Sprouting and reflex recovery after spinal nerve lesions in cats

The contribution of L7 spinal nerve to the innervation of tibialis anterior muscle varies with the anatomic arrangement of the lumbosacral plexus. When the plexus is “prefixed”, L7 shares the innervation of tibialis anterior with L6 and S1. “Postfixation” of the plexus results in exclusion of L7 from the innervation of tibialis anterior. L5, L6, and S1 and S2 were cut unilaterally in 22 cats. Postoperatively, in cats with prefixed plexus the tendon reflex of tibialis anterior was initially weak. Methylene blue staining revealed both normal and degenerating nerves to tibialis anterior. The reflex became stronger during the first week. At that time an increased number of motor end-plates per axon was found. In operated cats with postfixed plexus, the tibialis reflex was abolished. No normal (nondegenerating) nerves or motor end-plates were seen. During the second week the abolished reflex returned. Some axons were now seen in the intramuscular nerve of tibilis anterior. They contained abnormal knot-like structures from which increased numbers of fibers extended. Some of these ended in single, normal-appearing motor end-plates. Reflex recovery can thus be associated with sprouting of peripheral nerves of two types: “homonymous” sprouting of nerves already within a partially denervated muscle occurs rapidly (first week) and may mediate increased strength of a weakened reflex; “heteronymous” sprouting of nerves outside the denervated muscle occurs more slowly (second week) and may mediate the return of a reflex initially abolished by the lesion.     

Bladder and urethral sphincter responses evoked by microstimulation of S2 sacral spinal cord in spinal cord intact and chronic spinal cord injured cats

Urinary bladder and urethral sphincter responses evoked by bladder distention, ventral root stimulation, or microstimulation of S2 segment of the sacral spinal cord were investigated under alpha-chloralose anesthesia in cats with an intact spinal cord and in chronic spinal cord injured (SCI) cats 6-8 weeks after spinal cord transection at T9-T10 spinal segment. Both SCI and normal cats exhibited large amplitude reflex bladder contractions when the bladder was fully distended. SCI cats also exhibited hyperreflexic bladder contractions during filling and detrusor-sphincter dyssynergia during voiding, neither was observed in normal cats. Electrical stimulation of the ventral roots revealed that the S2 sacral spinal cord was the most effective segment for evoking large amplitude bladder contractions or voiding in both types of cats. Microstimulation with a stimulus intensity of 100 microA and duration of 30-60 s via a single microelectrode in the S2 lateral ventral horn or ventral funiculus evoked large amplitude bladder contractions with small urethral contractions in both normal and SCI cats. However, this stimulation evoked incomplete voiding due to either co-activation of the urethral sphincter or detrusor-sphincter dyssynergia. Stimulation in the S2 dorsal horn evoked large amplitude sphincter responses. The effectiveness of spinal cord microstimulation with a single electrode to induce prominent bladder and urethral sphincter responses in SCI animals demonstrates the potential for using microstimulation techniques to modulate lower urinary tract function in patients with neurogenic voiding dysfunctions.     

Thermoregulatory responses of decerebrate and spinal cats

Cooling the spinal cord of the unanesthetized cat elicited shivering, piloerection, and vasoconstriction. A high-level decerebration abolished these effects. Lowering the decerebration to the level of the lower pons or medulla reinstated these responses to spinal cord cooling. In unanesthetized chronic spinal cats, cooling the spinal cord below the level of a T6 transection produced similar thermoregulatory effects limited to the hind limbs, although it was of less intensity and without piloerection. A high-level decerebration abolished shivering in the forelimbs to whole body cooling, while permitting shivering below the level of transection to spinal cord cooling. Lowering the level of decerebration to the lower pons or medulla reinstated shivering, vasoconstriction, and piloerection in the forelimbs. The data suggest that there is a region in the midbrain and upper pontine tegmentum which exerts tonic inhibition on lower regions in the lower pons, medulla, and spnal cord. When released from inhibition these lower regions are capable of facilitating thermoregulatory responses. Such an organization resolves contradictory reports on the abolition of thermoregulation after decerebration and answers the question of why spinal cord cooling produces shivering in spinal preparations but not in decerebrate preparations.     

Forelimb responses to cutaneous nerve stimulation during locomotion in intact cats

The reflex responses of forelimb muscles to electrical stimulation of the cutaneous superficial radial nerve were recorded during treadmill locomotion in chronically implanted cats. In brachialis and cleidobrachialis (muscles which are active mainly during the swing phase) the responses were maximal during the swing phase and minimal or absent during the stance phase. In the long head of triceps which is active mainly during the stance phase, responses were also minimal during stance and maximal during swing. It is concluded that, for some muscles, the period of maximal reflex responsiveness can be out of phase with the period of the step cycle during which they are normally active.     

