Oxygen‐conserving reflexes of the brain: the current molecular knowledge

Abstract

The trigemino-cardiac reflex (TCR) may be classified as a sub-phenomenon in the group of the so-called ‘oxygen-conserving reflexes’. Within seconds after the initiation of such a reflex, there is neither a powerful and differentiated activation of the sympathetic system with subsequent elevation in regional cerebral blood flow (CBF) with no changes in the cerebral metabolic rate of oxygen (CMRO2) or in the cerebral metabolic rate of glucose (CMRglc). Such an increase in regional CBF without a change of CMRO2 or CMRglc provides the brain with oxygen rapidly and efficiently and gives substantial evidence that the TCR is an oxygen-conserving reflex. This system, which mediates reflex protection projects via currently undefined pathways from the rostral ventrolateral medulla oblongata to the upper brainstem and/or thalamus which finally engage a small population of neurons in the cortex. This cortical centre appears to be dedicated to reflexively transduce a neuronal signal into cerebral vasodilatation and synchronization of electrocortical activity. Sympathetic excitation is mediated by cortical-spinal projection to spinal pre-ganglionic sympathetic neurons whereas bradycardia is mediated via projections to cardiovagal motor medullary neurons. The integrated reflex response serves to redistribute blood from viscera to brain in response to a challenge to cerebral metabolism, but seems also to initiate a preconditioning mechanism. Better and more detailed knowledge of the cascades, transmitters and molecules engaged in such endogenous (neuro) protection may provide new insights into novel therapeutic options for a range of disorders characterized by neuronal death and into cortical organization of the brain.

The Trigeminocardiac Reflex in Neurological Disorders

“…Its occurrence can lead to varied clinical presentations ranging from bradycardia and hypotension to complete asystole and/or apnea. [1][2][3][4][5][6][7][8] Because of these potentially life-threatening complications, the TCR has gained enormous and increasing attention during the last several years.…”

“…[1][2][3][4][5][6][7][8] The proposed reflex arc involves the stimulation of sensory nerve endings-the sensory branches of the trigeminal nerve that carry neuronal signals to the sensory nucleus of the trigeminal nerve via the Gasserian ganglion, which forms the afferent pathway of the reflex arc. [1][2][3][4][5][6][7][8] The internuncial nerve fibers in the reticular formation connect the sensory nucleus…”

Trigeminocardiac Reflex: Beyond a skull base Reflex

“…The TCR has developed from a phenomenon during skull base surgery to a perioperative factor influencing the outcome after skull base surgeries/interventions [2,13,14,25,[27][28][29]. This was already a milestone in neurosciences during the last 20 years.…”

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“…Cytolytic viruses and genes coding for antitumor cytokines, prodrug-converting enzymes and various neurotrophic factors have all been engineered into engraftable NSCs for delivery to tumors (1). Novel brain tumor treatment strategies that involve transplantation or infusion of cells that seek out invading tumor cells demand thorough in vivo monitoring (3)(4)(5)(6)(7)(8)15,16). In particular, NSCs have attracted great interest because they have demonstrated tropism to tumor cells and even long-distance migration to single tumor cells (17,18).…”