Whisker-related circuitry in the trigeminal nucleus principalis: Topographic precision.

Single whiskers are topographically represented in the trigeminal (V) nucleus principalis (PrV) by a set of cylindrical aggregates of primary afferent terminals and somata (barrelettes). This isomorphic pattern is transmitted to the thalamus and barrel cortex. However, it is not known if terminals in PrV from neighboring whiskers interdigitate so as to violate rules of spatial parcellation predicted by barrelette borders; nor is it known the extent to which higher order inputs are topographic. The existence of inter-whisker arbor overlap or diffuse higher order inputs would demand additional theoretical principles to account for single whisker dominance in PrV cell responses. In adult rats, first, primary afferent pairs responding to the same or neighboring whiskers and injected with Neurobiotin or horseradish peroxidase were rendered brown or black to color-code their terminal boutons. When collaterals from both fibers appeared in the same topographic plane through PrV, the percentage of the summed area of the two arbor envelopes that overlapped was computed. For same-whisker pairs, overlap was 5 ± 6% (mean ± SD). For within-row neighbors, overlap was 2 ± 5%. For between-row neighbors, overlap was 1 ± 4%. Second, the areas of whisker primary afferent arbors and their corresponding barrelettes in the PrV were compared. In the transverse plane, arbor envelopes significantly exceeded the areas of cytochrome oxidase-stained barrelettes; arbors often extended into neighboring barrelettes. Third, bulk tracing of the projections from the spinal V subnucleus interpolaris (SpVi) to the PrV revealed strict topography such that they connect same-whisker barrelettes in the SpVi and PrV. Thus, whisker primary afferents do not exclusively project to their corresponding PrV barrelette, whereas higher order SpVi inputs to the PrV are precisely topographic.

Changes in electrical perceptual threshold in the first 6 months following spinal cord injury.

OBJECTIVES: To investigate the use of electrical perceptual threshold (EPT) testing to follow the natural history of sensory progression after complete and incomplete acute spinal cord injury (SCI) and to compare EPT changes with the American Spinal Injuries Association (ASIA) Impairment Scale (AIS). STUDY DESIGN: Prospective descriptive study. METHODS: ASIA examination and EPT testing was performed on 17 patients (7 AIS A, 10 AIS B-D), within 1, 3, and 6 months after acute SCI. EPT assessment was carried out bilaterally at ASIA sensory points from 2 levels above the neurological level to all levels below, including the sacral segments. Comparisons of EPT values above, at, and below the SCI were made at the three time points as well as comparisons of EPT data to ASIA assessment. RESULTS: There was poor agreement between lowest normal level on EPT and ASIA assessment. Over time, EPTs tended to deteriorate above and at the ASIA level in AIS A patients with modest changes below the neurological level of injury (NLI), mainly where EPTs correlated with the zone of partial preservation. Sacral sparing was detected in one patient with EPT testing, but not with ASIA assessment. AIS B-D patients showed improvement at the ASIA level and extensive changes, both improvement and deterioration, below the NLI. CONCLUSION: EPT testing has sufficient sensitivity to detect subclinical changes in sensory function as early as the first month post-SCI, which is not apparent in ASIA examination. In particular, the testing is able to show abnormalities at and around the injury site for both complete and incomplete SCI. In addition, EPT allows for the detection and monitoring of alterations, both improvements and deterioration, in the abnormal range of sensation.

Delayed olfactory ensheathing cell transplants reduce nociception after dorsal root injury.

