Technique and preliminary findings for in vivo quantification of brain motion during injurious head impacts.

Computational models of the human brain are widely used in the evaluation and development of helmets and other protective equipment. These models are often attempted to be validated using cadaver tissue displacements despite studies showing neural tissue degrades quickly after death. Addressing this limitation, this study aimed to develop a technique for quantifying living brain motion in vivo using a closed head impact animal model of traumatic brain injury (TBI) called CHIMERA. We implanted radiopaque markers within the brain of three adult ferrets and resealed the skull while the animals were anesthetized. We affixed additional markers to the skull to track skull kinematics. The CHIMERA device delivered controlled, repeatable head impacts to the head of the animals while the impacts were fluoroscopically stereo-visualized. We observed that 1.5 mm stainless steel fiducials (∼8 times the density of the brain) migrated from their implanted positions while neutral density targets remained in their implanted position post-impact. Brain motion relative to the skull was quantified in neutral density target tests and showed increasing relative motion at higher head impact severities. We observed the motion of the brain lagged behind that of the skull, similar to previous studies. This technique can be used to obtain a comprehensive dataset of in vivo brain motion to validate computational models reflecting the mechanical properties of the living brain. The technique would also allow the mechanical response of in vivo brain tissue to be compared to cadaveric preparations for investigating the fidelity of current human computational brain models.

On the reduction of spontaneous and glutamate-driven spinocerebellar and spinoreticular tract neuronal activity during active sleep.

The present study was performed to provide evidence that dynamic neural processes underlie the reduction in dorsal spinocerebellar tract and spinoreticular tract neuron activity that occurs during active sleep. To ascertain the effect of local inhibition on the spontaneous and glutamate-evoked spike discharge of sensory tract neurons, preliminary control tests were performed during the state of quiet wakefulness, where GABA or glycine was co-administered in a sustained fashion during pulsatile release of glutamate to dorsal spinocerebellar tract (n=3) or spinoreticular tract (n=2) neurons. Co-administration of GABA or glycine also resulted in a significant marked suppression of spontaneous spike activity and glutamate-evoked responses of these cells. Extracellular recording experiments combined with juxtacellular application of glutamate were then performed on 20 antidromically identified dorsal spinocerebellar tract and spinoreticular tract neurons in the chronic intact cat as a function of sleep and wakefulness. The glutamate-evoked activity of a group of 10 sensory tract neurons (seven dorsal spinocerebellar tract, three spinoreticular tract), which exhibited a significant decrease in their spontaneous spike activity during active sleep, was examined. Glutamate-evoked activity in these cells was significantly attenuated during active sleep compared with wakefulness. In contrast, the glutamate-evoked activity of a second group of eight sensory tract neurons (four dorsal spinocerebellar tract, four spinoreticular tract), which exhibited a significant increase in their spontaneous spike activity during active sleep, was not significantly altered in a state-dependent manner. These data indicate that, during natural active sleep, a dynamic neural process is engaged onto certain dorsal spinocerebellar tract and spinoreticular tract neurons, which in turn dampens sensory throughput to higher brain centers.

Spontaneous spike activity of spinoreticular tract neurons during sleep and wakefulness.

Sleep mentation studies infer that pain sensation in humans may be reduced during active REM sleep. However, to provide a mechanistic explanation for this phenomenon, few, if any neurophysiological studies have been performed at the lumbar level from neurons comprising classical pain pathways during sleep and wakefulness. The spinoreticular tract is one such classical pathway that has been implicated in the rostral transmission of nociceptive information. The present study was performed to determine if the activity of spinoreticular tract (SRT) neurons is dependent upon behavioral state. Accordingly, extracellular recording techniques were used to monitor the activity of identified SRT neurons in unanesthetized chronic cats during sleep and wakefulness. The ongoing spike activity of SRT neurons was found to be relatively uniform when the states of quiet wakefulness and quiet sleep were compared. However, during active sleep, the majority of the SRT neurons sampled underwent a sustained reduction in spike activity. Marked facilitation of SRT cell activity occurred in a few instances. These data provide the first unitary evidence supporting earlier evoked potential, psychophysical and clinical studies that ascending sensory information in a classical pain pathway is regulated in a state-dependent fashion.

State-dependent changes in glutamate, glycine, GABA, and dopamine levels in cat lumbar spinal cord.

