Effects Of Spinal Transection Research Articles

Tail arteries from chronically spinalized rats have potentiated responses to nerve stimulation in vitro

Patients with severe spinal cord lesions that damage descending autonomic pathways generally have low resting arterial pressure but bladder or colon distension or unheeded injuries may elicit a life-threatening hypertensive episode. Such episodes (known as autonomic dysreflexia) are thought to result from the loss of descending baroreflex inhibition and/or plasticity within the spinal cord. However, it is not clear whether changes in the periphery contribute to the exaggerated reflex vasoconstriction. The effects of spinal transection at T7-8 on nerve- and agonist-evoked contractions of the rat tail artery were investigated in vitro. Isometric contractions of arterial segments were recorded and responses of arteries from spinalized animals ('spinalized arteries') and age-matched and sham-operated controls were compared. Two and eight weeks after transection, nerve stimulation at 0.1-10 Hz produced contractions of greater force and duration in spinalized arteries. At both stages, the alpha-adrenoceptor antagonists prazosin (10 nm) and idazoxan (0.1 microm) produced less blockade of nerve-evoked contraction in spinalized arteries. Two weeks after transection, spinalized arteries were supersensitive to the alpha(1)-adrenoceptor agonist phenylephrine, and the alpha(2)-adrenoceptor agonist, clonidine, but 8 weeks after transection, spinalized arteries were supersensitive only to clonidine. Contractions of spinalized arteries elicited by 60 mm K(+) were larger and decayed more slowly at both stages. These findings demonstrate that spinal transection markedly increases nerve-evoked contractions and this can, in part, be accounted for by increased reactivity of the vascular smooth muscle to vasoconstrictor agents. This hyper-reactivity may contribute to the genesis of autonomic dysreflexia in patients.

Effects of sacrocaudal spinal cord transection and transplantation of fetal spinal tissue on withdrawal reflexes of the tail.

Reflex responses to electrocutaneous stimulation of the tail were characterized in awake cats, before and after transection of the spinal cord at sacrocaudal levels S3-Ca1. Consistent with effects of spinal transection at higher levels, postoperative cutaneous reflexes were initially depressed, and the tail was flaccid. Recovery ensued over the course of 70-90 days after sacrocaudal transection. Preoperative and chronic postlesion reflexes elicited by electrocutaneous stimulation were graded in amplitude as a function of stimulus intensity. Chronic postlesion testing of electrocutaneous reflexes revealed greater than normal peak amplitudes, peak latencies, total amplitudes (power), and durations, particularly for higher stimulus intensities. Thus, sacrocaudal transection produced effects representative of the spastic syndrome. In contrast, exaggerated reflex responsivity did not develop for a group of cats that received transplants of fetal spinal cord tissue within sacrocaudal transection cavities at the time of injury, in conjunction with long-term immunosuppression by cyclosporine. We conclude that gray matter replacement and potential neuroprotective actions of the grafts and/or immunosuppression prevent development of the spastic syndrome. This argues that the spastic syndrome does not result entirely from interruption of long spinal pathways.

Activation of Coeruleospinal Noradrenergic Inhibitory Controls during Withdrawal from Morphine in the Rat

We previously reported that withdrawal from morphine induces the expression of Fos, a marker of neuronal activity, in spinal cord neurons, particularly in laminae I and II of the superficial dorsal horn, and that the magnitude of Fos expression is increased in rats with a midthoracic spinal transection. We suggested that loss of withdrawal-associated increases in descending inhibitory controls that arise in the brainstem underlie the increased Fos expression after spinal transection. Here, we addressed the origin of the supraspinal inhibition. We injected rats intracerebroventricularly with saline or anti-dopamine-beta-hydroxylase-saporin, a toxin that destroys noradrenergic neurons of the locus coeruleus. Eleven days later, we implanted rats with morphine or placebo pellets, and after 4 d, we precipitated withdrawal with naltrexone. One hour later, the rats were killed, their brains and spinal cords were removed, and transverse sections of the brains and spinal cords were immunoreacted with an antibody to Fos. In placebo-pelleted rats, the toxin injection did not alter behavior and did not induce expression of the Fos protein. However, compared with saline-injected withdrawing rats, the toxin-treated rats that underwent withdrawal demonstrated an intense withdrawal behavior rarely seen in the absence of toxin, namely forepaw fluttering. The rats also had significantly increased Fos-like immunoreactivity in all laminae of the cervical cord and in laminae I and II and the ventral horn of the lumbar cord. No differences were recorded in the sacral cord. We conclude that the effects of spinal transection in rats that withdraw from morphine in part reflect a loss of coeruleospinal noradrenergic inhibitory controls.