Injury to cervical dorsal roots mimics the deafferentation component of brachial plexus injury in humans, with intractable neuropathic pain in the deafferented limb being a common consequence. Such lesions are generally not amenable to surgical repair. The use of olfactory ensheathing cells (OECs) for dorsal root repair, via acute transplantation, has been successful in several studies. From a clinical point of view, delayed transplantation of OECs would provide a more realistic timeframe for repair. In this study we investigated the effect of delayed OEC transplantation on functional recovery of skilled forepaw movements and amelioration of neuropathic pain, using a C7 and C8 dorsal root injury rat model previously established in our lab. We found that OEC transplantation to the dorsal horn 1 week after root injury effectively attenuated neuropathic disturbances associated with dorsal root injury, including spontaneous pain behavior, tactile allodynia and thermal hyperalgesia. The sensory controls of complex, goal-oriented skilled reaching and ladder walking, however, were not improved by delayed OEC transplantation. We did not detect any significant influence of transplanted OECs on injury-induced central reorganisation and afferent sprouting. The anti-nociceptive effect mediated by OEC transplants may therefore be explained by alternative mechanisms such as modification of inflammation and astrogliosis. The significant effect of OEC transplants in mitigating neuropathic pain may be clinically useful in intractable pain syndromes arising from deafferentation. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia and their prospect for nervous system repair.

Age, gender, and side differences of cutaneous electrical perceptual threshold testing in an able-bodied population.

OBJECTIVE: To investigate age, gender, and left-right differences in cutaneous electrical perceptual threshold (EPT) testing in an able-bodied, Australian sample. STUDY DESIGN: Prospective experimental. SETTING: Hospital-based spinal cord injuries unit. METHODS: Cutaneous electrical stimulation of the 28 dermatomes at ASIA sensory key points (C2-S4/S5) was performed on 29 female and 16 male healthy volunteers aged 21 to 76 years. Mean EPTs for each dermatome were compared (repeated measures ANOVA) for left-right, gender-related, and age-related (50 years of age) differences. RESULTS: There was no group difference between sides (repeated measures ANOVA, P = 0.934). Women across all ages had lower group mean EPTs than men (P < 0.0001). Women younger than age 50 years had lower mean EPTs than those older than age 50 years (P = 0.008). There was no group difference between younger and older men (P = 0.371). Analysis of individual dermatomes revealed no significant differences in thoracic dermatomes between genders or age groups, contrary to the limb dermatomes. CONCLUSION: There were gender differences in EPT values across all ages. Women had higher EPTs as they advanced in age, but this was less clear in men. There was considerable somatotopic variability in EPTs, especially in the lower limbs. If EPT testing is to be applied to detect subclinical changes within a dermatome, establishment of age- and gender-specific somatotopic normograms is a prerequisite.

Selected changes in spinal cord morphology after T4 transection and olfactory ensheathing cell transplantation.

Spinal cord transection at T4 results in severe damage of the nervous tissue, with impairment of motor, sensory and autonomic functions. Transplantation of olfactory ensheathing cells (OECs) has the potential to improve these functions through a number of mechanisms, which include facilitation of regeneration and neuroprotection. For cardiovascular functions, we have previously shown that OECs reduce the duration of autonomic dysreflexia, without evidence of regeneration. To further understand the mechanisms underpinning this improvement, we have studied changes in selected morphological features (cavitation, non-cavity tissue loss, morphology of sympathetic preganglionic neurons and primary afferent fibre density) in the T4-transected rat spinal cord over 9 weeks, both in control and OEC-transplanted animals. T4 transection led to a number of structural changes: gradual formation of cavities, non-cavity tissue loss, a long-term increase in soma size of sympathetic preganglionic neurons and a temporary increase in the extent of their dendritic arbours, and an increase in the density of primary afferent fibres caudal to the lesion. OECs decreased the cavitation and normalised soma size of the sympathetic preganglionic neurons below the lesion, while increasing the extent of dendritic arbours in the preganglionic neurons above the lesion. Thus the OECs may contribute to the normalisation of the dysreflexic hypertension through tissue preservation and normalisation of the morphology of the preganglionic neurons caudal to the lesion, while enhancing the input on the rostral preganglionic neurons, whose vasomotor control remains intact. We hypothesise that these changes are mediated through secretion of soluble trophic factors by the transplanted OECs.

Effects of human OEC-derived cell transplants in rodent spinal cord contusion injury.

