Injured Cats Research Articles

Characterization of Acute Traumatic Coagulopathy in Cats and Association with Clinicopathological Parameters at Presentation.

This study aimed to document rotational thromboelastometric (ROTEM) characteristics of traumatized cats and to investigate associations between clinicopathological parameters and acute traumatic coagulopathy (ATC). A secondary goal was to determine the relevance of autoheparinization in injured cats. Cats presenting with acute (<12 hours) trauma were eligible. Cats were allocated to the ATC group (≥2 hypocoagulable parameters) or non-ATC group (≤1 hypocoagulable parameter) based on ROTEM analysis. Clinicopathological parameters were compared between groups and regression was used to find variables associated with ATC. Heparinase-modified ROTEM (HepTEM) was used to assess for heparin effects in a subgroup. Fifty-three cats were included, and the incidence of ATC was 15%. Prolongation of both intrinsic and extrinsic clotting times (CT) was the most frequently altered ROTEM variable in the ATC group, but CTInTEM-prolongation also occurred in 47% of non-ATC cats. The incidence of autoheparinization, defined as concurrent CTInTEM prolongation and CTInTEM:HepTEM ratio >1.1, was 41% and was observed in both cats with and without ATC. None of the evaluated clinicopathological parameters were different between groups or associated with ATC. Acute traumatic coagulopathy in cats is mainly characterized by prolonged CT. No relationship between clinicopathological variables and ATC was identified and prediction of ATC based on these variables was not possible. While autoheparinization is important in cats, it is not the sole cause for ATC.

Global Strategies for Population Management of Domestic Cats (Felis catus): A Systematic Review to Inform Best Practice Management for Remote Indigenous Communities in Australia.

Simple SummaryA systematic review process was used to identify the current global cat population management practices for owned, free-roaming cat populations, particularly those suited to remote Indigenous communities in Australia. Based on this review, a combination of three methods is recommended. The first method, Surgical Sterilisation (SS), requires owners to take their socialised cats to a facility for surgical sterilisation and then take them home. The second method, Trap-Neuter-Release (TNR) traps, neuters (sterilises) and returns healthy owned cats, which are unsocialised to the point where trapping is necessary, to their homes, and the third method, Trap-Remove (TR), traps and removes unwanted social cats via adoption and unhealthy cats via euthanasia. Conducting these three methods together over a long-term period appears to be consistent with current global best practice for humane and ethical management of cat populations in these communities.Pet domestic cat (Felis catus) populations are increasing all around the world, resulting in an increase in contact with humans and wildlife, potentially spreading zoonotic diseases and predating on wildlife. With the recently identified rise in cat populations in remote Indigenous communities in Australia, culturally appropriate cat population management strategies are required. A systematic review process was conducted to review the current global cat population management practices that are suitable for owned, free-roaming cat populations in these communities. Eight articles on in-situ field cat populations and five studies simulating computer modelled cat populations reported results of 66 population management interventions. Surgical Sterilisation (SS) was used in all socialised owned cat articles. The trap–neuter–release (TNR) method was used most frequently on unsocialised cats and gained the best results when the trap–remove (TR) method was used concurrently to adopt out unwanted social cats and euthanise ill or injured cats. The results of this review suggest that long-term TNR/SS programs supplemented with TR provide the current most ethically sound best practice, humane method of managing cat populations in remote Australian Indigenous communities. It is also recognised that no one plan will fit all, and that further research on the micro-level techniques used to deploy both TNR and TR needs to occur, and that culturally appropriate community consultation during all processes is vital in achieving a sustainable management program.

Performance evaluation and validation of the Animal Trauma Triage score and modified Glasgow Coma Scale in injured cats: A Veterinary Committee on Trauma registry study.