The dendritic tree of spinal neurons in dogs with experimental hind-limb rigidity

The dendritic tree of lumbosacral neurons from dogs with experimental hind-limb rigidity, produced by temporary lumbosacral ischemia, was reduced to about one-third of the mean normal size, as previously established in Golgi-Kopsch preparations. The size reduction was due to the loss only of the more distal segments of the tree by the neurons which survived the ischemic episode, thus decreasing the mean radius of the dendritic projections. The mean number of primary dendrites/neuron remained essentially the same as in the normal but the portions extending beyond about 100 μ from cell body, and all their branches, suffered truncation: the branches originating closer to the cell body suffered the same truncation beyond the 100 μ border. The mean perikaryon size and size range in the sample of 300 neurons from three rigid dogs was not reduced from that of the 360 neuron sample from three normal animals. The loss of nearly two-thirds of dendrite surface, with consequent loss of all contacts with other neurons normally handled by this major fraction of the dendritic tree, compounded the denervation and isolation sustained by the cell body and surviving proximal part of the tree, due to the marked mortality of interneurons during the ischemic episode. The reduction of the mean of the calculated synaptic endings/neuron for the entire sample to less than one-fifth of normal and the narrowing of the range of synaptic populations/neuron to one-seventh of normal are some indications of the magnitude and consequences of this morphological alteration; an alteration concomitant with the demonstrated functional alterations in such neurons. The orderliness of the dendrite organization, as found in the sample of normal neurons, however, did not change to randomness in the altered, ?spastic”? ones. The peripheral portion of the dendritic arborization failed to survive the denervation and was promptly sloughed, it is postulated, because of its greater vulnerability to denervation, due to a greater dependency upon a continuous transneuronal supply of neurotrophic factors. This dependency may increase exponentially with increasing distance of dendrite segments from cell body. The concept of neuronal interdependence (Gelfan, '64) is extended to include viability of at least part of the dendritic tree.     

Effects of dorsolateral spinal lesions on stretch reflex threshold and stiffness in awake cats

Measurements of threshold angle and incremental dynamic stiffness (IDS) were derived from triceps surae stretch reflexes, elicited by ramp and hold flexion at the ankle joint of four cats that were tested while awake. Stretch reflexes were assessed from trials that began from different ankle joint start positions or were matched using a post-hoc analysis for initial background force during testing sessions before and following unilateral lesions of the dorsolateral funiculus at levels ranging from T13 to L3. Unilateral lesions of the dorsolateral funiculus (DLF) produced significant ipsilateral decreases in stretch reflex threshold and increases in reflex gain, measured as incremental dynamic stiffness (IDS). ancova testing indicated that the reduction in threshold, but not the increase in IDS, was dependent upon the level of background force. Reflex testing from different start angles demonstrated that DLF lesions diminished the correlation between threshold and IDS. Intravenous infusion of ketamine dose-dependently reduced IDS, compared with testing in the unanaesthetized state. Postoperative reflex testing during infusion of ketamine at 22.2 mg/kg per h, when electromyographic responses were reduced to 24% of control levels, abolished differences in IDS between the ipsilateral and contralateral hindlimbs. These and related observations suggest that the postoperative increase in IDS in awake animals was not due to an increase in passive stiffness.     

Cognitive function is largely intact in methadone maintenance treatment patients

Objectives: To confirm our previous findings of less cognitive impairments (based on cognitive screening tools) among methadone maintenance treatment (MMT) patients who achieved take-home dose (THD) privileges.

Methods: a random sample of 65 Israeli MMT patients were studied using computerised, age and education standardised, cognitive domains (attention, executive function, memory, motor skills), and non-computerised phonetic and semantic verbal fluency.

Results: Cognitive scores were within?±1 standard deviation (SD) of average for most domains, including non-verbal IQ, attention and motor skills. Verbal fluency and memory were?>1 SD below average (mean?=?84; z?=?–1.1 for both). Females were younger than the males and had poorer motor skills (P?=?0.005) but better verbal memory (P?P?=?0.05) and inversely with verbal memory (P?=?0.01). Overall cognitive function was poorest among 25 (38.5%) current drug users, and 6 (9.2%) lifetime schizophrenia patients. Cognitive domains were comparable between THD privileges subgroups.

Conclusions: Despite heterogeneity in MMT duration, abuse duration, substance use and psychiatric comorbidity, all performed within?±1 SD of average for age and education in most cognitive domains. Our findings challenge the notion of MMT as being synonymous with compromised cognition and may lead to reduced bias regarding cognitive function of MMT patients.     

