Hidden Injury to Key Spinal interneurons in Bipolar Illness?

from an email written to a researcher about my thoughts on this subject:

Here are some references to current papers that I found on  sleep deprivation and effects on the motor act of breathing…..[which involves communication between the neurons of the brainstem and the neurons and neuronal  fibres of the spinal cord, something which I think we too often overlook].

There is “new” evidence that sleep deprivation can disturb “control of breathing and even precipitate [hidden] respiratory  failure,due to [reversible] messing with connections between the brain and the respiratory muscles, including the spine and its neurons.    [I am not a scientist or doctor so…].

As I mentioned, my friend Paula has abnormal daytime control of breathing [as shown by her baseline depressed respiratory rate and changed respiratory reflexes] so sleep deprivation, in her case, would not be good.

Please see:

Impact of Sleep Deprivation on Respiratory Motor Output and Endurance. A Physiological Study

Am J Respir Crit Care Med . 2020 Apr 15;201(8):976-983. doi: 10.1164/rccm.201904-0819OC.

Christophe Rault 1 2Aude Sangaré 3Véronique Diaz 1 2Stéphanie Ragot 1 4Jean-Pierre Frat 1 5Mathieu Raux 6 7Thomas Similowski 6 8René Robert 1 5Arnaud W Thille 1 5Xavier Drouot 1 2 3 9 

” One night of sleep deprivation reduces respiratory motor output by altering its cortical component with subsequent reduction of inspiratory endurance by half. 

[These results suggest that altered sleep triggers severe brain dysfunctions that could precipitate respiratory failure.”] 

AND

Clarifying the Effect of Sleep Deprivation on the Respiratory Muscles

Franco Laghi12Hameeda Shaikh12

  • PMID: 31951467

Free PMC article

“The elegant investigation of Rault and colleagues (1) is provocative. The investigators have set the stage for the objective study of the physiologic maze that accompanies sleep deprivation. One challenge will be to unravel the sex-specific effect of sleep deprivation on dyspnea, spinal and supraspinal reflex inhibition, and function of the primary motor cortex. Another challenge will be to determine the effect of sleep deprivation in critically ill patients, including those who fail invasive and noninvasive ventilation. The challenge is formidable, but now is the time to tackle it.”

This is truly new and truly fascinating, I think.

I think that the time has come to study the skeletal neural motor control of breathing  involving the spine’s ability to respond to commands of the primary motor cortex. [separate from the lungs].

I also think that exchange of external gases, plus  the ability to deal with accumulating internal metabolic gases, and stability of respiratory pH,  require intact neurons in the primary motor cortex and intact neurons and neural fibres in the cervical spine.

Measuring baseline respiratory rate in ambulatory patients is an easy way to detect localized motor damage to the neurons of the cervical spinal cord [or their fibres] in ambulatory patients.[a sign of hidden past spinal injury -at birth or after accident or severe illness-  and spontaneous recovery].

The role of the spine is  an overlooked part of “control of breathing” and the motor ability to breathe.   Accumulation of internal and external gases [hypercapnia] can lead to a range of mental neurotoxic symptoms, which we all recognize when we are intoxicated with depressants or stimulants. Sublethal signs of poisoning [lead, mercury, etc..] also cause neurotoxic effects disturbing everyday function. … All chemicals affect the motor pattern of breathing in different ways .

 I think that there is an important connection linking motor skeletal patterns. of breathing to mental status and gas exchange. . Abnormal motor skeletal patterns of breathing can easily lead to different levels of  abnormal mental status [due to buildup of internal gases -eg. PaC02 for one] .

My friend Paula has no eupneic breathing at rest. 

Her respiratory rate at rest is never 12 to 20 breaths per minute.  

Her baseline respiratory rate is 3 breaths per minute with continual help of the abdominal muscles [acting like an extra pump [to squeeze out air when exhaling…with every exhale].  This works most of the time but this is not a normal way to breathe. She is not aware that her breathing is abnormal.  Vital signs such as breathing and blood pressure are unconscious, co-ordinated by the involuntary or autonomic nervous system.

