Blood levels of histamine and norepinephrine in humans with sympathetic hyperactivity

The possible existence of a histaminergic pathway by which a reciprocal contralateral inhibitory modulation of the peripheral sympathetic nervous system is exerted motivated the present experimental clinical work. Blood levels of histamine (HA) and norepinephrine (NE) were measured in peripheral blood from patients with Tetanus or Guillain-Barre Syndrome (GBS), pathologies known to present sympathetic hyperactivity crisis in the course of its evolution; also in critically ill patients in general, hospitalized in Intensive Care Units (ICU); and in healthy voluntary donors from the Blood Banks. The results show that NE levels of Tetanus patients and those with GBS (336 and 326 pg/ mL, respectively) were significantly higher than those of the donors and critically ill patients in general (148 and 163 pg/mL, respectively), even without being found in a crisis of clinically detected sympathetic hyperactivity, denoting the existence of a state of basal sympathetic hyperactivity in these two pathologies. Meanwhile, HA levels in these groups ranged from 7 to 10 ng/mL and showed no significant differences between them. In conclusion, the levels of HA tend to keep a dual behaviour, in those conditions with possible peripheral modulator reflex unscathed, they raised simultaneously with the levels of NE, probably as the result of the expected physiological response to situations of sympathetic stimulation; and in patients who showed an exaggerated, uncontrolled sympathetic activity, we did not observe a corresponding rise in their levels, which could be interpreted as a deficit of the modulating response.

Paroxysmal Sympathetic Hyperactivity

Paroxysmal sympathetic hyperactivity (PSH) is a relatively common, but often unrecognized, complication of acute diffuse or multifocal brain diseases, most frequently encountered in young comatose patients with severe traumatic brain injury. It is presumed to be caused by loss of cortical inhibitory modulation of diencephalic and brain stem centers and possible additional maladaptive changes in the spinal cord that combine to produce exaggerated sympathetic responses to stimulation. The syndrome consists of repeated sudden episodes of tachycardia, tachypnea, hypertension, sweating, and sometimes fever and dystonic posturing. The diagnosis is clinical. Treatment includes reducing any external stimulation that can trigger the episodes, and starting abortive (e.g., intravenous morphine) and preventive medications (e.g., gabapentin, propranolol, clonidine). Prompt and adequate treatment of PSH may reduce the likelihood of secondary complications, such as dehydration, weight loss and malnutrition, and muscle contractures.

Voltage-sensitive dye imaging reveals inhibitory modulation of ongoing cortical activity

Voltage-sensitive dye imaging (VSDI) is a powerful technique for interrogating membrane potential dynamics in assemblies of cortical neurons, but with effective resolution limits that confound interpretation. In particular, it is unclear how VSDI signals relate to population firing rates. To address this limitation, we developed an in silico model of VSDI in a biologically faithful digital reconstruction of rodent neocortical microcircuitry. Using this model, we extend previous experimental observations regarding the cellular origins of VSDI, finding that the signal is driven primarily by neurons in layers 2/3 and 5. We proceed by exploring experimentally inaccessible circuit properties to show that during periods of spontaneous activity, membrane potential fluctuations are anticorrelated with population firing rates. Furthermore, we manipulate network connections to show that this effect depends on recurrent connectivity and is modulated by external input. We conclude that VSDI primarily reflects inhibitory responses to ongoing excitatory dynamics.