Recent studies have indicated that the glycine receptor antagonist strychnine and the gamma-aminobutyric acid type A (GABA A) receptor antagonist bicuculline reduced the rapid-eye-movement (REM) sleep-specific inhibition of sensory inflow via the dorsal spinocerebellar tract (DSCT). These findings imply that the spinal release of glycine and GABA may be due directly to the REM sleep-specific activation of reticulospinal neurons and/or glutamate-activated last-order spinal interneurons. This study used in vivo microdialysis and high-performance liquid chromatography analysis techniques to provide evidence for these possibilities. Microdialysis probes were stereotaxically positioned in the L3 spinal cord gray matter corresponding to sites where maximal cerebellar-evoked field potentials or individual DSCT and nearby spinoreticular tract (SRT) neurons could be recorded. Glutamate, glycine, and GABA levels significantly increased during REM sleep by approximately 48, 48, and 14%, respectively, compared with the control state of wakefulness. In contrast, dopamine levels significantly decreased by about 28% during REM sleep compared with wakefulness. During the state of wakefulness, electrical stimulation of the nucleus reticularis gigantocellularis (NRGc) at intensities sufficient to inhibit DSCT neuron activity, also significantly increased glutamate and glycine levels by about 69 and 45%, respectively, but not GABA or dopamine levels. We suggest that the reciprocal changes in the release of glutamate, glycine, and GABA versus dopamine during REM sleep contribute to the reduction of sensory inflow to higher brain centers via the DSCT and nearby SRT during this behavioral state. The neural pathways involved in this process likely include reticulo- and diencephalospinal and spinal interneurons.

Tooth pulp- and facial hair mechanoreceptor-evoked responses of trigeminal sensory neurons are attenuated during ketamine anesthesia.

BACKGROUND: Evidence exists that ketamine, administered systemically using a dose required for inducing a state of anesthesia, may antagonize nociceptive but not innocuous input to lumbar dorsal horn neurons. However, it is unclear whether ketamine exerts this selective action on sensory inputs to trigeminal sensory neurons. The current study was undertaken to compare the responses evoked in trigeminal sensory neurons by electrical stimuli applied to the tooth pulp versus air-puff stimuli applied to facial hair mechanoreceptors (FHMs) during quiet wakefulness versus ketamine anesthesia. METHODS: Accordingly, responses of rostral trigeminal sensory nuclear complex (TSNC) and trigeminothalamic tract neurons evoked by tooth pulp (a source of small-diameter fiber input) and FHMs (a source of larger-diameter fiber input) were recorded extracellularly from chronically instrumented cats before, during, and after recovery from the anesthetic state induced by a single (2.2 mg/kg) intravenous injection of ketamine. RESULTS: Overall, tooth pulp-evoked responses of TSNC neurons were maximally suppressed by 50% within 5 min after the intravenous administration of ketamine. Ketamine also suppressed the FHM-evoked responses of TSNC and trigeminothalamic neurons by 45%. The time course of ketamine's suppressive action was equivalent for tooth pulp- and FHM-evoked responses. However, the recovery of tooth pulp-evoked TSNC neuronal responses at suprathreshold intensities was markedly prolonged compared with neuronal responses driven by threshold stimuli or FHM. CONCLUSIONS: These electrophysiologic results in the chronically instrumented cat preparation indicate that a nonselective suppression of orofacial somatosensory information occurs during ketamine anesthesia. The prolonged recovery of suprathreshold responses of TSNC neurons mediated by small-diameter afferent fiber input may partly underlie the analgesic action of ketamine that is clinically relevant at subanesthetic doses.

Spontaneous discharge and peripherally evoked orofacial responses of trigemino-thalamic tract neurons during wakefulness and sleep.

In the present study, ongoing and evoked activity of antidromically identified trigemino-thalamic tract (TGT) neurons was examined over the sleep-wake cycle in cats. There was no difference in the mean spike discharge rate of TGT neurons when quiet sleep (QS) and active sleep (AS) were compared with wakefulness (W). However, tooth pulp-evoked responses of TGT neurons were decreased during AS when compared to W. Conversely, the responses of TGT neurons to air puff activation of facial hair mechanoreceptors reciprocally increased during AS when compared to W. The present data demonstrate that ascending sensory information emanating from distinct orofacial areas is differentially modified during the behavioral state of AS. Specifically, the results obtained suggest that during AS, sensory information arising from hair mechanoreceptors is enhanced, whereas information arising from tooth pulp afferents is suppressed. These data may provide functional evidence for an AS-related gate control mechanism of sensory outflow to higher brain centers.