research to potential therapeutic implications.
10) Blood:
The term 'Blood' connects with the vascular changes observed in the study, such as hemorrhagic areas in the cerebral cortex. Assessing the impact of tramadol on blood supply to brain tissues is essential for understanding its overall effects on cerebral development and potential risks of vascular dysfunction.
11) Pain:
The term 'Pain' underscores the central action of tramadol as an analgesic. The study examines the broader implications of pain management in pregnant populations and highlights how analgesics can potentially impact fetal development, emphasizing the need for caution when prescribing medications during pregnancy.
12) Transmission:
The term 'Transmission' relates to the processes of neuronal communication affected by the drug. The study implicates changes in synaptic transmission due to altered APP expression, which can influence cognitive functions and neural plasticity in the offspring exposed to tramadol in utero.
13) Medicine:
The term 'Medicine' encompasses the broader field within which the study sits, including pharmacology, toxicology, and maternal-fetal medicine. The research contributes significantly to understanding how medications like tramadol can have adverse effects on fetal development, informing medical guidance for pregnant individuals.
14) Surface:
The term 'Surface' likely refers to the anatomical features of the brain, such as the cerebral surface morphology observed in the study. Changes in surface characteristics like sulci and gyri are important histological markers indicating developmental alterations resulting from tramadol exposure.
15) Water:
The term 'Water' is indicative of the medium (deionized water) used for diluting tramadol for injection in the study. The purity and quality of the solvent can influence experimental outcomes and highlight the importance of proper formulation in pharmacological research.
16) Pharmacological:
The term 'Pharmacological' pertains to the study's focus on the effects of tramadol as a therapeutic agent. It emphasizes the investigation into how this drug's properties can influence biological systems, particularly in a developing organism, revealing the dual characteristics of therapeutic benefit and potential harm.
17) Pharmacology:
The term 'Pharmacology' is the broader discipline that encompasses the study of drug actions and effects. This research falls under pharmacology, specifically in understanding tramadol's impact on fetal development and its safety during pregnancy, crucial for responsible drug application in healthcare.
18) Discussion:
The term 'Discussion' signifies the section within scientific literature where the implications of findings are interpreted. This part of the research comprehensively analyzes results concerning the effects of tramadol on fetal brain development, emphasizing the need for caution and further research in clinical settings.
19) Developing:
The term 'Developing' highlights the focus on an important stage, namely the developing brains of newborn mice. This aspect is critical as it relates to how prenatal exposures can influence growth, structure, and function, establishing a link between drug exposure and neurodevelopmental outcomes.
20) Science (Scientific):
The term 'Science' encapsulates the entire endeavor of exploring drug impacts on biological systems through empirical methods. This research contributes to the overarching scientific knowledge on teratology and pharmacology, aiding in public health decisions and the responsible use of medication during pregnancy.
21) Toxicity:
The term 'Toxicity' relates to the potential harmful effects tramadol may have on pregnant individuals and their offspring. Assessing toxicity is essential for determining safe therapeutic ranges and addressing concerns regarding long-term developmental impacts of medications taken during pregnancy.
22) Mutation:
The term 'Mutation' supports discussions in the study regarding genetic anomalies that could arise from environmental factors, such as drug exposure during pregnancy. While the study doesn't explicitly explore genetic mutations, it implies potential long-term changes resulting from disturbances in normal development due to tramadol.
23) Species:
The term 'Species' signifies the specific biological context of the study: mice as model organisms. Research conducted on specific species allows scientists to extrapolate potential effects in humans indirectly and better understand biological processes common to vertebrates, particularly during critical periods of development.
24) Edema (Oedema):
The term 'Oedema' relates to the observation of fluid accumulation in tissues as a result of tramadol exposure. It indicates pathological changes in the brain, such as vascular alterations, highlighting potential mechanisms through which drugs cause changes in cerebral structures during development.
25) Nature:
The term 'Nature' refers to the inherent qualities of drugs and their biological effects. In the context of this study, it emphasizes understanding tramadol's natural mechanisms of action and its physiological repercussions on neurodevelopment, implicating much broader concerns regarding drug safety and infant health.
26) Shalem (Salem):
The term 'Salem' likely refers to a specific author's contribution to this research or the research institution's reference. As part of the authorship of the study, their name carries weight in establishing credibility, highlighting individual contributions in advancing knowledge regarding drug effects in biomedical research.
27) Kohli:
The term 'Kohli' signifies another author involved in the study. The inclusion of multiple authors reflects the collaborative essence of scientific research and the expertise required to explore complex interactions in pharmacology and developmental biology thoroughly.
28) Chang:
The term 'Chang' underlines the presence of another contributing researcher, indicating collaboration in the study. The contributions of various researchers help ensure comprehensive coverage of the study subject and enhance the quality and validity of the research findings.
29) Beta:
The term 'Beta' is potentially associated with beta-secretase, an enzyme involved in amyloid precursor protein processing. This link is significant in understanding the pathways that influence neuronal health and degeneration, particularly in the context of neurodegenerative diseases such as Alzheimer's.
30) Post:
The term 'Post' suggests an approach regarding post-exposure effects observed in subjects. It illustrates the timeline of observing outcomes and highlights the significance of monitoring long-lasting effects after prenatal drug exposure in developmental studies.
31) Ter:
The term 'Ther' is short for therapy, relating to the therapeutic actions of tramadol. Understanding its therapeutic profile helps elucidate the balance between managing pain in pregnant individuals and ensuring the safety of fetal development.
32) Male:
The term 'Male' references the gender of the animal subjects used in the study. Although the study focuses on pregnant females, recognizing the gender of the subjects may provide essential insights into the physiological and developmental differences that could influence study outcomes.