To examine the Animal Trauma Triage (ATT) and modified Glasgow Coma Scale (mGCS) scores as predictors of mortality in injured cats. Observational cohort study conducted September 2013 to March 2015. Nine Level I and II veterinary trauma centers. Consecutive sample of 711 cats reported on the Veterinary Committee on Trauma (VetCOT) case registry. None. We compared the predictive power (area under receiver operating characteristic curve; AUROC) and calibration of the ATT and mGCS scores to their components. Overall mortality risk was 16.5% (95% confidence interval [CI], 13.9-19.4). Head trauma prevalence was 11.8% (n = 84). The ATT score showed a linear relationship with mortality risk. Discriminatory performance of the ATT score was excellent (AUROC = 0.87 [95% CI, 0.84-0.90]). Each ATT score increase of 1 point was associated with an increase in mortality odds of 1.78 (95% CI, 1.61-1.97, P<0.001). The eye/muscle/integument category of the ATT showed the lowest discrimination (AUROC = 0.60). When this component, skeletal, and cardiac components were omitted from score calculation, there was no loss in discriminatory capacity compared with the full score (AUROC = 0.86 vs 0.87, respectively, P = 0.66). The mGCS showed fair performance overall for prediction of mortality, but the point estimate of performance improved when restricted to head trauma patients (AUROC = 0.75, 95% CI, 0.70-0.80 vs AUROC = 0.80, 95% CI, 0.70-0.90). The motor component of the mGCS showed the best predictive performance (AUROC = 0.71); however, the full score performed better than the motor component alone (P = 0.004). When assessment was restricted to patients with head injury (n = 84), there was no difference in performance between the ATT and mGCS scores (AUROC = 0.82 vs 0.80, P = 0.67). On a large, multicenter dataset of feline trauma patients, the ATT score showed excellent discrimination and calibration for predicting mortality; however, an abbreviated score calculated from the perfusion, respiratory, and neurologic categories showed equivalent performance.

Influence of urothelial or suburothelial cholinergic receptors on bladder reflexes in chronic spinal cord injured cats

The effects of intravesical administration of a muscarinic receptor agonist (oxotremorine-M, OXO-M) and antagonist (atropine methyl nitrate, AMN) and of a nicotinic receptor agonist (nicotine) and antagonist (hexamethonium, C6) on reflex bladder activity were investigated in conscious female chronic spinal cord injured (SCI) cats using cystometry. OXO-M (50μM) decreased bladder capacity (BC) for triggering micturition contractions, increased maximal micturition pressure (MMP), increased frequency and area under the curve of pre-micturition contractions (PMC-AUC). Nicotine (250μM) decreased BC, increased MMP, but did not alter PMC-AUC. The effects of OXO-M on BC and PMC-AUC were suppressed by intravesical administration of AMN (50–100μM), and the effects of nicotine were blocked by hexamethonium (1mM). Antagonists infused intravesically alone did not alter reflex bladder activity. However, AMN (0.2mg/kg, subcutaneously) decreased PMC-AUC. 8-OH-DPAT (0.5mg/kg, s.c.), a 5-HT1A receptor agonist, suppressed the OXO-M-induced decrease in BC but not the enhancement of PMC-AUC. These results indicate that activation of cholinergic receptors located near the lumenal surface of the bladder modulates two types of reflex bladder activity (i.e., micturition and pre-micturition contractions). The effects may be mediated by activation of receptors on suburothelial afferent nerves or receptors on urothelial cells which release transmitters that can in turn alter afferent excitability. The selective action of nicotine on BC, while OXO-M affects both BC and PMC-AUC, suggests that micturition reflexes and PMCs are activated by different populations of afferent nerves. The selective suppression of the OXO-M effect on BC by 8-OH-DPAT without altering the effect on PMCs supports this hypothesis. The failure of intravesical administration of either AMN or hexamethonium alone to alter bladder activity indicates that cholinergic receptors located near the lumenal surface do not tonically regulate bladder reflex mechanisms in the SCI cat.

Tamoxifen Promotes Axonal Preservation and Gait Locomotion Recovery after Spinal Cord Injury in Cats

We performed experiments in cats with a spinal cord penetrating hemisection at T13-L1 level, with and without tamoxifen treatment. The results showed that the numbers of the ipsilateral and contralateral ventral horn neurons were reduced to less than half in the nontreated animals compared with the treated ones. Also, axons myelin sheet was preserved to almost normal values in treated cats. On the contrary, in the untreated animals, their myelin sheet was reduced to 28% at 30 days after injury (DAI), in both the ipsilateral and contralateral regions of the spinal cord. Additionally, we made hindlimb kinematics experiments to study the effects of tamoxifen on cat locomotion after the injury: at 4, 16, and 30 DAI. We observed that the ipsilateral hindlimb angular displacement (AD) of the pendulum-like movements (PLM) during gait locomotion was recovered to almost normal values in treated cats. Contralateral PLM acquired similar values to those obtained in intact cats. At 4 DAI, untreated animals showed a compensatory increment of PLM occurring in the contralateral hindlimb, which was partially recovered at 30 DAI. Our findings indicate that tamoxifen exerts a neuroprotective effect and preserves or produces myelinated axons, which could benefit the locomotion recovery in injured cats.

