Biomechanical and electromyogram characterization of neuroleptic-induced rigidity in the rat.

Rodent models of Parkinson's disease (PD) are usually assessed using measures of akinesia, but other important parkinsonian symptoms such as rigidity are only rarely quantified. This is in part due to technical difficulties in obtaining such measures in small animals. In the present study we developed quantitative methods to provide time-course assessment of the alternations of muscle tone of parkinsonian rats. A portable and miniature biomechanical stretching device was established to manually stretch the hindlimb of awake rats with muscle rigidity induced by dopamine D2-receptor antagonist raclopride (5 mg/kg, i.p.). From the measured angular displacement angle and reactive torque of sinusoidal stretches at five varied frequencies, viscoelastic components of the muscle tone can be derived. In addition, non-invasive multielectrode was applied to record the tonic and phasic components of the gastrocnemius muscle electromyogram (EMG). Our biomechanical measurements showed not only increase in stiffness (P<0.05) but also increase in viscous components (P<0.05) that matched the time course of increased amplitude of EMG activity (P<0.05). There was a significant positive correlation between all of these measures and akinesia, as measured by the conventional bar-test for catalepsy (with a correlation coefficient of 0.87 at stiffness, 0.92 at viscosity and 0.96 at amplitude of EMG). Phasic contraction counts (PCC) of voluntary EMG exhibited a significantly negative correlation with the bar test scores (correlation coefficient=-0.78). These results confirm that akinesia induced by D2-receptor blockade also induces a rigidity that shares many features with human PD. These novel techniques for quantifying biomechanical and electromyographic parameters provide objective assessment methods for investigating the time-course changes of abnormal muscle tone in rat models of PD that will be useful for evaluating novel treatments.

Time course quantification of spastic hypertonia following spinal hemisection in rats.

Progressive changes in the muscle tone and stretch reflex after spinal cord injury (SCI) provide insight into the time-course development of spasticity. This study quantified the time-course changes of hypertonia for rats following SCI of T8 hemisection. A miniature manual stretching device measured the reactive torque via a pair of pressure sensing balloons; the angular displacement was measured via an optoelectronic device. Various stretching frequencies were tested, specifically 1/3, 1/2, 1, 3/2 and 2 Hz. The reactive torque and angular displacement were used to derive the viscous and elastic components representing the viscosity and stiffness of the rat's ankle joint. The enhanced velocity-dependent properties of spasticity were observed in the SCI hemisection rats (n=9) but not in the controls (n=9). Time-course measurements from pre-surgery to 56 days following SCI showed that the muscle tone of the hemisection rats dropped immediately after spinal shock and then gradually increased to reach a peak around 21 days postinjury (P<0.01). The muscle tone remained at least 75% of the peak value up to the end of an 8 week observation period (P<0.05). The changes of muscle tone can also be verified from the electrophysiological evaluations of electromyography (EMG) (P<0.05). In addition to conventional BBB motor behavior score, our results provided time-course quantification of the biomechanical and electrophysiological properties of muscle tone from the onset of SCI. Such data are useful for investigating progressive recovery of spinal damage in animal model and for future objective assessment of improved treatment for SCI human subjects.

Regulation of hind-limb tone by adenosine A2A receptor in rats.

Adenosine A2A receptor agonists produce a hypokinetic state (catalepsy) that is believed to reflect antagonistic interaction of A2A and dopamine D2 receptors in the basal ganglia. In addition to catalepsy, pharmacological blockade of D2 receptors produces rigidity. However there are conflicting data about the effect of A2A agonists on muscle tone, with some reports indicating an increase, while other data suggest that A2A catalepsy is dominated by muscle hypotonia. We investigated the effect on resistance to imposed movements of systemic cataleptic doses of the selective A2A agonist CGS21680 (5 mg/kg), and compared it with the effect of the D2 antagonist raclopride (5 mg/kg), in rats. Total resistance is made up of elastic and viscous components. The elastic component is velocity independent, and is referred to as "stiffness," whereas viscosity, which dampens responses to imposed movements, is velocity dependent. Using a method for quantifying total joint resistance that enabled separate identification of stiffness and viscosity, we found that during catalepsy evoked by either drug there was a clear increase in joint rigidity. Both CGS21680 and raclopride significantly increased joint stiffness, the velocity independent component of rigidity that is most affected in Parkinsonism. In contrast, the effect of CGS21680 on the velocity-dependent viscosity component was less robust than for raclopride, and did not reach significance, possibly reflecting an interaction with sedative effects via extrastriatal receptors. The effect of CGS21680 and raclopride on joint stiffness is thus consistent with previous findings suggesting functional antagonism of A2A and D2 receptors in the basal ganglia.

Quantitative analysis of the velocity related pathophysiology of spasticity and rigidity in the elbow flexors.

OBJECTIVE: To quantify velocity dependent and position related properties of increased muscle tone measured during a constant velocity stretch. METHODS: Elbow flexors were vertically stretched under four different velocities (40, 80, 120, and 160 degrees /s) through a 75 degrees range of motion in 12 patients with hemiparesis, 16 with parkinsonism, and 12 normal controls. From reactive torque measurement, a linear second order model was adopted to dissociate velocity dependent viscous and velocity independent elastic components. The averaged speed dependent reflex torque (ASRT)--defined as the deviation of measured torque from baseline torque--was used to quantify the viscous component of hypertonia. Velocity sensitivity of ASRT (VASRT) and segmented ASRT (SASRT), derived from the slope of the regression line among ASRT velocity plots and from segmentations of reactive torque, respectively, were used to differentiate the increased muscle tone of spasticity and rigidity. RESULTS: ASRT and VASRT were significantly higher in both spasticity and rigidity than in normal controls. SASRT analysis showed three different position related patterns among spasticity, rigidity, and normal groups: spasticity showed progressively increasing muscle tension relative to position; rigidity showed increased (relative to the norm) but constant muscle tone over the entire stretch range; the normal control group showed a consistently low reactive torque over the entire range. CONCLUSIONS: Velocity dependence analysis indicates that rigidity and spasticity have approximately equal velocity dependent properties. For differentiating these two types of hypertonia, position dependent properties my be employed.

A multi-functional online measurement system for neuron-microelectrode interface study.

The goal of this paper is to develop a multifunctional measurement system for neuron-microelectrode interface study by LabVIEW. The system uses a commercial 60-channel microelectrode array (MEA) as an interface platform. These online functions of neuronal stimulation, extracellular potential recording, impedance monitoring, and data storage have been integrated into this system. Two offline analysis functions of wavelet de-noising and artifact removing are also included. The former two online functions are executed respectively by a NI-DAQ card and by a self-made analog frond-end amplifier, and Agilent 4284A LCR meter makes the impedance measurement. We have completed the basic functional verifications on a cultured MEA with PC-12.