Cutaneus Trunci Muscle Research Articles

Evolutionary comparative analysis of the extrinsic thoracic limb muscles in three procyonids (Procyon cancrivorus Cuvier, 1798, Nasua nasua Linnaeus, 1766, andPotos flavus Schreber, 1774) based on their attachments and innervation.

The procyonids (Procyon cancrivorus, Nasua nasua and Potos flavus) are Neotropical carnivorans with the ability to climb trees; however, each one has different locomotor preferences. Thereby, P. flavus is highly arboreal, P. cancrivorus is mainly terrestrial with abilities to swim, and N. nasua is also fossorial. These activities not only require movements of the hands but stabilize the thoracic limb, an action performed by the extrinsic muscles. Besides, former descriptions performed in procyonid species have obsolete terms for these muscles, generating confusion about the comparison among species. Thereby, muscle innervation has also been used to support the evolutionary derivation of the muscles. Therefore, this study aimed to describe the attachments and innervations of these muscles in three procyonids. There were intra- and interspecific anatomical variations in the attachments of all extrinsic thoracic limb muscles. However, based on the innervation, several evolutionary derivations in procyonids could be found, such as: the cleidobrachialis muscle derived from the deltoideus muscle; the atlantoscapularis muscle of P. flavus derived from the serratus ventralis cervicis muscle; the pectoralis transversus muscle derived from the pectoralis profundus and superficiales muscles; and the pectoralis abdominalis muscle derived from the cutaneus trunci muscle. Some functions could be associated with locomotor habits, among them a highly developed pectoralis abdominalis in Nasua for its fossorial habits and the atlantoscapularis in Potos for its arboreal and prehensile habits. Thus, the extrinsic muscles in procyonids have evolved for locomotor preferences, but mainly due to their phylogenetic relationship within the family Procyonidae.

Central Plasticity of Cutaneous Afferents Is Associated with Nociceptive Hyperreflexia after Spinal Cord Injury in Rats.

Electrical stimulations of dorsal cutaneous nerves (DCNs) at each lumbothoracic spinal level produce the bilateral cutaneus trunci muscle (CTM) reflex responses which consist of two temporal components: an early and late responses purportedly mediated by Aδ and C fibers, respectively. We have previously reported central projections of DCN A and C fibers and demonstrated that different projection patterns of those afferent types contributed to the somatotopic organization of CTM reflex responses. Unilateral hemisection spinal cord injury (SCI) was made at T10 spinal segments to investigate the plasticity of early and late CTM responses 6 weeks after injury. Both early and late responses were drastically increased in response to both ipsi- and contralateral DCN stimulations both above (T6 and T8) and below (T12 and L1) the levels of injury demonstrating that nociceptive hyperreflexia developed at 6 weeks following hemisection SCI. We also found that DCN A and C fibers centrally sprouted, expanded their projection areas, and increased synaptic terminations in both T7 and T13, which correlated with the size of hemisection injury. These data demonstrate that central sprouting of cutaneous afferents away from the site of injury is closely associated with enhanced responses of intraspinal signal processing potentially contributing to nociceptive hyperreflexia following SCI.

Temporal and spatial dynamics of spinal sensorimotor processing in an intersegmental cutaneous nociceptive reflex.