Numerous reports indicate that rodent olfactory ensheathing cells (OECs) assist in spinal cord repair and clinical trials have been undertaken using autologous transplantation of human olfactory ensheathing cells (hOECs) as a treatment for spinal cord injury. However, there are few studies investigating the efficacy of hOECs in animal models of spinal cord injury. In this study hOECs were derived from biopsies of human olfactory mucosa, purified by culture in a serum-free medium containing neurotrophin-3, genetically labelled with EGFP, and stored frozen. These hOEC-derived cells were thawed and transplanted into the spinal cord injury site 7 days after a moderate contusion injury of the spinal cord at thoracic level T10 in the athymic rat. Six weeks later the animals receiving the hOEC-derived transplants had greater functional improvement in their hindlimbs than controls, assessed using open field (BBB scale) and horizontal rung walking tests. Histological analysis demonstrated beneficial effects of hOEC-derived cell transplantation: reductions in the volume of the lesion and the cavities within the lesion. The transplanted cells were located at the periphery of the lesion where they integrated with GFAP-positive astrocytes resulting in a significant reduction of GFAP staining intensity adjacent to the lesion. Although their mechanism of action is unclear we conclude that hOEC-derived cell transplants improved functional recovery after transplantation into the contused spinal cord, probably by modulating inflammatory responses and reducing secondary damage to the cord.

Olfactory ensheathing cells reduce duration of autonomic dysreflexia in rats with high spinal cord injury.

Autonomic dysreflexia is a common complication in high spinal cord injury and can result in serious consequences and death. Here we have examined the effect of acute transplantation of olfactory ensheathing cells on cardiovascular functions in rats. After T4 transection, radio-telemetric recording in conscious animals was used to study blood pressure and heart rate at rest and during autonomic dysreflexia for up to 8 weeks post-injury. Olfactory ensheathing cells from syngeneic rats were transplanted at the injury site; control animals received culture medium only. At the study end point, we examined morphometric features of sympathetic preganglionic neurons above and below the injury. T4 transection resulted in a fall in resting mean arterial pressure and an increase in resting heart rate. Colorectal distension, used to trigger autonomic dysreflexia, caused episodic hypertension and bradycardia. Although the cell transplantation had no effect on resting cardiovascular parameters, it led to a significantly faster recovery from hypertension, with the recovery time shortened by approximately 25%. The transection resulted in an increase in soma size of sympathetic preganglionic neurons above and below the injury. OEC transplantation normalised this change below the injury and increased dendritic length of preganglionic neurons above the injury, compared to controls. It has been proposed that changes in sympathetic preganglionic neurons following spinal cord transection may be related to the development of autonomic dysreflexia. Our results suggest that olfactory ensheathing cells may alter the morphology of these neurons, and hence modify their activity in the neuronal networks responsible for the dysreflexic reaction.

Electrical perceptual threshold testing: a validation study.

BACKGROUND/OBJECTIVE: To investigate inter-rater and intra-rater reliability of electrical perceptual threshold (EPT) testing in assessing somatosensory function in healthy volunteers. STUDY DESIGN: Prospective experimental. SETTING: Hospital-based spinal cord injuries unit. METHODS: Cutaneous electrical stimulation of 4 dermatomes at ASIA sensory key points (C3, T1, L3, and S2) was performed on 40 control subjects. The lowest ascending stimulus intensity at which sensation was perceived was recorded as the EPT. Mean EPT values for each dermatome, as determined by 2 testers at 2 time points, were examined and plotted against a normative template. Differences and associations between intra- and inter-rater measurements and left-right measurements were studied. EPT results for 2 people with spinal cord injuries were also examined. RESULTS: EPT measurements from left and right sides, obtained from the 2 time points and 2 testers, were found to be strongly associated, with the exception of left and right side measurements at the S2 dermatome. No significant differences in the mean EPT for tester or time period were found. The intra- and inter-rater reliability was good for all dermatomes tested. Mean EPT measurements fell within the range of a normative template at each of the 4 dermatomes tested. CONCLUSION: EPT is an objective, reproducible, and quantifiable method of assessing sensation in a control group. However, caution should be applied in certain dermatomes such as S2, where there was large variation between left and right side measurements.

Effect of treadmill training on autonomic dysreflexia in spinal cord--injured rats.

