scholarly journals CNS Safety Screening Under ICH S7A Guidelines Requires Observations of Multiple Behavioral Units to Assess Motor Function

2019 ◽  
Vol 38 (5) ◽  
pp. 339-356 ◽  
Author(s):  
David V. Gauvin ◽  
Zachary J. Zimmermann ◽  
Jill A. Dalton ◽  
Theodore J. Baird ◽  
Mary-Jeanne Kallman
Keyword(s):  
Nervous System ◽  
Muscle Tone ◽  
Neural Pathways ◽  
Experimental Analysis Of Behavior ◽  
Safety Testing ◽  
3 Dimensional ◽  
Technical Requirements ◽  
Good Laboratory ◽  
Home Cage Activity ◽  
Tier I

In the adoption of behavior as a critical end point in safety pharmacology and neurotoxicity screening, federal regulatory agencies have shifted the predominating scientific perspective from pharmacology back to the experimental analysis of behavior (psychology). Nowhere is this more evident than in tier I safety assessment of the central nervous system (CNS). The CNS and peripheral nervous system have multiple behavioral units of general activity. A complete picture of the motor control neural pathways cannot be measured by any one single approach. The CNS safety protocols under International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use S7A are required to be conducted in accordance with Good Laboratory Practices by trained technical staff. The CNS safety assessments necessitate the inclusion of a thorough and detailed behavioral analysis of home cage activity, the response to handling, and transportation to and observations within an open-field apparatus with ancillary measures of basal muscle tone, muscle strength, and tremor in a functional observation battery, as well as quantitative measurements of 3-dimensional activity in an automated photobeam arena. Cost-cutting initiatives or a radical application of the “reduce use” principle of the 3 Rs only jeopardize the spirit, intent, and predictive validity of tier I safety testing assays dictated by current drug safety guidelines.

Serial thin sectioning for pre- and post-embedding immunohistochemistry: Achieving consistent and reliable results for a 3-D reconstruction

1993 ◽  
Vol 51 ◽  
pp. 328-329
Author(s):  
Antonia M. Milroy
Keyword(s):  
Nervous System ◽  
Computer Assisted ◽  
Serial Sectioning ◽  
Electron Microscopic ◽  
High Quality ◽  
New Techniques ◽  
3 Dimensional ◽  
Multiple User ◽  
Thin Sectioning ◽  
Subcellular Level

In recent years many new techniques and instruments for 3-Dimensional visualization of electron microscopic images have become available. Higher accelerating voltage through thicker sections, photographed at a tilt for stereo viewing, or the use of confocal microscopy, help to analyze biological material without the necessity of serial sectioning. However, when determining the presence of neurotransmitter receptors or biochemical substances present within the nervous system, the need for good serial sectioning (Fig. 1+2) remains. The advent of computer assisted reconstruction and the possibility of feeding information from the specimen viewing chamber directly into a computer via a camera mounted on the electron microscope column, facilitates serial analysis. Detailed information observed at the subcellular level is more precise and extensive and the complexities of interactions within the nervous system can be further elucidated.We emphasize that serial ultra thin sectioning can be performed routinely and consistently in multiple user electron microscopy laboratories. Initial tissue fixation and embedding must be of high quality.

Advances in bioelectronic medicine: noninvasive electrical, ultrasound and magnetic nerve stimulation

2019 ◽  
Vol 2 (4) ◽  
pp. 143-150
Author(s):  
Jason R Fritz ◽  
Jared M Huston
Keyword(s):  
Nervous System ◽  
Nerve Stimulation ◽  
Peripheral Nerves ◽  
Therapeutic Potential ◽  
Acute Onset ◽  
Neural Pathways ◽  
Pulse Generators ◽  
Bioelectronic Medicine ◽  
Potential Impact ◽  
Electrical Signaling

The mammalian nervous system has evolved over millions of years to protect the host. Harnessing neural pathways for therapeutic purposes is postulated to enhance treatment specificity and minimize adverse reactions. Bioelectronic medicine aims to diagnose and treat diseases through devices that regulate electrical signaling within the nervous system. Traditionally, this was accomplished via surgical implantation of electrical pulse generators directly onto peripheral nerves. While efficacious, this approach has significant limitations, including complications and associated costs of surgical procedures, and practical issues with treating acute onset and/or short-lived diseases with invasive approaches. Novel stimulation paradigms are currently under development to overcome these clinical challenges and ultimately expand the therapeutic potential of bioelectronic medicine. Here we review noninvasive electrical, ultrasound and magnetic nerve stimulation strategies in the context of more invasive electrical therapies, and discuss their potential impact on the field of bioelectronic medicine.

scholarly journals Noninvasive approach to mend the broken heart: Is “remote conditioning” a promising strategy for application in humans?

