The effects of physical vibration on heart rate variability as a measure of drowsiness.

We investigated the effects of low frequency whole body vibration on heart rate variability (HRV), a measure of autonomic nervous system activation that differentiates between stress and drowsiness. Fifteen participants underwent two simulated driving tasks for 60 min each: one involved whole-body 4-7 Hz vibration delivered through the car seat, and one involved no vibration. The Karolinska Sleepiness Scale (KSS), a subjective measure of drowsiness, demonstrated a significant increase in drowsiness during the task. Within 15-30 min of exposure to vibration, autonomic (sympathetic) activity increased (p < .01) in response to the stress of maintaining alertness and performance when drowsy, and peaked at 60 min (p < .001). Changes in three other HRV domains [higher LF/HF ratios, lower RMSSD (ms) and pNN50 (%) values] were consistent with increased sympathetic activation. These findings have implications for the future development of equivalent drowsiness contours leading to improvements in road safety. Practitioner summary: The effects of physical vibration on driver drowsiness have not been well investigated. This laboratory-controlled study found characteristic changes in heart rate variability (HRV) domains that indicated progressively increasing neurological effort in maintaining alertness in response to low frequency vibration, which becomes significant within 30 min. ABBREVIATIONS: ANS: autonomic nervous system; Ctrl: control; EEG: electroencephalography; HF: the power in high frequency range (0.15 Hz-0.4Hz) in the PSD relected parasympathetic activity only; HRV: heart rate variability; KSS: karolinska sleepiness scale; LF: the power in low frequency range (0.04 Hz-0.15Hz) in the PSD reflected both sympathetic and parasympathetic activity of the autonomic nervous system; LF/HF ratio: the ratio of LF to HF indicated the balance between sympathetic and parasympathetic activity; RMSSD: the root mean square of difference of adjacent RR interval; pNN50: the number of successive RR interval pairs that differed by more than 50 ms divided by the total number of RR intervals; RR interval: the differences between successive R-wave occurrence times; PSD: power spectral density; RTP: research training program; SD: standard deviation; SEM: standard error of the Mean; Vib: vibration.

Incomplete Freund's adjuvant enhances locomotor performance following spinal cord injury.

Following spinal cord injury (SCI), the pathological sequelae which ensue through the secondary mechanisms of degeneration produce myelin deposits which are potent inhibitors of endogenous neuroregeneration. We have enhanced the immune-mediated response following a hemisection lesion by immunizing adult C57Bl/6 female mice against the inhibitor of neurite outgrowth Nogo-A(623-640) peptide. Moderate anti-Nogo-A(623-640) antibody titre levels were obtained by using Montanide as the adjuvant. However, this antibody response was not obtained using incomplete Freund's adjuvant (IFA). Significant benefit in locomotor performance was demonstrated only in animals which were vaccinated with IFA and not with Montanide. No further benefit could be demonstrated with the Nogo-A(623-640) peptide beyond that seen for adjuvant alone. These data imply that generating antibodies against Nogo-A(623-640) in vivo alone is not sufficient to enhance locomotor recovery and that subcutaneous injection of IFA prior to SCI can enhance locomotor performance.

Induction of endogenous neural precursors in mouse models of spinal cord injury and disease.

Adult neural precursor cells (NPCs) in the mammalian central nervous system (CNS) have been demonstrated to be responsive to conditions of injury and disease. Here we investigated the response of NPCs in mouse models of spinal cord disease [motor neuron disease (MND)] with and without sciatic nerve axotomy, and spinal cord injury (SCI). We found that neither axotomy, nor MND alone brought about a response by Nestin-positive NPCs. However, the combination of the two resulted in mobilization of NPCs in the spinal cord. We also found that there was an increase in the number of NPCs following SCI which was further enhanced by systemic administration of the neuregulatory cytokine, leukaemia inhibitory factor (LIF). NPCs were demonstrated to differentiate into astrocytes in axotomized MND mice. However, significant differentiation into the various neural cell phenotypes was not demonstrated at 1 or 2 weeks following SCI. These data suggest that factors inherent to injury mechanisms are required for induction of an NPC response in the mammalian spinal cord.

Effects of intraperitoneal injection of Rofecoxib in a mouse model of ALS.

There is increasing evidence that inflammatory mechanisms are involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). Inhibition of a key mediator of inflammation, cyclooxygenase 2 (COX-2), represents a promising therapeutic approach in ALS. Here we tested the in vivo effects of a specific COX-2 inhibitor, Rofecoxib, administered by intraperitoneal injection, in the SOD1(G93A G1H) mouse model of the familial form of ALS (fALS). Rofecoxib administration commenced at postnatal day 60 (P60), since the hallmarks of inflammation in the spinal cord were found to occur beyond this time-point in this mouse model of fALS. We found a significant but small delay in the onset of locomotor impairment in mice treated with Rofecoxib at the dose of 10 mg/kg of weight. However, survival was not effected by treatment. As prostaglandin E2 levels in spinal cord or in plasma were not reduced by Rofecoxib treatment, these results may suggest lack of sufficient bioavailability as the reason for the modest clinical changes observed.

Leukemia inhibitory factor by systemic administration rescues spinal motor neurons in the SOD1 G93A murine model of familial amyotrophic lateral sclerosis.

Leukemia inhibitory factor (LIF) is a survival factor for motoneurons. In this study we investigated whether intense systemic LIF therapy prevents the loss of lumbar motoneurons in the transgenic SOD1 G93A mouse model of familial amyotrophic lateral sclerosis. Treatment involved daily 25 microg/kg intraperitoneal injection for a period of 6 weeks starting at 70 days of age. Using the unbiased optical dissector technique, significant rescue of motoneurons in the LIF-treated group (3809+/-455) was found compared to the vehicle group (1085+/-140).