Editing Cushing reflex (section)

==Mechanism==
The Cushing reflex is complex and seemingly paradoxical.<ref name= Beiner>{{cite journal | last = Beiner| first = JM|author2=CS Olgiyy |author3=AB DuBois | title = Cerebral blood flow changes in response to elevated intracranial pressure in rabbits and bluefish: a comparative study | journal =  Comparative Biochemistry and Physiology Part A: Physiology| volume = 116| issue = 3| pages = 245–52| doi = 10.1016/s0300-9629(96)00206-x| pmid =9102186 |date=March 1997 | doi-access = free}}</ref> The reflex begins when some event causes increased intracranial pressure (ICP). Since [[cerebrospinal fluid]] is located in an area surrounded by the skull, increased ICP consequently increases the pressure in the fluid itself. The pressure in the cerebral spinal fluid eventually rises to the point that it meets and gradually exceeds the [[mean arterial pressure|mean arterial blood pressure]] (MAP). When the ICP exceeds the MAP, [[arteriole]]s located in the brain's [[cerebrum]] become compressed. Compression then results in diminished blood supply to the brain, a condition known as cerebral [[ischemia]].<ref name=Dickinson>{{cite journal | last = Dickinson| first = CJ| title = Reappraisal of the Cushing reflex: the most powerful neural blood pressure stabilizing system | journal = Clinical Science| volume = 79| issue = 6| pages = 543–50| year = 1990| doi = 10.1042/cs0790543| pmid = 2176941}}</ref>

During the increase in ICP, both the [[sympathetic nervous system]] and the [[parasympathetic nervous system]] are activated. In the first stage of the reflex, sympathetic nervous system stimulation is much greater than parasympathetic stimulation.<ref name=Pasztor/> The sympathetic response activates [[alpha-1 adrenergic receptor]]s, causing constriction of the body's [[Artery|arteries]].<ref name=Woodman>{{cite journal | last = Woodman| first = OL|author2=SF Vatner| title = Coronary vasoconstriction mediated by α1- and α2-adrenoceptors in conscious dogs. | journal = Am. J. Physiol.| volume = 253| issue = 2 Pt 2| pages = H388–93| date = August 1987| doi = 10.1152/ajpheart.1987.253.2.H388| pmid =2887122}}</ref> This constriction raises the total resistance of blood flow, elevating blood pressure to high levels, which is known as [[hypertension]]. The body's induced hypertension is an attempt to restore blood flow to the ischemic brain. The sympathetic stimulation also increases the rate of heart [[contractility|contractions]] and [[cardiac output]].<ref name=Brodal>{{cite book |author= Per Brodal| title= The Central Nervous System: Structure and Function| publisher= Oxford University Press US.| year= 2004| pages=369–396}}</ref>  Increased heart rate is also known as [[tachycardia]]. This combined with hypertension is the first stage of the Cushing reflex.{{cn|date=March 2021}}

Meanwhile, [[baroreceptor]]s in the [[aortic arch]] detect the increase in blood pressure and trigger a parasympathetic response via the [[vagus nerve]]. This induces bradycardia, or slowed heart rate, and signifies the second stage of the reflex.<ref name=Hacket>{{cite journal | last = Hackett| first = J.G.|author2=F. M. Abboud |author3=A. L. Mark |author4=P. G. Schmid |author5=D. D. Heistad| title = Coronary vascular responses to stimulation of chemoreceptors and baroreceptors.| journal = Circ. Res.| volume = 31| issue = 1| pages = 8–17| doi = 10.1161/01.res.31.1.8| pmid =4402639 |date=July 1972 | doi-access = free}}</ref> Bradycardia may also be caused by increased ICP due to direct mechanical distortion of the vagus nerve and subsequent parasympathetic response.{{citation needed|date=June 2011}} Furthermore, this reflexive increase in parasympathetic activity is thought to contribute to the formation of [[Cushing ulcer]]s in the stomach, due to uncontrolled activation of the [[parietal cell]]s. The blood pressure can be expected to remain higher than the pressure of the raised cerebral spinal fluid to continue to allow blood to flow to the brain. The pressure rises to the point where it overcomes the resisting pressure of the compressed artery, and blood is allowed through, providing oxygen to the hypoxic area of the brain. If the increase in blood pressure is not sufficient to compensate for the compression on the artery, [[infarction]] occurs.<ref>{{cite book |last1=Guyton |first1=Arthur |last2=Hall |first2=John |editor1-first=Rebecca |editor1-last=Gruliow |title=Textbook of Medical Physiology |type=Book |edition=11th |year=2006 |publisher=Elsevier Inc. |location=Philadelphia, Pennsylvania |isbn=978-0-7216-0240-0 |page=213  |chapter=Chapter 18: Nervous Regulation of Circulation, and a Rapid Control of Arterial Pressure}}</ref>