I think that during Paula’s difficult adjustment to room air at birth  [or lack of adjustment – since she needed resuscitation and transfusion], some of the spinal neurons needed for normal breathing might have been eliminated [due to the period of hypoxia she endured at the moment of birth]. and when she subsequently survived,  other dormant neural pathways were activated to allow her to breathe, but in a different way…in other words, considerable remodeling of the motor neural/skeletal respiratory network  had to occur to allow her to breathe.…[ and I think that even in normal birth, some remodelling occurs in all of us, in order for the respiratory neurons and networks to adjust to whatever type of outside air is present at birth,; the ventilatory system is necessarily dynamic and the baseline is “set” in this way, being a little bit different in all of us].

I am trying to reverse engineer how Paula came to breathe the way she does…..It is a useful intellectual device and there is research to support the idea of remodelling of the spinal neural breathing network after injury and/or illness..

It has led me to look at research papers  on the neural circuits of the spinal cord more carefully.

See

Exp Neurol. 2020 Jun; 328: 113256. 

Published online 2020 Feb 19. doi: 10.1016/j.expneurol.2020.113256

Targeted activation of spinal respiratory neural circuits

Michael D. Sunshine,a,b,c,d Tommy W. Sutor,a,c,d Emily J. Fox,a,d,e and  David D. Fullera,b,d,*

“Behavior of the spinal respiratory circuit

Breathing, and thus the activity of respiratory neurons and networks, changes dynamically with metabolic demand/physical activity, posture, time of day, sleep-wake cycle, etc. In addition, the respiratory neural control network is capable of considerable plasticity on both short and longer time scales (Fuller and Mitchell, 2017). It is also well established that spinal interneuron circuits are highly adaptable to prevailing conditions (Jankowska, 2001), and in regards to spinal respiratory networks both injury and disease can lead to considerable remodeling (Zholudeva et al., 2017). Thus, we suggest that it is difficult to draw firm conclusions regarding spinal interneuron function based on the discharge patterns recorded during a particular experimental condition (Jankowska, 2001). Rather, conclusions need to be restricted to the particular condition, with the understanding that the physiologic role of the particular cell or propriospinal network may be different if circumstances are changed.”

And 

  To my mind, measuring respiratory rate, depth and pattern, is a way to measure the neural function of the spinal cord.  This is why measuring respiratory rate [as a first step] is very important to finding evidence of past lesions of spinal respiratory neurons in the cord, especially in ambulatory patients with altered mental status and possible neurotoxic signs of difficulties with internal gas exchange not linked to the lungs.

Front Syst Neurosci. 2019; 13: 84. 

10.3389/fnsys.2019.00084

Role of Propriospinal Neurons in Control of Respiratory Muscles and Recovery of Breathing Following Injury

Victoria N. Jensen,1 Warren J. Alilain,2,3 and Steven A. Crone4,5,6,*

There is convincing evidence that propriospinal neurons help pattern the activity of respiratory muscles in order to meet the needs of the organism. This is a dynamic process that involves a variety of neurons with unique roles. In SCI, the need to modulate motor function is escalated and the roles of propriospinal neurons in the control of breathing may be amplified. Indeed, there is mounting evidence that spinal circuitry is altered after disease and injury, that spinal network plasticity contributes to recovery, and that propriospinal neurons are an attractive therapeutic target to improve respiratory motor function. Developmental markers that can be used to identify and genetically mark (or manipulate) specific classes of propriospinal neurons have been valuable tools to investigate the function of neurons within circuits. These tools will continue to be useful as we investigate mechanisms of neuroplasticity that promote recovery of function following injury. Overall, a better understanding of the circuitry that controls breathing in uninjured animals and the changes that occur following injury should lead to new therapies to improve breathing.

 Abnormal baseline respiratory rates can be a sign of past spinal cord injury and, especially in ambulatory patients, a sign of recovery of the spinal interneurons using latent neural pathways. Signs of internal neurotoxicity due to difficulty with internal gas control [despite normal lungs], can occur when these naturally improvised physiological breathing solutions fail.

I list these common neurotoxic symptoms in the last blogpost.

I love this stuff!!!!  So fascinating!

Please feel free to share this email [or blogpost] with other interested researchers.

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