Descending modulation of Fos expression after persistent peripheral inflammation.

The effects of spinal transection on Fos protein expression following complete Freund's adjuvant-induced hindpaw inflammation and hyperalgesia were studied. Fos-like immunoreactivity (LI) was used as a measure of neuronal activity in dorsal horn nociceptive pathways. Induction of Fos-LI in spinally transected rats with 3 days of hindpaw inflammation was significantly increased in ipsilateral lumbar (L 4,5) spinal cord, when compared with control animals with similar inflammation but an intact spinal cord. The contralateral side of spinally transected rats also showed significant induction of Fos-LI compared to the non-inflamed side of control rats. Since Fos induction provides an indication of the level of neuronal activity in response to a given stimulus, these results suggest that the net effect of brain stem descending pathways is to dampen central hyper-excitability in the spinal cord induced by tissue inflammation and hyperalgesia.

Axial muscle EMG responses evoked by cutaneous flank nerves in the female rat: effects of spinal transection, steroid hormones, and anesthesia

In the lateral longissimus muscle (LL) of ovariectomized, female rats anesthetized with low surgical doses of urethane (1.0 g/kg), cutaneous reflexes with similar EMG and response patterns could be elicited from CNS-intact rats and from rats 24 h after complete thoracic spinal cord transection. The probability of eliciting a response to contralateral cutaneous nerve stimulation alone is much lower in rats with complete spinal transections compared to CNS-intact rats. For both CNS-intact and spinal-transected rats, responses to ipsilateral cutaneous nerve stimulation had a shorter latency and required significantly less current on average than responses to contralateral stimulation. The respective currents for eliciting threshold responses to ipsi- and contralateral stimulation are less for CNS-intact than spinal-transected rats. For both CNS-intact and spinal-transected rats, responses to bilateral cutaneous nerve stimulation were inconsistent in the same animal from run to run. With the variability of response at this anesthetic level, no consistent effects of progesterone (acute, i.v.) or estrogen (acute, i.v. and pretreatment, s.c.) were observed in spinal-transected rats. Intravenous progesterone reduced early, unilateral responses in CNS-intact rats anesthetized with 1.0 g of urethane/kg. For both CNS-intact and spinal-transected rats, additional anesthesia during EMG recording produced a gradual decline in response magnitude which could be recovered with a modest increase in stimulus intensity. However, spinal-transected rats appear to require less anesthesia to reduce comparable responses. The results suggest that supraspinal input is especially effective for facilitating contralateral cutaneous reflexes in back muscles, whereas it contributes more equally with afferent input and segmental circuitry to the efficacy of ipsilateral cutaneous reflexes.

Effects of T 2 spinal transection on compensation of horizontal canal related activity in the medial vestibular nucleus following unilateral labyrinth ablation in the decerebrate gerbil

The effects of spinal transection at T 2 upon static and dynamic responses of type I and II neurons in the medial vestibular nucleus after vestibular compensation were investigated in decerebrate Mongolian gerbils ( Meriones unguiculatus). Spinal transection in compensated animals resulted in bilaterally depressed spontaneous activity and asymmetry in the response gain of type I neurons, suggesting that tonic spinal inputs contribute to vestibular compensation through effects upon type I neurons.