The cutaneus trunci muscle (CTM) reflex produces a skin "shrug" in response to pinch on a rat's back through a three-part neural circuit: 1) A-fiber and C-fiber afferents in segmental dorsal cutaneous nerves (DCNs) from lumbar to cervical levels, 2) ascending propriospinal interneurons, and 3) the CTM motoneuron pool located at the cervicothoracic junction. We recorded neurograms from a CTM nerve branch in response to electrical stimulation. The pulse trains were delivered at multiple DCNs (T6-L1), on both sides of the midline, at two stimulus strengths (0.5 or 5 mA, to activate Aδ fibers or Aδ and C fibers, respectively) and four stimulation frequencies (1, 2, 5, or 10 Hz) for 20 s. We quantified both the temporal dynamics (i.e., latency, sensitization, habituation, and frequency dependence) and the spatial dynamics (spinal level) of the reflex. The evoked responses were time-windowed into Early, Mid, Late, and Ongoing phases, of which the Mid phase, between the Early (Aδ fiber mediated) and Late (C fiber mediated) phases, has not been previously identified. All phases of the response varied with stimulus strength, frequency, history, and DCN level/side stimulated. In addition, we observed nociceptive characteristics like C fiber-mediated sensitization (wind-up) and habituation. Finally, the range of latencies in the ipsilateral responses were not very large rostrocaudally, suggesting a myelinated neural path within the ipsilateral spinal cord for at least the A fiber-mediated Early-phase response. Overall, these results demonstrate that the CTM reflex shares the temporal dynamics in other nociceptive reflexes and exhibits spatial (segmental and lateral) dynamics not seen in those reflexes.NEW & NOTEWORTHY We have physiologically studied an intersegmental reflex exploring detailed temporal, stimulus strength-based, stimulation history-dependent, lateral and segmental quantification of the reflex responses to cutaneous nociceptive stimulations. We found several physiological features in this reflex pathway, e.g., wind-up, latency changes, and somatotopic differences. These physiological observations allow us to understand how the anatomy of this reflex may be organized. We have also identified a new phase of this reflex, termed the "mid" response.

Peripheral and central anatomical organization of cutaneous afferent subtypes in a rat nociceptive intersegmental spinal reflex.

Stimulation of rat segmental dorsal cutaneous nerves (DCNs) evokes the nociceptive intersegmental cutaneus trunci muscle (CTM) reflex. The reflex consists of early and late responses, mediated by Aδ and C fibers, respectively, based on required stimulation strengths, and shows segmental differences in terms of amplitude and duration. We have now investigated whether the peripheral or central anatomy of nociceptive afferent subtypes in different DCNs also vary in a segmental manner. The numbers of different axon subtypes, determined by axon diameter, were analyzed across peripheral DCNs from T6 to L1. The central projections of T7 and T13 DCN afferents were traced using DCN injections of cholera toxin subunit B (CTB) for myelinated A fibers and isolectin B4 (IB4) for unmyelinated C fibers and both labels were quantified in the dorsal horns. Peripheral axon subtype numbers did not differ significantly across DCNs. Centrally, IB4+ , but not CTB+ , projection areas were different between T7 and T13, consistent with different segmental CTM neurogram responses. At both levels, A fibers projected to deeper layers of the dorsal horn than did C fibers. These termination sites are consistent with both mono- and polysynaptic connections between these afferents and the ascending propriospinal interneurons of the reflex. Also analyzed were the spatial distribution, the synaptic termination, and the glutamatergic transporter profiles of DCN A and C fibers and their relationship to calcitonin gene-related peptide (CGRP) staining in the dorsal horn.

Effects of methylprednisolone and 4-chloro-3-hydroxyanthranilic acid in experimental spinal cord injury in the guinea pig appear to be mediated by different and potentially complementary mechanisms.

Blinded, placebo-controlled, parallel treatment group studies of the effects of methylprednisolone (MP) or 4-chloro-3-hydroxyanthranilate (4-Cl-3-HAA) on behavioral outcome and quinolinic acid tissue levels from experimental thoracic spinal cord injury in adult guinea pigs. To compare the effects of treatment with high-dose MP, a corticosteroid, and 4-Cl-3-HAA, a compound that inhibits synthesis of the neurotoxin quinolinic acid (QUIN) by activated macrophages. To explore the effect of different times of treatment using these two approaches to ameliorating secondary tissue damage. Laboratory animal studies at the University of North Carolina, Chapel Hill, NC, USA. Standardized spinal cord injuries were produced in anesthetized guinea pigs, using lateral compression of the spinal cord. Behavioral impairment and recovery were measured by placing and toe-spread responses (motor function), cutaneus trunci muscle reflex receptive field areas and somatosensory-evoked potentials (sensory function). Tissue quinolinic acid levels were measured by gas chromatograph/mass spectrometry. The current experiments showed a reduction in delayed loss of motor and sensory function in the guinea pig with MP (150 mg kg(-1), intraperitoneally in split doses between 0.5 and 6 h), but no significant reduction in tissue QUIN. Improved sensory function was seen with a single dose of 60 mg kg(-1) MP intraperitoneally at 5 h after injury, but not at 10 h after injury. A single dose of 4-Cl-3-HAA at 5 h in the guinea pig did not produce the sensory and motor improvements seen in previous studies with 12 days of dosing, beginning at 5 h. These studies, together with earlier findings, indicate that both drugs can attenuate secondary pathologic damage after SCI, but through separate mechanisms. These are most likely an acute reduction by MP of oxidative processes and reduction by 4-Cl-3-HAA of QUIN synthesis.

