Consciousness monitoring using near-infrared spectroscopy (NIRS) during high +Gz exposures.

The relationship between human consciousness and oxygen saturation (rSO(2)) in cerebral tissue under high +Gz stress was non-invasively monitored by near-infrared multiple wavelength spectroscopy (NIRS). We studied the drop in rSO(2) levels in human subjects during exposure to various head-to-foot acceleration (+Gz) profiles. These profiles included sustained +Gz plateaus and repeated short duration +Gz pulses of varying duration. The end point in this study was +Gz-induced loss of consciousness (G-LOC). The rSO(2) levels under normal (asymptomatic), almost loss of consciousness (A-LOC) and G-LOC conditions were recorded. Correlations among decrease in rSO(2), +Gz pulse duration, +Gz stress level and incapacitation time (ICAP) after G-LOC were also investigated. It was found that once rSO(2) fell to a certain level, G-LOC occurred. This threshold was repeatable and independent of the +Gz level or duration. It was also observed that the total ICAP after G-LOC was dependent on the length of time that rSO(2) remained below the G-LOC threshold level, i.e. the longer the rSO(2) level remained below the G-LOC induction level, the longer the subject remained unconscious. These results may prove to be useful in designing closed loop control systems for personal protective gear for pilots of high performance aircraft.

Low dose pramipexole is neuroprotective in the MPTP mouse model of Parkinson's disease, and downregulates the dopamine transporter via the D3 receptor.

BACKGROUND: Our aim was to determine if pramipexole, a D3 preferring agonist, effectively reduced dopamine neuron and fiber loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model when given at intraperitoneal doses corresponding to clinical doses. We also determined whether subchronic treatment with pramipexole regulates dopamine transporter function, thereby reducing intracellular transport of the active metabolite of MPTP, 1-methyl-4-phenylpyridinium (MPP+). METHODS: Ten 12-month old C57BL/6 mice were treated with MPTP (or saline) twice per day at 20 mg/kg s.c. (4 injections over 48 h). Mice were pretreated for 3 days and during the 2-day MPTP regimen with pramipexole (0.1 mg/kg/day) or saline. Stereological quantification of dopamine neuron number and optical density measurement of dopamine fiber loss were carried out at 1 week after treatment, using immunostaining for dopamine transporter (DAT) and tyrosine hydroxylase (TH). Additional wild-type (WT) and D3 receptor knockout (KO) mice were treated for 5 days with pramipexole (0.1 mg/kg/day) or vehicle. The kinetics of [3H]MPP+ and [3H]DA uptake (Vmax and Km) were determined 24 h later; and at 24 h and 14 days dopamine transporter density was measured by quantitative autoradiography. RESULTS: Pramipexole treatment completely antagonized the neurotoxic effects of MPTP, as measured by substantia nigra and ventral tegmental area TH-immunoreactive cell counts. MPTP- induced loss of striatal innervation, as measured by DAT-immunoreactivity, was partially prevented by pramipexole, but not with regard to TH-IR. Pramipexole also reduced DAT- immunoreactivity in non-MPTP treated mice. Subchronic treatment with pramipexole lowered the Vmax for [3H]DA and [3H]MPP+ uptake into striatal synaptosomes of WT mice. Pramipexole treatment lowered Vmax in WT but not D3 KO mice; however, D3 KO mice had lower Vmax for [3H]DA uptake. There was no change in DAT number in WT with pramipexole treatment or D3 KO mice at 24 h post-treatment, but there was a reduction in WT-pramipexole treated and not in D3 KO mice at 14 days post-treatment. CONCLUSION: These results suggest that protection occurs at clinically suitable doses of pramipexole. Protection could be due to a reduced amount of MPP+ taken up into DA terminals via DAT. D3 receptor plays an important role in this regulation of transporter uptake and availability.

Acceleration-induced near-loss of consciousness: the "A-LOC" syndrome.

BACKGROUND: There is an insidious phenomenon that can occur when aircrew are exposed to +Gz stress even at levels that are insufficient to cause +Gz-induced loss of consciousness (G-LOC). Under these circumstances aircrew exhibit an altered state of awareness that was termed Almost Loss of Consciousness (A-LOC) by the U.S. Navy in the late 1980's. A-LOC is a syndrome that includes a wide variety of cognitive, physical, emotional, and physiological symptoms. While A-LOC has been observed in centrifuge studies and reported in flight for over 15 yr, a definitive description of the syndrome does not exist. METHODS: Nine subjects were exposed to short +6, 8, and 10 Gz pulses of increasing duration until they experienced G-LOC. Instrumentation included two channels of ECG and near infrared spectroscopy (NIRS) to measure relative cerebral tissue oxygenation (rSo2). Subjects indicated +Gz-induced visual symptoms (light loss, LL) by pressing a switch when LL began and releasing it when total vision was restored. Short-term memory loss was assessed using a simple math task. Data analysis included a description and the time course of the physical, physiological, cognitive, and emotional responses. RESULTS: There were 66 episodes of A-LOC that were identified out of a total of 161 +Gz pulse exposures. Many incidents of sensory abnormalities, amnesia, confusion, euphoria, difficulty in forming words, and reduced auditory acuity were documented. Often these responses occurred in multiple subjects and at different +Gz levels. One of the most common symptoms was a disconnection between cognition and the ability to act on it. There was a significant reduction in rSo2 over baseline, greater overshoot in rSo2 (increase in oxygenation above baseline after the +Gz exposure), faster fall in rSo2 during +Gz stress, and prolonged recovery time associated with A-LOC as compared with +Gz exposures without symptoms. CONCLUSION: Evaluation of the range of symptoms associated with A-LOC can lead to a program to increase pilots' awareness of the phenomenon and further our understanding of the relationship between the outward symptoms and the underlying physiological changes.

Noninvasive monitoring of human consciousness by near-infrared spectroscopy (NIRS) during high +Gz stress.

Noninvasive monitoring of the relative change in oxygen saturation (rSO2) in cerebral tissue by near-infrared multi-wavelength spectroscopy (NIRS) was investigated in humans under high acceleration (+Gz) stress. These profiles included sustained 15-second +Gz plateaus and repeated short duration +Gz pulses of varying duration. The end points in this study were loss of consciousness due to high +Gz exposure (GLOC). In many cases subjects demonstrated cognitive and physical symptoms related to reduced cerebral blood flow without frank unconscious, which has been called Almost Loss of Consciousness (ALOC). Both the rSO2 levels during and after the +Gz exposures and the total time subjects were incapacitated after GLOC were recorded. It was found that while the drop in rSO2 at the onset of GLOC was lower during pulse exposures as compared to sustained exposures, the total time to recovery from GLOC was longer during the sustained runs. By applying a better understanding of the nature and timing of +Gz-induced changes in cerebral tissue oxygenation, more efficient control systems for personal protective gear for pilots of high performance aircraft can be implemented.