Nutritional analysis and microbiological evaluation of commercially available enteral diets for cats

To determine the prevalence of nutrients less than or greater than accepted standards in commercially available enteral diets for cats, and to identify contamination incidence in enteral diets for cats. Prospective cross-sectional study. University teaching hospital. Seven commercial enteral diets for cats. Labels were evaluated to determine if diets were intended to be nutritionally complete and balanced. One diet under storage techniques partially representative of clinical conditions was sampled on days 0, 1, 3, 5, and 7 of storage for aerobic bacterial culture. All 7 diets were analyzed for key nutrients and results were compared to Association of American Feed Control Officials (AAFCO) Nutrient Profiles for Adult Cats for maintenance and National Research Council recommended allowance (NRC-RA). From label information, 4 diets were classified as complete and balanced and 3 diets were classified as not complete and balanced. All 7 diets had at least 1 nutrient less than the AAFCO minimums and the NRC-RA. The total number of nutrients less than AAFCO minimums ranged from 3 to 9 (median = 4), with iron, potassium, and manganese being the most common. Concentrations of some nutrients were undetectable. None of the samples tested had a positive aerobic culture at baseline (day 0) or on subsequent samples from days 1, 3, 5, and 7 under any storage condition. None of the diets analyzed met all of the minimum nutrient concentrations. While short-term feeding may not be of concern for an individual patient, clinicians should be aware of potential nutritional limitations when feeding enteral diets to ill or injured cats.

Bladder and Sphincter Control after Spinal Cord Injury

A new neuroprosthesis to restore both continence and micturition was developed in chronic spinal cord injured (SCI) cats based on pudendal nerve stimulation and blockade. The present mini‐review summarizes our progress in the design and development of a new stimulation strategy to implement this new neuroprosthesis. Our studies showed that the pudendal‐to‐bladder spinal reflex could be either excitatory or inhibitory, depending on the frequency of pudendal nerve stimulation. High‐frequency biphasic electrical stimulation can reversibly block pudendal nerve conduction to suppress detrusor sphincter dyssynergia (DSD). By combining the different frequencies of pudendal nerve stimulation, both continence and micturition could be restored in chronic SCI cats, indicating the possibility that a successful clinical application of this new stimulation strategy might be achieved in the near future.

In vivo DTI of the healthy and injured cat spinal cord at high spatial and angular resolution

Spinal cord diffusion tensor imaging (DTI) is challenging in many ways: the small size of the cord, physiological motion and susceptibility artifacts pose daunting obstacles to the acquisition of high-quality data. Here, we present DTI results computed from in vivo studies of the healthy and injured spinal cord of five cats. Both high spatial (1.1 mm3) and angular (55 directions) resolutions were used to optimise modelling of the diffusion process. Also, particular effort was directed towards a strategy that limits susceptibility artifacts. For validation purposes, acquisitions were repeated in two cats before and after making a spinal lesion. As a result, various axonal trajectories were identified by tractography including dorsal and ventral columns as well as lateral tracts. Also, fibre bundles showed robust disruption at the site of spinal cord injuries (partial and complete) via tractography, accompanied with significantly lower fractional anisotropy values at the site of lesions. Important outcomes of this work are (i) tractography-based localisation of anatomical tracts in the thoraco-lumbar spinal cord and (ii) in vivo assessment of axonal integrity following experimental spinal cord injury.