Localization of the cutaneus trunci muscle reflex in horses

To determine the magnitude and location of skin movement attributable to the cutaneus trunci muscle reflex in response to localized stimulation of the skin of the dorsolateral aspect of the thoracic wall in horses. 8 horses. A grid of 56 reflective markers was applied to the lateral aspect of the body wall of each horse; markers were placed at 10-cm intervals in 7 rows and 8 columns. A motion analysis system with 10 infrared cameras was used to track movements of the markers in response to tactile stimulation of the dorsolateral aspect of the thoracic wall at the levels of T6, T11, and T16. Marker movement data determined after skin stimulation were used to create a skin deformation gradient tensor field, which was analyzed with custom software. The sites of maximal skin deformation were located close to the stimulation sites; the centers of the twitch responses were located a mean distance of 7.7 to 12.8 cm ventral and between 6.6 cm cranial and 3.1 cm caudal to the stimulation sites. Findings of this study may have implications for assessment of nerve conduction velocities of the cutaneus trunci muscle reflex and may enhance understanding of the responses of horses to placement of tack or other equipment on skin over the cutaneus trunci muscles.

Contractile and morphological properties of hamster retractor muscle following 16 h of cold preservation

IntroductionCold hypoxia is a common factor in cold tissue preservation and mammalian hibernation. The purpose of this study was to determine the effects of cold preservation on the function of the retractor (RET) muscle of the hamster in the non-hibernating state and compare these with previously published data (van der Heijden et al., 2000) [52] on the rat cutaneus trunci (CT) muscle. Materials and methodsAfter cold storage (16h at 4°C), muscles were stimulated electrically to measure maximum tetanus tension (P0) and histologically analyzed. The protective effects of addition of the antioxidants trolox and deferiprone and the calcium release inhibitor BDM to the storage fluid were determined. ResultsAfter storage, the twitch threshold current was increased (from 60 to 500μA) and P0 was decreased to 27% of control. RET morphology remained unaffected. RET muscle function was protected by trolox and deferiprone (P0, resp., 43% and 59% of control). Addition of BDM had no effect on the RET. ConclusionsThe observed effects of cold preservation and of trolox and deferiprone on the RET were comparable to those on CT muscle function, as reported in a previously published study (van der Heijden et al., 2000) [52]. Both hamster RET and rat CT muscles show considerable functional damage due to actions of reactive oxygen species. In contrast to the CT, in the RET cold preservation-induced functional injury could not be prevented by BDM and was not accompanied by morphological damage such as necrosis and edema. This suggests that the RET myocytes possess a specific adaptation to withstand the Ca2+ overload induced by cold ischemia.