Pudendal-to-bladder reflex in chronic spinal-cord-injured cats

The effects of pudendal nerve stimulation on reflex bladder activity were investigated in cats with chronic spinal cord injury (6-12 months) under alpha-chloralose anesthesia. Electrical stimulation of the pudendal nerve on one side at different frequencies and intensities induced either inhibitory or excitatory effects on bladder activity. The inhibitory effect peaked at a stimulation frequency of 3 Hz and gradually decreased at lower or higher frequencies. The inhibitory effect could occur at stimulation intensities between 0.3 and 1 V (pulse width 0.1 ms) and increased at intensities up to 10 V. Stimulation of the central end of transected pudendal nerve also inhibited bladder activity, indicating that afferent axons in pudendal nerve are involved. Nerve transections also showed that both hypogastric and pelvic nerves might be involved in the inhibitory pudendal-to-bladder spinal reflex. Pudendal nerve stimulation at 20 Hz and at the same intensities (1-10 V) elicited a bladder excitatory response. Although this excitatory effect could not sustain a long lasting bladder contraction at small bladder volumes, it did induce continuous rhythmic bladder contractions at large bladder volumes. This study indicated the possibility of developing a neuroprosthetic device based on pudendal nerve electrical stimulation to restore micturition function after spinal cord injury.     

Method for stable intracellular recordings of spinal alpha-motoneurons during treadmill walking in awake, intact cats

A method is described for recording from spinal alpha-motoneurons, which are identified according to muscle innervated, with an intracellular microelectrode during treadmill walking in awake, normally respiring, intact, adult cats. The procedure involves the implantation of an orthopedic-style spinal unit, the training of the subject to locomote on the treadmill with the lumbar region restrained, and the micropipette recording of motoneurons through a small laminotomy.     

Unrestrained walking in cats with partial spinal lesions

In four cats with partial spinal lesions, performed at a low thoracic level, involving ventral quadrants and, to a different extent, the dorsolateral funiculi, several parameters of locomotion were analyzed during unrestrained walking at moderate speed (0.3–1.0 m/s). Special attention was paid to the analysis of support patterns and the durations of support phases in step cycles. The operated subjects displayed a much greater variability of support patterns than intact cats as well as changes in the relative duration of some support phases. The most striking difference was an increase in the relative duration of support on two homolateral limbs accompanied by a reduction of support on diagonal limbs. These changes were mainly due to an impairment of fore-hindlimb coordination as shown by an increase in the phase shifts between the movements of diagonal limbs. Other parameters of locomotion were essentially unaltered, except for cats in which the lesion destroyed bilaterally major portions of the dorsolateral funiculi.     

Serotonergic modulation of spinal ascending activity and sacral reflex activity evoked by pelvic nerve stimulation in cats

Serotonin (5-HT) may be inhibitory to micturition at a spinal level. A potential mechanism of action for serotonergic inhibition of bladder function is a depression of the ascending limb of the supraspinal reflex mediating micturition. Ascending activity evoked by pelvic nerve stimulation was recorded in the thoracic spinal cord of anesthetized cats. For comparison, spinal reflex activity evoked by pelvic nerve stimulation was recorded on the pudendal nerve. The effects of intrathecal administration of serotonergic agents were examined to determine whether spinal and supraspinal responses to bladder afferent activation were modulated by 5-HT. Methysergide (60 nmol), a non-selective serotonergic antagonist, increased ascending activity by 61±7% and depressed spinal reflex activity by 38±6%. Zatosetron (10 nmol), a 5-HT₃ antagonist had a similar effect on both activities (increased by 93±24% and decreased by 77±7%, respectively). The effect on ascending activity of blocking 5-HT₃ receptors was also confirmed with ICS 205930 and MDL 72222. 2-Methyl-5-HT (800 nmol), a 5-HT₃ agonist, depressed ascending activity to 46±9% of control, but enhanced spinal reflex activity by 73±92%. These results demonstrate that stimulation of 5-HT₃ and methysergide-sensitive 5-HT receptors can inhibit ascending activity and facilitate spinal reflex activity elicited by activation of bladder afferents. It is suggested that descending serotonergic pathways may participate in the spinal coordination of urinary continence.     