Bladder inhibition or voiding induced by pudendal nerve stimulation in chronic spinal cord injured cats

To investigate pudendal-to-bladder spinal reflexes in chronic spinal cord injured (SCI) cats induced by electrical stimulation of the pudendal nerve. Bladder inhibition or voiding induced by pudendal nerve stimulation at different frequencies (3 or 20 Hz) was studied in three female, chronic SCI cats under alpha-chloralose anesthesia. Voiding induced by a slow infusion (2-4 ml/min) of saline into the bladder was very inefficient (voiding efficiency=7.3%+/-0.9%). Pudendal nerve stimulation at 3 Hz applied during the slow infusion inhibited reflex bladder activity, and significantly increased bladder capacity to 147.2+/-6.1% of its control capacity. When the 3-Hz stimulation was terminated, voiding rapidly occurred and the voiding efficiency was increased to 25.4+/-6.1%, but residual bladder volume was not reduced. Pudendal nerve stimulation at 20 Hz induced large bladder contractions, but failed to induce voiding during the stimulation due to the direct activation of the motor pathway to the external urethral sphincter. However, intermittent pudendal nerve stimulation at 20 Hz induced post-stimulus voiding with 78.3+/-12.1% voiding efficiency. The voiding pressures (39.3+/-6.2 cmH2O) induced by the intermittent pudendal nerve stimulation were higher than the voiding pressures (23.1+/-1.7 cmH2O) induced by bladder distension. The flow rate during post-stimulus voiding induced by the intermittent pudendal nerve stimulation was significantly higher (0.93+/-0.04 ml/sec) than during voiding induced by bladder distension (0.23+/-0.07 ml/sec). This study indicates that a neural prosthetic device based on pudendal nerve stimulation might be developed to restore micturition function for people with SCI.

A comparison of cardiorespiratory variables during isoflurane–fentanyl and propofol–fentanyl anaesthesia for surgery in injured cats

ObjectiveTo compare haemodynamic and respiratory variables during isoflurane–fentanyl (IF) and propofol–fentanyl (PF) anaesthesia for surgery in injured cats. Study designProspective, randomized, controlled clinical study. Animals Thirty-three client-owned injured cats undergoing orthopaedic surgery. Materials and methodsPre-anaesthetic medication was intravenous midazolam 1 mg kg−1, butorphanol 0.4 mg kg−1 and ketamine 2 mg kg−1. Anaesthesia was induced with propofol (P) and maintained with either: (a) a continuous rate infusion (CRI) of fentanyl (F) 0.02 mg kg−1 hour−1 and isoflurane (initial end-tidal concentration of 1%), (b) a fentanyl CRI (dose as before) and sevoflurane (initial end-tidal concentration of 2%) or (c) a CRI of propofol (12 mg kg−1 hour−1). All three techniques were given to effect until surgical anaesthesia was achieved. Heart rate and rhythm (ECG), mean arterial blood pressure, respiratory rate, tidal volume and end-tidal CO2 concentration were recorded. Venous blood gas analysis was performed before and after sedation, and at the end of anaesthesia. Blood chemistry and blood cell counts were assessed before, at the end of, and 24 hours after anaesthesia. The variables recorded from cats anaesthetized with IF and PF were compared. ResultsMean end-expiratory isoflurane concentration was 1.19 ± 0.19%. The propofol infusion rate was 11.4 ± 0.8 mg kg−1 hour−1. No significant differences between the two groups in heart rate were identified; no cardiac dysrhythmias were recorded. Mean arterial blood pressure was significantly lower in IF cats during skin incision (p = 0.01), during surgery without intense surgical stimulation (p < 0.01) and during surgery with intense surgical stimulation (p = 0.01). Nine of 11 cats in the IF group were markedly hypotensive (34–49 mmHg) while seven of 11 cats in group PF were mildly hypotensive (49–59 mmHg). One of 11 cats in group IF and nine of 11 cats in group PF required intermittent positive pressure ventilation (IPPV) to maintain end-tidal CO2 levels below 6.66 kPa (50 mmHg). Conclusion and clinical relevance Despite the necessity to ventilate the lungs of cats in the PF group, arterial blood pressure was better maintained. Propofol–fentanyl anaesthesia is better for surgery in injured cats providing the means to impose IPPV are available.

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 α-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 μA 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.