4-Chloro-3-Hydroxyanthranilate Reduces Local Quinolinic Acid Synthesis, Improves Functional Recovery, and Preserves White Matter after Spinal Cord Injury

Inflammatory processes within the central nervous system (CNS) contribute significantly to the pathogenesis of a broad range of neurologic diseases, including spinal cord injury (SCI). One mechanism by which immune activation causes neurologic symptoms and tissue injury is via the production of neurotoxins by activated macrophages and microglia. In the present study, the role of the endogenous tryptophan metabolite and neurotoxin quinolinic acid (QUIN) in secondary pathology following traumatic SCI was investigated. Adult Hartley guinea pigs were injured by lateral compression of the spinal cord at the 12th thoracic segment (T12). QUIN had accumulated at the site of injury on day 12 post-injury in proportion to the severity of functional neurologic deficits (as assessed by the cutaneus trunci muscle reflex and motor function score at 5 h post-injury). Systemic administration of the 3-hydroxyanthranilate-3,4-dioxygenase (3-HAD) inhibitor, 4-chloro-3-hydroxyanthranilate (4Cl-3HAA; approximately 100 mg/kg every 12 h, beginning 5 h after injury) attenuated local QUIN production and reduced QUIN accumulation at the site of injury by approximately 50% at day 12, without enhanced accumulations of the neuroprotective metabolite kynurenic acid (KYNA). The severity of secondary functional deficits was also reduced by 4Cl-3HAA. In toluidine blue-stained spinal cord sections, the area of surviving intact white matter at the injury site was increased by approximately 100% in the 4Cl-3HAA-treated group. Sparing of both axons and myelin contributed to this increase. These results support the conclusion that QUIN accumulations at the site of injury contribute to secondary functional deficits and tissue damage following SCI.

Reduction of Postincisional Allodynia by Subcutaneous Bupivacaine

An incision of hairy skin of the rat's back provides a new model for postincisional pain to determine the importance of cutaneous anesthesia. Male Sprague-Dawley rats were anesthetized with sevoflurane and given a 0.6-ml subcutaneous injection of bupivacaine (0.25%) under the incision site or the medial lumbar dorsum or at the nuchal midline, 30 min before a 1.0-cm skin incision. Mechanical stimuli (von Frey hairs, 18-250 mN) were applied to measure nociception, indicated by twitching of local subcutaneous muscles, the cutaneus trunci muscle reflex. A graded response score, averaging the twitches weighted by their vigor, or a population response score, measuring the fraction of rats that showed any response, was assessed for 3 days before and over 7 days after incision. von Frey hairs were applied 0.5 cm from the incision to test primary hyperalgesia and 2.0 cm contralateral to the incision for secondary hyperalgesia. Incision induced responses to stimuli that had no effect on intact skin (allodynia) and also enhanced responses to forces that normally gave less than the full reflex (hyperalgesia). Hyperalgesia was present 30 min after surgery, peaked at 3-6 h, and persisted through the week; allodynia had a similar onset but was briefer. Both changes were transiently reversed by subcutaneous morphine (2.5 mg/kg intraperitoneal). Subcutaneous bupivacaine (0.25%), injected preoperatively at the incision site and anesthetizing skin for 2-3 h, suppressed primary allodynia for 1 week but had no effect on hyperalgesia. Secondary allodynia was obliterated, and secondary hyperalgesia attenuated by this treatment. Bupivacaine injected subcutaneously at the nuchal midline before surgery was also effective in abbreviating primary and secondary allodynia, with no signs of sedation, ataxia, or preconvulsive behavior. Incision of rat hairy skin changes pain responses, similar to pain in humans. Preincisional subcutaneous bupivacaine selectively suppresses and shortens allodynia for times far outlasting its local anesthesia, an effect largely from systemic actions.

Behavioral recovery from spinal cord injury following delayed application of polyethylene glycol.