2017 ◽  
Vol 95 (10) ◽  
pp. 1204-1212 ◽  
Author(s):  
Táňa Ravingerová ◽  
Veronika Farkašová ◽  
Lucia Griecsová ◽  
Martina Muráriková ◽  
Slavka Carnická ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cost Effective ◽  
Neural Pathways ◽  
Protective Mechanisms ◽  
Clinical Role ◽  
Technical Requirements ◽  
Promising Strategy ◽  
Remote Organ ◽  
Local Stimulus

Currently, there are no satisfactory interventions to protect the heart against the detrimental effects of ischemia–reperfusion injury. Although ischemic preconditioning (PC) is the most powerful form of intrinsic cardioprotection, its application in humans is limited to planned interventions, due to its short duration and technical requirements. However, many organs/tissues are capable of producing “remote” PC (RPC) when subjected to brief bouts of ischemia–reperfusion. RPC was first described in the heart where brief ischemia in one territory led to protection in other area. Later on, RPC started to be used in patients with acute myocardial infarction, albeit with ambiguous results. It is hypothesized that the connection between the signal triggered in remote organ and protection induced in the heart can be mediated by humoral and neural pathways, as well as via systemic response to short sublethal ischemia. However, although RPC has a potentially important clinical role, our understanding of the mechanistic pathways linking the local stimulus to the remote organ remains incomplete. Nevertheless, RPC appears as a cost-effective and easily performed intervention. Elucidation of protective mechanisms activated in the remote organ may have therapeutic and diagnostic implications in the management of myocardial ischemia and lead to development of pharmacological RPC mimetics.

Differential Innervation of Tissues Located at Traditional Acupuncture Points in the Rat Forehead and Face

2018 ◽  
Vol 36 (6) ◽  
pp. 408-414 ◽  
Author(s):  
Jia Wang ◽  
Jingjing Cui ◽  
Chen She ◽  
Dongsheng Xu ◽  
Zhiyun Zhang ◽  
...  
Keyword(s):  
Nervous System ◽  
Sensory Neurons ◽  
Motor Neurons ◽  
Acupuncture Point ◽  
Acupuncture Points ◽  
Motor Nucleus ◽  
Neural Pathways ◽  
Trigeminal Motor Nucleus ◽  
Facial Motor Nucleus ◽  
Neural Tracing

Objectives To compare the neural pathways associated with the tissues located at different traditional acupuncture points in the rat forehead and face using the cholera toxin B subunit (CTB) neural tracing technique. Methods After injection of CTB into the tissues at GB14, ST2 and ST6 in the rat, the neural labelling associated with each acupuncture point was revealed by fluorescent immunohistochemistry of the nervous system, including the trigeminal ganglion (TRG), cervical dorsal root ganglia (DRG), spinal cord and brain. Results The CTB labelling included sensory neurons and their transganglionic axonal terminals, as well as motor neurons. The labelled sensory neurons associated with GB14, ST2 and ST6 were distributed in both the TRG and cervical DRG, and their centrally projected axons terminated in an orderly fashion at their corresponding targets in the spinal trigeminal nucleus and cervical spinal dorsal horn. In addition, labelled motor neurons were observed in the facial motor nucleus, trigeminal motor nucleus and cervical spinal ventral horn, in which facial motor neurons projected to the tissues located at all three acupuncture points. Trigeminal motor neurons innervated both ST2 and ST6, while spinal motor neurons only correlated with ST6. Conclusions These results indicate that the tissues located at each of these three traditional acupuncture points in the rat forehead and face has its own sensory and motor connection with the nervous system in a region-specific pattern through distinct neural pathways. Understanding the neuroanatomical characteristics of acupuncture points from the peripheral nervous system to the central nervous system should help inform acupuncture point selection according to the demands of the clinical situation.

Collaborative Study on 3-Dimensional Sonography for the Prenatal Diagnosis of Central Nervous System Defects

2011 ◽  
Vol 30 (7) ◽  
pp. 1003-1008 ◽  
Author(s):  
Giuseppe Rizzo ◽  
Alfred Z. Abuhamad ◽  
Beryl R. Benacerraf ◽  
Rabih Chaoui ◽  
Edgardo Corral ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Prenatal Diagnosis ◽  
Collaborative Study ◽  
3 Dimensional ◽  
Central Nervous System Defects

Resection of a cystic brainstem hemangioblastoma via a retrosigmoid approach

2014 ◽  
Vol 36 (v1supplement) ◽  
pp. 1 ◽  
Author(s):  
Brian Lee ◽  
Yvette D. Marquez ◽  
Steven L. Giannotta
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurological Dysfunction ◽  
Neural Pathways ◽  
Technical Challenge ◽  
Cystic Component ◽  
Complete Surgical Resection ◽  
Close Proximity ◽  
The Central Nervous System ◽  
Vascular Structures

Lesions of the brainstem pose a technical challenge due to their close proximity to critical vascular structures, neural pathways, and nuclei. Hemangioblastomas are rare lesions of the central nervous system and can cause significant neurological dysfunction, primarily due to enlargement of the cystic component. This is especially relevant when hemangioblastomas occur in eloquent brainstem regions. However, the outcomes after hemangioblastoma resection are good if complete surgical resection of the tumor of the mural nodule, can be achieved. This video demonstrates the excision of a brainstem hemangioblastoma via a left retrosigmoid craniotomy under Stealth guidance.The video can be found here: http://youtu.be/bCkuaPwMV20.

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