Neural control of locomotion: sensory control of the central pattern generator and its relation to treadmill training

Many studies have shown that a special treadmill training is effective in restoring locomotor function in cats with a complete spinal lesion. In the last few years it has become possible to regain some locomotor activity in patients suffering from a spinal cord injury through an intense training on a treadmill, as in cats. The ideas behind this approach owe much to insights derived from studies on spinalized animals. The neural system responsible for the locomotor restoration in both cats and humans is thought to be located at spinal level and is referred to as the central pattern generator. The evidence for such a spinal central pattern generator is reviewed in part 1. An important element in the treadmill training for both spinal injured cats and humans is the provision of adequate locomotor related sensory input, which can possibly activate and/or regulate the spinal locomotor circuitry. This part of the review deals with the afferent control of the central pattern generator. Furthermore, the results of treadmill training for both cats and humans and their relation to sensory input are treated. These insights can possibly contribute to the design of a better treadmill training program for the rehabilitation of gait in spinal cord injured patients. Copyright 1998 Elsevier Science B.V. All rights reserved

Lack of effect of postinjury treatment with methylprednisolone or tirilazad mesylate on the increase in eicosanoid levels in the acutely injured cat spinal cord.

Methylprednisolone (MP) improves motor recovery in spinal cord-injured patients when administered in a 24 h intensive high dose regimen beginning within 8 h after spinal cord injury (SCI). The rationale for this regimen has been based upon the need for high doses (i.e., 30 mg/kg initial IV dose) to inhibit posttraumatic lipid peroxidation (LP) in the injured spinal segment. However, injury also triggers the immediate calcium-mediated activation of phospholipase A2 (PLA2), the release of arachidonic acid, and the enzymatic formation of potentially deleterious prostaglandins (PGE2 alpha, PGE2), thromboxane A2 (TXA2), and leukotrienes (LTs). Thus, in view of the glucocorticoid receptor-mediated inhibition of PLA2 that underlies much of MP's antiinflammatory actions, an additional neuroprotective mechanism may relate to an inhibition of eicosanoid formation. Using the cat spinal cord compression model (180g x 5 min at L3; Na pentobarbitol anesthesia), we examined whether 30 min postinjury dosing with MP (30 mg/kg IV) could attenuate spinal tissue eicosanoid levels measured by enzyme immunoassay at 1 h (Experiment 1). Pial blood flow was measured over the dorsal columns at the injury site using laser doppler flowmetry to monitor posttraumatic hyperperfusion as an index of the microvascular pathophysiology of acute SCI. In vehicle treated animals at 1 h postinjury, there was a significant increase in the tissue levels of PGF2 alpha (+290%), PGE2 (+260%), TXB2 (stable analog of TXA2, +126%), and LTB4 (+73%) in comparison to sham, uninjured animals. However, 6-keto-PGF1 alpha (stable analog of prostacyclin or PGI2) and LTC4 did not increase. Methylprednisolone did not reduce the increase in eicosanoid production. In the case of LTB4 and LTC4, MP actually increased the levels further. In addition, we examined the effects of a double dose MP regimen (30 mg/kg IV at 30 min plus 15 mg/kg IV at 2.5 h postinjury) on spinal cord eicosanoid levels at 4 h postinjury (Experiment 2). At 4 h postinjury, significant increases in PGF2 alpha, PGE2, TXB2, and 6-keto-PGF1 alpha were observed, and with the exception of PGE2, no MP attenuation of the increased eicosanoids was seen. These results fail to provide evidence that postinjury administration of high dose MP exerts a significant anti-PLA2 action. On the other hand, MP effectively inhibited secondary spinal cord pial hyperperfusion, which is believed to be largely mediated by free radical-lipid peroxidative mechanisms. Thus, it seems likely that the protective action of MP on the acute microvascular pathophysiology of SCI is mediated by its well-documented effects on posttraumatic LP.(ABSTRACT TRUNCATED AT 400 WORDS)

Electrical Field Distribution Within the Injured Cat Spinal Cord: Injury Potentials and Field Distribution