Topical application of the hydrophilic polymer polyethylene glycol (PEG) to isolated adult guinea pig spinal cord injuries has been shown to lead to the recovery of both the anatomical integrity of the tissue and the conduction of nerve impulses through the lesion. Furthermore, a brief (2 min) application of the fusogen (M(r) 1800, 50 % w/v aqueous solution) to the exposed spinal cord injury in vivo can also cause rapid recovery of nerve impulse conduction through the lesion in association with functional recovery. Behavioral recovery was demonstrated using a long-tract, spinal-cord-dependent behavior in rodents known as the cutaneus trunci muscle (CTM) reflex. This reflex is observed as a contraction of the skin of the back in response to tactile stimulation. Here, we confirm and extend these preliminary observations. A severe compression/contusion injury to the exposed thoracic spinal cord of the guinea pig was performed between thoracic vertebrae 10 and 11. Approximately 7 h later, a topical application of PEG was made to the injury (dura removed) for 2 min in 15 experimental animals, and levels of recovery were compared with those of 13 vehicle-treated control animals. In PEG-treated animals, 93 % recovered variable levels of CTM functioning and all recovered some level of conduction through the lesion, as measured by evoked potential techniques. The recovered reflex was relatively normal compared with the quantitative characteristics of the reflex prior to injury with respect to the direction, distance and velocity of skin contraction. Only 23 % of the control population showed any spontaneous CTM recovery (P=0.0003) and none recovered conduction through the lesion during the 1 month period of observation (P=0.0001). These results suggest that repair of nerve membranes by polymeric sealing can provide a novel means for the rapid restoration of function following spinal cord injury.

Effect of calcium chloride marination on bovine Cutaneus trunci muscle

The aim of this investigation was to determine the possibility of using calcium chloride solution in tough muscles ( Cutaneus trunci) to reduce the aging period required to increase tenderness, without introducing undesirable flavors. Muscles were marinated in 0.25 M CaCl 2 solution for 2 h and after that aged for 0, 1, 2, 3, 4, 5 and 7 days. Tenderness was evaluated by the myofibrillar fragmentation index (MFI), Warner Bratzler shear force (WBS) and sensory panel evaluation. MFI values showed significant differences between treated and control samples aged for 1, 2 and 3 days ( P<0.05). MFI values of treated samples aged 3 days were similar to those obtained for the control samples but aged seven days. WBS values were not significantly different between samples. Consumer panelists preferred treated samples aged 3 days to the control ones aged 7 days. It was concluded that calcium chloride treatment can be used in Cutaneus trunci muscle to reduce the aging time required to increase tenderness.

Influence of genotype on contractile protein differentiation in different bovine muscles during foetal life

The purpose of this work was to compare muscle fibre differentiation in two genetic types: Charolais and double-muscled (DM) INRA 95 cattles displaying muscle hypertrophy. Six muscles with different contractile and metabolic characteristics in adult animal: Masseter, Diaphragma (Di), Biceps femoris (BF), Longissimus thoracis, Semitendinosus and Cutaneus trunci (CT) were excised from 60 to 260-day-old foetuses of both genotypes. These muscles present different degrees of hypertrophy in DM animals. Fibre types were characterised by immunohistochemistry using mon- oclonal antibodies raised against different myosin heavy chain isoforms. They were also studied by SDS-PAGE electrophoresis, immunoblotting and ELISA methods. In both genotypes, foetal muscle development involved at least two generations of fibres but their contractile differentiation was more or less delayed in double-muscled animals according to the muscle type. CT muscle, the most hyper- trophied in adults DM, showed the most important differences in the appearance of the primary and secondary fibres in DM foetuses. It showed a delay of differentiation which was made up during the last third of foetal life. Other muscles did not differ in the speed of appearance of the two gener- ations of fibres. They were originated from a higher proliferation of secondary fibres. Moreover, all DM muscles presented similar characteristics at 210 days of foetal life. These characteristics seem to be genetically determined. Just before birth, muscles of double-muscled foetuses were composed of a greater proportion of fast type II fibres than normal animals. The most important differences between genotypes were observed in BF and Di muscles. muscle / foetus / differentiation / cattle / double-muscled

Retroambiguus projections to the cutaneus trunci motoneurons may form a pathway in the central control of mating.