Raised ICP, tachycardia, or some other endogenous stimulus can result in distortion and/or increased pressure on the [[brainstem]]. Since the brainstem controls involuntary breathing, changes in its homeostasis often results in irregular respiratory pattern and/or [[apnea]].<ref name=Barash>{{cite book |author1=P Barash |author2=B Cullen |author3=R Storlting | title= Clinical Anesthesia|url=https://archive.org/details/clinicalanesthes00bara |url-access=registration | publisher= JB Lippincott| location= Philadelphia| year= 1992| pages=[https://archive.org/details/clinicalanesthes00bara/page/520 520]|isbn=9780397511600 }}</ref>  This is the third and final stage of the reflex.

The role of the [[central chemoreceptors]] in the Cushing reflex is unclear. In most normal pressure responses the chemoreceptors and baroreceptors work together to increase or decrease blood pressure. In the Cushing reflex, the central chemoreceptors are likely involved in the detection of ischemia, contributing to the sympathetic surge and hypertension in the first phase of the reflex, and work in opposition to the baroreceptors, contributing to the combined high sympathetic and parasympathetic activation.<ref>{{Citation|last=Hall|first=John|title=Nervous Regulation of the Circulation and Rapid Control of Arterial Pressure|date=2012|url=https://www.clinicalkey.com/#!/content/book/3-s2.0-B9781455770052000184?scrollTo=%23hl0000379|work=Guyton and Hall Textbook of Medical Physiology|pages=215–255|publisher=Elsevier|isbn=9781455770052|access-date=2019-11-10}}</ref>

===Function===

Raised intracranial pressure can ultimately result in the shifting or crushing of [[brain tissue]], which is detrimental to the physiological well-being of patients. As a result, the Cushing reflex is a last-ditch effort by the body to maintain [[homeostasis]] in the [[brain]]. It is widely accepted that the Cushing reflex acts as a [[baroreflex]], or homeostatic mechanism for the maintenance of blood pressure, in the cranial region.<ref name=Wan /> Specifically, the reflex mechanism can maintain normal cerebral blood flow and pressure under stressful situations such as ischemia or subarachnoid hemorrhages. A case report of a patient who underwent a spontaneous subarachnoid hemorrhage demonstrated that the Cushing reflex played a part in maintaining cerebral perfusion pressure (CPP) and cerebral blood flow.<ref name=Wan>{{cite journal | last = Wan| first = WH|author2=BT Ang |author3=E Wang | title = The cushing response: A case for a review of its role as a physiological reflex.| journal = J Clin Neurosci| volume = 15| issue = 3| pages = 223–8| date = Jan 7, 2008| doi = 10.1016/j.jocn.2007.05.025| pmid = 18182296| s2cid = 43225467}}</ref> Eventually, the ICP drops to a level range where a state of induced hypertension in the form of the Cushing reflex is no longer required. The Cushing reflex was then aborted, and CPP was maintained. It has also been shown that an increase in mean arterial pressure due to hypertension, characteristic of the reflex, can cause the normalization of CPP.<ref name=Dickinson /> This effect is protective, especially during increased intracranial pressure, which creates a drop in CPP.<ref>{{Cite journal |last1=Wittenberg |first1=Philippa |last2=McBryde |first2=Fiona D. |last3=Korsak |first3=Alla |last4=Rodrigues |first4=Karla L. |last5=Paton |first5=Julian F. R. |last6=Marina |first6=Nephtali |date=March 6, 2025 |title=On the regulation of arterial blood pressure by an intracranial baroreceptor mechanism |journal=The Journal of Physiology |doi=10.1113/JP285082 |pmid=39924875 |url=https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP285082|doi-access=free |pmc=7617620 }}</ref>

=== Cushing's triad {{anchor|Cushing's_Triad}} ===
'''Cushing's triad''' refers to when all of these symptoms are seen together:<ref>{{Cite book |last=Blumenfeld |first=Hal |title=Neuroanatomy through clinical cases |publisher=Sinauer Associates |year=2022 |isbn=978-1-60535-962-5 |edition=3rd |location=Sunderland, MA, USA |pages=143 |language=en}}</ref>
*Irregular, decreased respirations (caused by impaired brainstem function)
*Bradycardia
*Systolic hypertension (with widening pulse pressure)<ref>{{cite book|last1=Caroline|first1=Nancy|title=Emergency Care in the Streets|date=2013|publisher=Jones and Bartlett Learning|isbn=978-1-4496-4151-1|page=1665|edition=7th}}</ref>
It is associated with an increase in [[intracranial pressure]].