This study investigated the spontaneous injury potentials measured after contusion or transection injury to the cat spinal cord. In addition, the distribution of electrical field potentials on the surface and within the spinal cord were measured following applied electrical fields after transection and contusion injuries. After transection of the spinal cord, the injury potentials were -19.8 +/- 2.6 mV; after contusion of the spinal cord, the injury potentials were -9.5 +/- 2.2 mV. These potentials returned to control values within 2.5-4h after injury. The electrical field distribution measured on the dorsal surface, as well as within the spinal cord, after the application of a 10 microA current, showed little difference between contusion and transection injuries. Scalar potential fields were measured using two configurations of stimulating electrodes: dorsal to dorsal (D-D), in which both electrodes were placed epidurally on the dorsal surface of the spinal cord, and ventral to dorsal (V-D), in which one electrode was placed dorsally and one ventrally. As reported in normal uninjured cats, the total current in the midsagittal plane for the D-D configuration was largely confined to the dorsal portion of the spinal cord; with the V-D configuration, the current distribution was uniform throughout the spinal cord. In the injured spinal cord, the equipotential lines midway between the stimulating electrodes have a wider separation than in the uninjured spinal cord. Because the magnitude of the electrical field E is equal to the current density J multiplied by the resistivity r, this suggests that either the current density is reduced or that the resistivity is reduced.

In vivo angiogenesis by platelet-derived wound-healing formula in injured spinal cord

In vivo angiogenesis was investigated using platelet-derived wound-healing formula (PDWHF) in the injured cat spinal cord. Twentytwo gauge teflon sheaths, which had been coated with PDWHF-Hydron or only with Hydron, were inserted into the spinal cords of cats and the injured cats were maintained for 3 weeks. Selection of PDWHF-Hydron or Hydron was double blinded. The PDWHF-Hydron group showed notable neovascularization as well as dilation around the injury site, and this was statistically significant when compared to the control group. PDWHF seems to play a role in the healing processes of spinal cord injury and may have important interactions with other growth factors and in particular neurogenic growth factor.

Effect of Delayed Administration of U74006F (Tirilazad Mesylate) on Recovery of Locomotor Function After Experimental Spinal Cord Injury

Beginning at either 30 minutes, 2 hours, 4 hours, or 8 hours after 180 g compression of the cat L2 spinal cord for 5 minutes, infusion of U74006F was initiated. In this series, the cats received a total U74006F dose of 5 mg/kg/48 hours. An additional group of injured cats was treated at 8 hours postinjury with a three-fold higher dose of U74006F (i.e., a total 48-hour dose of 15 mg/kg). Controls received an equal volume of vehicle (citrate-buffered saline) delivered over 48 hours. The cats were evaluated weekly for 4 weeks for recovery of overground locomotion based on an 11-point scale by an investigator blinded to the time and type (i.e., vehicle or drug) of material administered. By 4 weeks postinjury, there was no significant difference in the locomotor recovery of cats that received U74006F at either 30 minutes, 2 hours, 4 hours, or 8 hours after injury. However, only recovery in the groups treated at 30 minutes, 2 hours, or 4 hours after injury was significantly greater than vehicle-treated controls. Locomotor function in cats receiving either 5 mg/kg/48 hours or 15 mg/kg/48 hours of U74006F at 8 hours postinjury was not significantly different from that of the vehicle-treated animals. Mean (+/- SEM) 4-week recovery scores were 6.8 +/- 0.9, 5.9 +/- 1.0, 7.2 +/- 1.1, and 4.7 +/- 2.9 out of 11 for cats treated at 30 minutes, 2 hours, 4 hours, or 8 hours postinjury, respectively, with the 5 mg/kg/48 hour dose. The mean recovery score for cats treated at 8 hours after injury with the 15 mg/kg/48 hour dose was 3.4 +/- 1.8. The average score for the vehicle-treated controls was 1.8 +/- 0.8. These findings demonstrate that U74006F can significantly protect locomotor function in our model of compression spinal cord injury if administered as late as 4 hours postinjury. Delaying administration of the compound to 8 hours after injury results in considerable loss of its protective capabilities even if the dose is increased threefold.

Central axons in injured cat spinal cord recover electrophysiological function following remyelination by Schwann cells