Our laboratory has proposed that the nucleus retroambiguus (NRA) generates the specific motor performance displayed by female cats during mating and that it uses direct pathways to the motoneurons of the lower limb muscles involved in this activity. In the hamster a similar NRA-projection system could generate the typical female mating posture, which is characterized by lordosis of the back as well as elevation of the tail. The present study attempted to determine whether this elevation of the tail is also part of the NRA-mating control system. The basic assumption was that elevation of the tail is a function of the cutaneous trunci muscle (CTM), which was verified by bilateral tetanic stimulation of the lateral thoracic nerves innervating the CTM. It resulted in upward movement of the tail to a position similar to the tail-up position during the lordosis posture. Retrograde tracing results showed that CTM motoneurons are located in the ventral and ventrolateral part of the C(7)-C(8) ventral horn, those innervating the tail region ventrolateral to those innervating the axillary region. Anterograde tracing studies showed that NRA fibers terminate bilaterally in both parts of the CTM motoneuronal cell groups. Electron microscopical studies revealed that labeled NRA terminals make monosynaptic contacts with retrogradely labeled dendrites of CTM motoneurons. Almost all of these terminal profiles had asymmetric synapses and contained spherical vesicles, which suggests an excitatory function. The observation that 15% of the labeled NRA terminals make more than one synaptic contact with a retrogradely labeled CTM motoneuronal dendrite within the same section indicates how powerful the NRA-CTM projection is. The results indicate that during mating the NRA not only could generate the lordosis posture but also the elevation of the tail.

Improving the preservation of isolated rat skeletal muscles stored for 16 hours at 4 degrees C.

Limiting factors for long-term cold preservation of isolated skeletal muscles are increased intracellular calcium levels, the occurrence of hypercontraction, and the overproduction of oxygen free radicals. In the present study, we investigated whether muscle preservation during cold storage could be improved by additives that can protect against such processes or by oxygen supply. The soleus (SOL) and a strip of the cutaneus trunci muscle (CT) from the rat were isolated and stored for 16 hr at 4 degrees C in Bretschneider's Histidine Tryptophane Ketoglutarate (HTK) and subsequently acclimatized in Krebs-Henseleit solution for 90 min at room temperature. The protective effects of 2,3-butanedione monoxime (BDM; reduces intracellular calcium release and inhibits fiber contraction) and of the following antioxidants were investigated: N-tert-butyl-alpha-phenylnitrone (PBN), trolox, desferal, and deferione. The antioxidants and BDM were added to both HTK and Krebs-Henseleit solution. Dose-response curves were made for each of the additives (n> or =4 for each dose). To evaluate the effect of oxygen supply, HTK was aerated with 95% O2/5% CO2. Muscle function (P0), energy metabolism (ATP), and cytoarchitecture were analyzed. The measured values were compared with those of fresh unstored muscles (% of control) and with those of muscles stored in HTK without any additive (multivariate analysis of variance, P<0.05). We found a significant protection of the contractile function (P0) of both muscles after the addition of 1 mM of trolox (SOL: 46% of control; CT: 53%) and after the addition of 3 mM or 0.3 mM of deferione to the SOL and CT, respectively (P0 for both muscles: 55%), whereas no protection was found with PBN (0.03-1 mM) and Desferal (0.001-1 mM). The addition of BDM (10 or 30 mM) resulted in the highest increase of P0 (84% and 60% for the SOL and CT, respectively). The combinations BDM-trolox and BDM-deferione did not further improve the preservation of the SOL function, but P0 values (88% and 91% of control, respectively) were not different from those found for control muscles. Oxygenation of HTK was only beneficial for the SOL (P0: 83%). The improved preservation of muscle function was accompanied by a reduction of the twitch threshold current, increased by storage, suggesting a protective effect of the intervention on the preservation of the muscle cell membrane integrity. Biochemical and histological data corresponded well with the functional data. The results showed that the addition of BDM and antioxidants (trolox and deferione) to the bathing solutions improved the preservation of the function, metabolism, and cytoarchitecture of isolated skeletal muscles after cold storage for 16 hr.

A model for the assessment of sensory recovery of experimental skin grafts.