Sympathetic rhythms in spinal cats

Simultaneous recordings from preganglionic sympathetic nerves at different spinal levels, cervical sympathetic and greater splanchnic, reveal the presence of common periodicities as shown by cross-correlation and power spectral analysis; the major types of periodicities are cardiac, respiratory and 10/sec rhythm. These common periodicities could be explained in two ways: (1) there are common periodic inputs to the two types of preganglionic neurons; and (2) there are feedback connections in the spinal cord between the two groups of neurons. To distinguish between these two possibilities, spinal cord transections at C2–C3 were performed on decerebrate unanesthetized cats; recordings were then taken at hourly intervals for more than 12 h, during which time activity gradually increased but still remained small compared to pre-section levels. This low level activity showed no sign of periodicity. Asphyxia of sufficient duration produced increased activity in sympathetic nerves. Splanchnic activity during asphyxia had 2–3/sec oscillations; but the cross-correlation histograms (CCHs) of cervical sympathetic and splanchnic activity were almost flat. Strychnine excited spinal cord neurons more effectively than asphyxia; the CCHs showed locking of activity in phrenic, cervical sympathetic and splanchnic nerves on a slow time-scale (1–5 sec), but no appreciable locking of cervical sympathetic and splanchnic activity on a faster time-scale (100–500 msec) such as occurs in the intact animal. Thus, while there can be oscillation of sympathetic activity at the spinal cord level, the normally occurring synchrony of oscillations between different segmental levels is dependent on inputs from the brain stem.     

Classification of dorsal horn neurons based on somatic receptive fields in cats with intact and transected spinal cords: neural plasticity

Classification of dorsal horn neurons based on cell activity responses to somatic receptive fields stimulation, was compared between anesthetized cats with transected or intact cords. Results showed a significant (P≤0.001) difference. In animals with transected cords, dorsal horn neurons responded with less specificity to noxious and innocuous stimulation. The results are consistent with the proposition that loss of supraspinal influences plays a significant role in determining response characteristics of dorsal horn neurons.     

Excitability level-setting mechanisms in the pons: their behavioral support in decerebrate, reflex standing and freely moving, intact cats

In the acute precollicular-postmammillary decerebrate cat, stimulation of the mesencephalic locomotor region (MLR) induces "controlled locomotion" on a moving treadmill. Stimulation of the dorsal area and of the ventral area of the pons at its midline elicited a long-lasting decrease and an increase in the tone of the hindlimb extensor muscles, respectively. By selecting the stimulus strength according to the stimulus site, it was possible to set the extensor muscle tone level, that is the "background excitability" of the brain stem and the spinal cord. Locomotor effects induced by MLR stimulation were greatly modified by the set level of background excitability. When the background excitability was high, MLR stimulation evoked "spastic" locomotor movement, while "atonic" locomotor movement was evoked when it was low. Furthermore, stimulation of the ventral area alone also evoked "spastic" locomotor movement. During locomotion in intact cats, stimulation of the dorsal area evoked a series of postural changes. Within a few seconds from the beginning of stimulation, the cat ceased to walk, but maintained a standing posture with or without a locomotor figure. With continuation of this stimulation, it squatted and then lay down on the floor in a sequential manner. Stimulation of the ventral area of the pons evoked an almost opposite series of postural changes. Within a few seconds from the beginning of stimulation, the cat changed from a lying to a squatting posture, and then stood, started to walk and continued to walk during the period of stimulation. All these results demonstrate that an increase in extensor muscle tone and activation of the spinal stepping generator are not separate phenomena, and suggest that integration of neuronal mechanisms involved in the setting of the background excitability and in locomotor movement is a prerequisite for successful expression of locomotor behavior both in decerebrate and intact cats.     

There is an inverse relationship between the reflex size from wrist flexors and paw preference in spinal cats

The relationship between paw preference and reflex size from wrist flexors was studied in spinal cats. Paw preference was assessed by a food-reaching test. The monsynaptic H reflex and the polysynaptic reflexes were recorded from the median or ulnar nerves following stimulation of the same nerves electrically. The mono- and polysynaptic reflexes were found to be significantly larger on the left side than the right side in right-preferent spinal cats and vice versa in left-preferent spinal cats.     

Excitability of spinal inhibitory circuits in patients with spasticity.

The excitability of Ia inhibition and D1 inhibition after stimulation of the common peroneal nerve to the soleus motoneuron pool was investigated in 37 spastic patients at rest and onset of voluntary ankle dorsiflexion. Ia inhibition was determined as the short-latency depression of the soleus H-reflex and D1 inhibition as the long-latency depression. There was no significant difference in Ia inhibition between the paraplegic and control groups, however Ia inhibition in the hemiplegic group was significantly decreased. D1 inhibition was reduced in the paraplegic and hemiplegic groups compared with controls. Although inhibition of the soleus H-reflex appeared at the onset of voluntary dorsiflexion in control subjects, it was not observed in the patients. Although the excitability of the Ia inhibitory pathway at rest in the patients did not differ from that in control subjects, facilitation of the Ia inhibitory pathway at the onset of movement was decreased in the patients. Ia inhibition and D1 inhibition were evaluated in two paraplegic patients who were treated with local anesthesia and surgery, respectively. The excitability of both inhibitory pathways at rest was unchanged despite improvement of reciprocal movement in one patient, and was enhanced despite reduction in muscle strength in the other patient. The excitability of spinal inhibitory pathways at rest was not always reflected by motor function in spastic patients.