Axonal morphometry of the lesion site was studied at 3 months after standardized weight-drop contusion injury of the thoracic spinal cord in adult cats. From a sample of 25 injured animals, 12 examples were found in which all surviving axons in the dorsal column were remyelinated by Schwann cells, at the level of the lesion. The dorsolateral tracts were also peripherally myelinated in 6 of these cases, and there was no central myelination in complete transverse sections through the lesion in four animals. In these cases, Schwann cell myelination was prevalent for several millimeters on either side of the lesion center. The extent of Schwann cell invasion correlated with the intensity of injury, measured by overall axon loss. Cortical somatosensory evoked potentials (CSEP) were recorded from all animals before and at intervals for 12 weeks after injury. CSEP to hindlimb (tibial nerve) stimulation were lost immediately at injury but some recovery took place during the first month. The extent of CSEP recovery correlated negatively but weakly with overall axon loss. Clear SEP were recorded at 3 months post-injury in 3 of the animals in which the dorsal columns were remyelinated by Schwann cells; in one of these, the dorsolateral funiculi were also peripherally myelinated. In another, oligodendrocyte myelination was absent from the entire transverse section of the lesion site. Thus, abnormal remyelination by cells of the peripheral nervous system, which is known to occur in a variety of central demyelinating conditions, is capable of restoring effective action potential conduction in mammalian spinal cord sensory tracts.

Comparison of vestibular and auditory startle responses in the rat and cat

Cats, humans, and many other animals show stereotyped EMG responses in limb and axial muscles if suddenly dropped into free-fall. In cats, these free-fall responses (FFR) consist of highly synchronized bursts in most limb and axial muscles at 18–22 ms. We have used FFR to evaluate descending motor function and recovery in chronic spinal injured cats. Here FFR are compared with auditory evoked startle reflexes (ASR) in the hindlimb muscles of the rat and cat to determine whether they are related, and whether they could be used to evaluate descending motor function in the rat. ASR and FFR in the two species were similar except that the earliest components for both responses occurred around 9 ms in the rat versus 18–20 ms in the cat. Also, FFR in cats were usually more consistent and greater in amplitude during repeated drops than in rats, while the converse was true for ASR. Rat FFR amplitudes increased significantly after administering ketamine or 4-aminopyridine (4-AP), especially with both drugs together, while ASR amplitudes did not. FFR in cats recorded under ketamine analgesia were not normally improved by 4-AP. Finally, both FFR and ASR were suppressed by pentobarbital, chloralose, or motor activity. These data suggest that: (1) FFR appears to be a vestibular evoked startle reflex; (2) in the rat, ASR should be useful as a test of descending motor function following spinal injury, and (3) the combination of ketamine and 4-AP may be useful in revealing the presence of functional spinal pathways after CNS trauma.

Effects of guanabenz on bladder function after spinal cord injury

AbstractThe effect of guanabenz, an alpha‐2 adrenoceptor agonist, on urinary bladder function and neurological recovery was studied in cats subjected to a 400 gm‐cm contusion injury of the thoracic spinal cord. Eight cats were treated with 1.3 mg/kg of guanabenz three hours after injury and then twice daily for eight weeks. Four injured cats were used as controls (untreated), and 12 intact cats were used as normal controls. Cystometrograms were used to measure bladder function in all the animals studied.Guanabenz given intraperitoneally significantly improved urinary bladder function and neurological recovery. It appears that treatment of spinal cats with guanabenz has an ameliorative effect on functional reorganization of the central spinal pathways modulating spasticity, micturition, and lower limb function.

Regeneration of cat corneal endothelium induced in vivo by fibroblast growth factor

The corneal endothelium of man, primates and carnivores has limited regenerative ability. Fibroblast growth factor (FGF) stimulates the proliferation of various mesoderm-derived cells, including corneal endothelial cells, in vitro. In the present work the effect of FGF on the regeneration of injured cat endothelium in vivo was studied. Scraping of cat corneal endothelium off Descemet's membrane was carried out by a specially designed instrument. FGF from crude preparations (25 micrograms in 50 microliter saline) or affinity purified FGF (0.5 micrograms in 25 microliter saline) were injected immediately after the scraping of the endothelium, and in both cases significant stimulation of endothelium regeneration was observed. During the first 2 weeks after scraping, the endothelial cell density (ECD) in FGF-treated eyes was higher by a factor of 1.7-2.3 than that in the control eyes. This marked difference decreased with time, but even after 12 weeks the ECD in FGF-treated eyes was higher by a factor of 1.15-1.30 than in the control eyes. Furthermore, FGF improved the polygonal shape of the cells and decreased the corneal thickness. These results clearly demonstrate the efficacy of FGF in inducing the proliferation of cat corneal endothelial cells in vivo and indicate its potential application in clinical practice.