The return of sensation to skin grafts is often suboptimal. Although the reinnervation of skin grafts has been examined by a number of authors during the past century, studies in humans have left a number of unanswered issues, whereas animal studies have been largely confined to histological work and a few electrophysiological studies. Based on knowledge that rats exhibit a reflexive flick of the back skin in response to stimulation, the authors hypothesized that it should be possible to develop a noninvasive model for assessing return of sensation in experimental skin grafts. Full-thickness skin grafts were created, one per animal, on the dorsa of male Sprague-Dawley rats. Sensory testing was performed using a hand-held pinprick device designed to deliver a stimulus of reproducible force. A positive response was observed as a flick of the dorsal skin--a very reliable reflex involving the cutaneus trunci muscle. The stimulus was delivered to each of 25 sectors of the graft on days 9, 13, 16, 20, 40, 60, and 110 postoperatively. Results were analyzed regarding the percentage of grafts responding at each time point as well as the topographical pattern of sensory return. Evidence of sensation was first detected at day 13 at the margins of the skin grafts and then progressed centrally until homogenous reinnervation (94% of the graft surface) was observed at day 40 and was maintained through the end of the study. Growth Associated Protein (GAP)-43 immunostaining was used to document reinnervation of the skin grafts histologically.

Delayed application of direct current electric fields in experimental spinal cord injuries.

The cutaneus trunci muscle (CTM) reflex of guinea pigs depends on an ascending afferent pathway within the ventrolateral funiculus of the thoracic spinal cord. The expression of this reflex is a phasic contraction of back skin in response to tactile stimulation, which is permanently eliminated by transection of the ventrolateral funiculus. It was shown previously that when a polarized (rostrally negative), weak (300-400 μV/mm) DC electric field is placed across a lateral hemisection of the spinal cord in adult guinea pigs at the time of injury, approximately 13% recover the reflex, while sham-treated animals remain unchanged. In this study, a similar approach was used, except that three months were allowed to pass between the time of hemisection and experimental treatment. No recovery of the CTM reflex was observed in 13 animals with rostrally negative fields, 8 of which were followed for at least 9 months, 5 for 3 months; or in 11 animals with caudally negative applied fields, 8 of which were followed for 9 months and 3 for 3 months.

Morphometric analysis of a model of spinal cord injury in guinea pigs, with behavioral evidence of delayed secondary pathology

A model of spinal cord trauma in guinea pigs is described, based on the concept of compression to a set thickness, as an alternative to compression or contusion with a set force or displacement. The model is technically simple and reliable and circumvents some of the biomechanical problems of contusion techniques. It was designed initially to produce moderate injuries, allowing significant recovery of function. A pair of forceps was modified to form an instrument to compress the spinal cord laterally, over a 5-mm length, to a thickness of 1.2 mm. Such compression injuries of the lower thoracic cord were produced in 12 anesthetized, adult guinea pigs, and the outcome monitored, using successive behavioral tests and morphometry of the lesion at 2–3 months. Chronic histopathology was examined quantitatively with line-sampling of axons in 1-μm plastic sections through the lesion center, stained with toluidine blue. The type and distribution of damage to axons was similar to that seen following weight-drop contusion trauma in cats. Spinal cord function was examined by means of hindlimb reflex testing and motor behavior, vestibulospinal reflex testing, and mapping the receptive field of the cutaneus trunci muscle (CTM) reflex. These injuries characteristically resulted in a delayed onset of functional deficits at 1–2 days after injury, followed by partial recovery over the course of several weeks. Overall, functional outcome correlated significantly with the number of surviving axons in the lesion. The phenomenon of “secondary” pathology was striking at the behavioral level, whereas evidence of delayed injury has been indirect in most animal models. The onset of this secondary process occurred with a longer delay than has been assumed or implied by most suggested mechanisms of secondary pathology. The time course of secondary loss and recovery may be related to that of the inflammatory response at the injury site, particularly the phagocytic activity of macrophages.