The role of tail skin temperature in the facilitation of the tail‐flick reflex after spinal transection or interference with descending serotonergic neurotransmission

We examined in mice whether tail skin temperatures and tail-flick reflexes were changed after spinal transection or intrathecal (i.th.) injection of the serotonin (5-HT) neurotoxin 5,6-dihydroxytryptamine (5,6-DHT) or the 5-HT receptor antagonist metergoline. Transection of the spinal cord reduced tail-flick latency (the time needed to evoke the tail-flick reflex by radiant heat) and increased tail skin temperature 15-21 days after surgery. Analysis of covariance showed that the effect of tail skin temperature on tail-flick latency was far more pronounced than the effect of spinal transection. Intrathecal injection of 5,6-DHT (5 or 10 micrograms mouse-1), which extensively reduced the spinal levels of 5-HT, reduced tail-flick latency and increased tail skin temperature 1-5 days after treatment. Similarly, tail-flick latency was shortened and tail skin temperature elevated 15 min after i.th. injection of metergoline (0.5 micrograms mouse-1). Analysis of covariance showed no significant effect of i.th. 5,6-DHT or i.th. metergoline on tail-flick latency. Tail skin temperature, on the other hand, had a highly significant effect on tail-flick latency. The results show that the facilitation of the tail-flick reflex in spinally transected mice and mice injected i.th. with 5,6-DHT or metergoline is mainly caused by increased tail skin temperature. The data do not indicate that descending 5-HT pathways tonically inhibit the tail-flick reflex.

Acute effects of spinal transection on EPSPs produced by single homonymous Ia-fibers in soleus α-motoneurons in the cat

Pages 1678-1694: T. C. Cope, K. R. Hickman, and B. R. Botterman, “Acute effects of spinal transection on EPSPs produced by single homonymous Ia-fibers in soleus agr-motoneurons in the cat.” Page 1692, right column, acknowledgments, the following paragraph should be inserted: Present address of T. C. Cope: Dept. of Physiology and Biophysics, Mail Stop 409, Hahnemann University, Broad and Vine Sts., Philadelphia, PA 19102. Page 1684, Fig. 3, should appear as follows: See PDF for Figure

Acute effects of spinal transection on EPSPs produced by single homonymous Ia-fibers in soleus alpha-motoneurons in the cat.

1. Excitatory postsynaptic potentials (EPSPs) generated in soleus motoneurons by single homonymous Ia-fibers were measured using intracellular recording and the spike-triggered averaging technique. Two groups of barbiturate-anesthetized adult cats were studied: one with the spinal cord intact and the other with the spinal cord severed at thoracic segment 13 (T13) several hours prior to recording. 2. In cord-transected cats, single homonymous Ia-fibers produced EPSPs in soleus motoneurons that were, on average, larger and faster rising relative to normal, as they are for those produced in medial gastrocnemius (MG) motoneurons (8, 12, 13, 40). Specifically, mean EPSP amplitude and rise time were, respectively, 261 +/- 22 microV and 0.65 +/- 0.05 ms for the transected group vs. 160 +/- 21 microV and 0.96 +/- 0.08 ms for the intact group. The group means for each parameter were significantly different (P less than 0.005). 3. The group difference in EPSP amplitude was largely due to a decrease in number of small EPSPs in the transected group (11% less than 100 microV compared with the normal 41%) and not due to the occurrence of unusually large ones. Ratios of the largest to smallest amplitude EPSPs produced in the same motoneuron were similarly distributed for intact and transected groups, implying that the effect of transection on EPSP size was uniform across different Ia-fiber synapses made with the same motoneuron. Mean EPSP amplitude for each transected cat (n = 5) was larger than normal, but in some cases the increase took greater than 10 h to express itself. 4. The normal tendency for EPSP rise time to decline on average with amplitude was absent in the transected group, wherein rise time was reduced to similar average values in all amplitude categories. This suggests that the decrease in rise time occurred independently of the increase in amplitude. In contrast, EPSP half-width, which tended tow ward lower than normal values [5.63 +/- 0.36 (SE) ms vs. 6.51 +/- 0.44 ms; P greater than 0.10], decreased in proportion with rise time as evidenced by the preservation of the normal relation between those parameters in transected cats. Normalizing EPSPs by motoneuron time constant (tau) reduced the group differences in rise time and half-width, suggesting that a fall in tau contributes to the abbreviation of EPSP time course. 5. The condition of the spinal cord best accounted for differences in synaptic strength between groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Development of spontaneous motility in the guppy embryo (Lebistes reticulatus) and the effect of spinal transection.

