Regulation of Breathing and Cerebrovascular reactivity

Many patients suffering from neurological, cardiovascular, and metabolic diseases show major alterations in cerebrovascular reactivity. The research paper below unexpectedly found that normal cerebrovascular reactivity is required for the regulation of respiration and emotional behaviour. ….

Cerebral blood flow (CBF) supplies energy substrates to the brain and removes metabolic products. Therefore, CBF is tightly controlled (12). Since the 19th century, it has been known that carbon dioxide (CO2)/H+ is one of the strongest stimuli for increasing brain perfusion (35). While it may seem plausible that as the major product of metabolism CO2 increases CBF to enhance its removal and replenish nutrients, a physiological function of cerebrovascular reactivity to CO2 has never been proven experimentally. Also, the molecular mechanisms underlying cerebrovascular reactivity are still debated. This lack of knowledge is surprising because many patients suffering from neurological, cardiovascular, and metabolic diseases show major alterations in cerebrovascular reactivity. In fact, cerebrovascular reactivity is routinely monitored as a diagnostic marker to detect early stages of vascular pathology (6). In the context of the multifaceted conditions associated with vascular risk factors, it has been difficult to delineate the functional consequences of impaired cerebrovascular reactivity. Therefore, we have investigated the mechanisms underlying CO2-induced perfusion changes in the brain. Based on the obtained knowledge, we were able to selectively interfere with cerebrovascular reactivity and unexpectedly found that its integrity is required for the regulation of respiration and emotional behavior.Impaired endothelium-mediated cerebrovascular reactivity promotes anxiety and respiration disorders in mice.  Jan Wenzel, Cathrin E. Hansen, Carla Bettoni, Miriam A. Vogt, Beate Lembrich, Rentsenkhand Natsagdorj, Gianna Huber, Josefine Brands, Kjestine Schmidt, Julian C. Assmann, Ines Stölting, Kathrin Saar, Jan Sedlacik, Jens Fiehler, Peter Ludewig, Michael Wegmann, Nina Feller, Marius Richter, Helge Müller-Fielitz, Thomas Walther, Gabriele M. König,  Evi Kostenis, Walter Raasch, Norbert Hübner, Peter Gass, Stefan Offermanns, Cor de Wit,  Carsten A. Wagner, and  Markus Schwaninger PNAS January 21, 2020 117 (3) 1753-1761; first published January 2, 2020; https://doi.org/10.1073/pnas.1907467117

Cerebral blood flow is also closely linked to neuronal activity, brain perfusion SPECT can also be used to evaluate and monitor certain neurological disorders and psychiatric disorders, such as dementia, Alzheimer’s diseases, mood disorders, and attention-deficit disorder. It can also be used to assess brain trauma, substance abuse, and chemical exposure. Volume 3 Yong Du, Habib Zaidi, in Encyclopedia of Biomedical Engineering, 2019 Neurology and Psychiatry from https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/brain-perfusion

Is a high CPP harmful? [eg. from hypercapnia ]…..
When brain injury occurs, cerebral capillaries can become “leaky” or more permeable to water.  In addition, cerebral blood vessels may dilate in response to brain tissue injury, hypoxemia, hypercarbia, acidosis or hypotension.  If the BP becomes elevated, the increased CPP can lead to increased cerebral blood flow.  When combined with increased capillary permeability or cerebral vasodilation, blood flow can increase to the point where brain edema worsens.The goal for maintaining the CPP is to ensure that the CPP is high enough to perfuse the brain; while preventing excessive CPP elevations that might worsen any cerebral edema.” Cerebral Pefusion Pressure Critical Care Trauma Centre Brenda Morgan Clinical Educator, CCTC May 12, 2001, Updated: January 15, 2019 https://www.lhsc.on.ca/critical-care-trauma-centre/cerebral-pefusion-pressure

This is too complicated for me. But relevant, I think , to hypercapnia and to raise blood pressure and increased cranial pressure. [and ventilatory rate].

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