The Effects of 4-Aminopyridine on Neurological Deficits in Chronic Cases of Traumatic Spinal Cord Injury in Dogs: A Phase I Clinical Trial

A Phase I trial of 4-aminopyridine (4-AP) was carried out in 39 dogs referred to the veterinary teaching hospital with naturally occurring traumatic paraplegia or paraparesis. The rationale for the study was provided by the observation that 4-AP restores conduction in demyelinated nerve fibers in experimental spinal cord injury. Most injuries (77%) resulted from degenerative disk disease, occurring at or near the thoracolumbar junction, and producing chronic, complete paraplegia. Neurological examination of each dog was recorded on videotape before and at intervals after administration of 4-AP. The drug was administered systemically in total doses between 0.5 and 1 mg/kg body weight. Three areas of neurological status changed significantly at 15-45 minutes following administration of 4-AP: (a) striking improvements in hindlimb placing occurred in 18 animals; (b) increased awareness of painful stimuli to the hindlimb in 10 animals; (c) partial recovery of the cutaneus trunci muscle reflex of the back skin in 9 animals. These effects reversed within a few hours of administration. Other animals (36%) showed no change in neurological signs except a slight enhancement of hindlimb reflex tone. Significant side effects were seen in 6 dogs receiving higher intravenous doses, with elevation of body temperature and apparent anxiety, leading to mild seizures in 3 of the animals. These seizures were controlled with diazepam. The results indicate that conduction block may contribute significantly to functional deficits in closed-cord injuries and that potassium channel blockade may prove to be a valid, if limited approach to therapeutic intervention in chronic paraplegia and paraparesis.

Cutaneus trunci muscle reflex of the guinea pig

The cutaneus trunci muscle reflex in guinea pigs was studied with a combination of video analysis, electromyography, lesioning, and light microscopy. The muscle forms a bilateral, subdermal sheet over much of the trunk. Local contractions of the dorsal part of the muscle are produced in response to brief tactile or electrical stimulation of the skin and consist of a twitch centered 1-2 cm rostral of the stimulus site. The reflex receptive field covers most of the thoracic and lumbar dorsal surface. The sensory information is carried via segmental dorsal cutaneous nerves. Receptive fields of adjacent nerves overlap and form rectangular areas perpendicular to the midline, at thoracic levels. Motor innervation projects through the lateral thoracic nerves of the brachial plexus. The motoneurons are located near the cervical thoracic junction (C7-T1). Lesions of the lower thoracic cord indicate that ascending sensory information is carried to the motor nuclei via the ventral half of the lateral funiculus. This pathway conveys information primarily from ipsilateral skin. There is a weaker input from contralateral skin, crossing at segmental levels. Electromyographic responses to brief electrical stimulation of lower thoracic skin occur usually as 10-12 msec bursts at latencies of 10-20 msec, and do not readily habituate or fatigue at stimulus frequencies below 10 Hz. The reflex persists under light pentobarbital anesthesia. This combination of characteristics makes the reflex useful for a variety of physiological and pathophysiological studies.

Functional recovery after spinal cord hemisection in guinea pigs: The effects of applied electric fields

Right lateral hemisection of the lower thoracic spinal cord was performed in 216 adult guinea pigs. Animals that proved suitable for the study were divided into one control and two experimental groups. Experimental animals were implanted with intraperitoneal stimulators delivering regulated current of 35 or 50 microA through electrodes placed 1 cm rostral and caudal of the hemisection. The cathode was cranial to the lesion in one group (n = 67) and caudal in the other (n = 33). Control animals (n = 62) were implanted with sham stimulators and electrodes delivering no current. The functional status of the animals was measured by tactile stimulation of the back skin to elicit the cutaneus trunci muscle reflex, and by the vestibulospinal free-fall response. The cutaneous response ipsilateral and caudal to the lesion was lost following hemisection and did not recover in any of the control animals or in animals with cathode caudal to the lesion. Recovery of the response was found in 9 of 67 animals in the cathode rostral group, between 56 and 139 days after injury. Toe spreading recovered spontaneously in 80-90% of animals in all groups. Of the possible mechanisms of skin reflex recovery, most current evidence points to regrowth of ascending nerve fibers in the lateral funiculus of the spinal cord local to the lesion.