Guppy (Lebistes reticulatus) embryos pass through a distinct sequence of motor behaviors that leads to swimming capability during the course of their development. We have characterized these activities in order of appearance, with several corresponding morphological features, as belonging to the coil stage, tail-twitch stage, S-movement stage, and swimming stage. A primary feature of development was an increase in the amount of activity per unit of time over these four stages. The developmental pattern of motility was not interrupted by spinal transection until the onset of swimming, implying that supraspinal information is not required for the occurrence of the primitive behaviors that precede swimming. Elimination of swimming by spinal transection did not elicit a reversion to less complex activities, suggesting that once the cerebral control for swimming is developed, it represents a hardwired system not behaviorally reducible to antecedent components.

Evidence for two distinct sympathoinhibitory bulbo-spinal systems

Yohimbine hydrochloride (0.5 mg kg , i.v.) caused a long-lasting potentiation of electrodermal (sympathetic-cholinergic) reflexes in intact anaesthetized and decerebrate unanaesthetized cats. Transection of the cervical spinal cord also resulted in an increased amplitude of the sudomotor reflex in unanaesthetized decerebrate preparations. Depletion of monoamines in the CNS by pretreatment with reserpine (5 mg kg , i.p.) and α-methyl- p-tyrosine (2 × 300 mg kg , i.p.) reduced the concentrations of norepinephrine, dopamine and serotonin to less than 93% of control levels in the thoracic spinal cord. In monoamine-depleted preparations, yohimbine no longer facilitated the reflex amplitude whereas the effect of spinal transection was not altered. These results suggest that there are two distinct sympathoinhibitory systems in the lower brain stem that converge on spinal sympathetic neurons, one of which is monoaminergic and one of which is not. Evidence for the baroreceptor-independent nature of these descending inhibitory systems is discussed.

Histopathological reactions an axonal regeneration in the transected spinal cord of Hibernating squirrels.

The failure of axonal regeneration in the transected spinal cord of mammals has been attributed to many factors, including an intrinsic lack of regenerative capacity of mature CNS neurons, mechanical obstruction of axonal elongation by glial-connective tissue scars, necrosis of spinal tissue resulting in cavitation, lack of trophic influences sufficient to sustain outgrowth, and contact inhibition resulting from the formation of aberrant synapses. Assessment of te relative importance of each of these factors requires animal models in which one or more of these pathological processes can be eliminated. We therefore examined the effects of spinal transection in the hibernating animal because, during hibernation, collagen formation is depressed while nerve regeneration and slow axonal transport are maintained. Midthoracic spinal transections were performed in hibernating ground squirrels and the spinal cords were examined histologically 1-6 months later. The lesion site was composed primarily of a loose accumulation of macrophages and showed minimal glial and collagenous scarring, or cavitation. There was extensive regeneration of intrinsic spinal cord and dorsal root fibers. These axons grew to the margin of the lesion where they turned abruptly and continued growing along the interface between the lesion and the spinal cord. We conclude (1) that mammalian spinal-cord neurons have considerable regenerative potential; (2) that such mechanical impediments as collagenous and glial scarring, cyst formation, and cavitation cannot provide the sole explanation of why regeneration in the mammalian CNS is abortive; and (3) that specific physical and chemical properties of the cells in the environment of the growth cone regulate the extent and orientation of regenerative axonal outgrowth.

Effects of spinal transection on presynaptic markers for glutamatergic neurons in the rat.

To evaluate the hypothesis that glutamic acid may be the neurotransmitter of descending, excitatory supraspinal pathways, the uptake and release of L-[3H] glutamate and the levels of endogenous glutamate were measured in preparations from rat lumbar spinal cord following complete mid-thoracic transection. Following transection, the activity of the synaptosomal high-affinity glutamate uptake process was increased in both dorsal and ventral halves of lumbar cord between 1 and 14 days after transection and returned to control levels by 21 days posttransection. At 7 days, the increased activity of the uptake process for L-[3H]glutamate resulted in elevation of Vmax with no significant alteration in KT as compared to age-matched controls. Depolarization-induced release of L-[3H]glutamate from prelabeled slices did not differ significantly from control in the lesioned rat except at 21 days after lesion when the amount of tritium release was significantly greater in the transected preparations than in control. Amino acid analysis of the lumbar cord from control and transected rats indicated only a 10% decrease in the level of endogenous glutamate and no alterations in the concentration of GABA and glycine 7 days after lesion. These findings do not support the hypothesis that glutamate serves as a major excitatory neurotransmitter in supraspinal pathways innervating the lumbar cord of the rat.

Effects of spinal transection in neonatal and weanling rats: Survival of function

The spinal cord of neonatal rats and weanling rats was transected midthoracically. The recovery and maturation of responses in the hind quarters were followed and compared with response development in normal rats. In rats transected as neonates, the hind limbs supported the hind quarters, the tail was dorsiflexed, and the hind limbs stepped during locomotion. When a hind limb fell through a grid, struggling movements, replacement, and a response similar to tactile placing were observed. Rapid extension often bounced the hind quarters off a grid when the foot pads contacted a grid bar. Pinching elicited clonic flexion and wriggling of the hind quarters with a prolonged afterdischarge. In animals transected as weanlings, the hind limbs and tail were passively extended and did not participate in locomotion. The hind limbs also hung passively through a grid and struggling was brief. Clonic flexion and wriggling to pinch lacked an afterdischarge. Choreoathetoidlike movements and spasms were common in the weanling group. In a number of respects including temporal correspondence in the appearance of certain responses, the response maturation of the neonatally transected animal resembled the ontogeny of responses in the normal animal. These data indicate that the local development of the spinal cord continues in the absence of supraspinal control. Hence it appears that the presence or absence of supraspinal control during development is the basis for the differences in the survival of responses from the isolated spinal cords of the neonatal group when compared to the weanling animals. This “survival of function” effect may help to explain the sparing of function often found after lesions in the developing nervous system.

Effect of spinal transection on the metabolism of 5-hydroxyindoles formed in vivo from 3H-tryptophan in the rat spinal cord.

AbstractThe nerve impulse flow in 5‐hydroxytryptamine (5‐HT) neurons descending to the caudal part of the spinal cord of rats was interrupted by a spinal transection. At various time intervals after the operation 3H‐tryptophan was administered i.v. and the accumulations of labelled 5‐HT and 5‐hydroxyindoleacetic acid (5‐HIAA) in the cord were determined. 6–8 days after the section the cord caudal to the lesion was almost depleted of 5‐HT and very little 3H‐5‐HT was formed from the labelled precursor. Between 8 and 24 h post‐lesion the level of 5‐HT was increased by 20 % below the lesion, whereas the accumulation of 3H‐5‐HT was markedly reduced. Immediately after the transection the endogenous 5‐HT level as well as the 3H‐5‐HT accumulation were unchanged in the caudal cord. The accumulation of 3H‐5‐HIAA below the section was reduced at all time intervals after the operation. The specific activity of tryptophan seemed to be increased following nerve section. The results indicate that 5‐HIAA synthesis is controlled by nerve impulse activity. The synthesis of 5‐HT was not directly dependent on neuronal activity or tryptophan levels but seemed to be inversely correlated to the endogenous 5‐HT level.