BACKGROUND: Weight-supported treadmill training is an emerging rehabilitation method used to improve locomotor ability in patients with spinal cord injury (SCI). However, little research has been undertaken to test the effect of such training on other consequences of SCI, such as neuropathic pain and autonomic dysfunction. OBJECTIVE: This study investigates the effects of chronic treadmill training on the development of autonomic dysreflexia (AD), a form of cardiovascular dysfunction common in patients with cervical or high thoracic injury. METHODS: Treadmill training commenced in adult male rats (n = 11) 3 days following complete T4 transection, whereas a sedentary SCI group (n = 9) and an intact group (n = 6) had no intervention. Treadmill training (up to 0.4 m/s) lasted for 10 min/d 5 days a week, for 6 weeks. Weekly measurements of locomotor ability (BBB scale), baseline mean arterial pressure, and heart rate were made, as were cardiovascular responses to training and colorectal distension (to trigger AD). RESULTS: Treadmill training improved BBB scores from 2 weeks post-transection onward (P = .010). However, it increased AD, resulting in augmented pressor responses from 2 to 6 weeks post-transection (P = .029). Comparison of the vascular response to phenylephrine under ganglionic blockade showed an enhanced vasoconstrictor response in the renal vasculature of trained SCI animals. Immunohistochemical comparison of the L1-L6 spinal cord segments showed an increased area of CGRP immunoreactivity in the dorsal horn (lamina III/IV) of treadmill-trained SCI compared with intact and sedentary SCI animals. CONCLUSIONS: These results suggest that treadmill training exaggerated AD responses perhaps through a combination of enhanced vascular reactivity and central plasticity.

Local response to cold in rat tail after spinal cord transection.

Subjects with severe chronic spinal cord injury (SCI) are prone to hypothermia when they are exposed to relatively low environmental temperatures that are normally well tolerated by healthy individuals. This impaired thermoregulation is presumably due to disconnection of territories below the SCI from supraspinal thermoregulatory centers. However, it is not known how these territories respond to low temperatures. Using a complete transection at T(11) in rats, we examined the responses of the tail to cold (6-9 degrees C) by measuring changes in tail blood flow and skin temperature weekly for 8 wk after SCI. Despite no significant change in baseline mean flow or temperature in the tail, the transection effectively removed the sympathetically mediated supraspinal control of the tail vasculature, since the amplitude of the pulse flow was markedly increased and the natural variations of the mean flow were almost abolished. As expected, the cold challenge before SCI caused a marked drop in mean flow, pulse amplitude, and temperature of the tail. Surprisingly, the drops in mean blood flow and temperature were observed after SCI, although the decrease in flow was slower and the pulse amplitude was not reduced. The results suggest that the cutaneous vasculature of the tail is sensitive to cold and will constrict, despite disconnection from supraspinal centers. This local effect is slow but may be sufficient to maintain some level of thermoregulation to cold. Without this vascular reaction, the effects of SCI on temperature regulation to cold would probably be much worse.

Characterization of rat forepaw function in two models of cervical dorsal root injury.

Dorsal root injury (DRI) disrupts afferent input from the periphery and often leads to sensory deficits and neuropathic pain. Despite cervical root injuries in rodents being a useful model for deafferentation studies, a quantitative characterization of the sensory deficits produced by DRI is still lacking. This study aimed to characterize the different functional deficits resulting from a dorsal two- or four-root (C7-C8 and C5-C8, respectively) crush injury in rats at levels that innervate the forepaws. The impairment of the affected forepaw was assessed by mechanical and thermal pain responses, and rating the performance on the skilled reaching and ladder rung walking tests (LRWT). Postoperatively, only the two-root DRI rats developed mechanical allodynia, which persisted throughout the course of the study. Thermal hyperalgesia peaked at weeks 1 and 6. The four-root DRI animals were less sensitive to mechanical and thermal stimulation. Performance on the skilled reaching task could only be measured in two-root DRI rats, as animals with four-root injury were unable to grasp the pellets at all. On the LRWT, gait impairment was proportional to the severity of the lesion, with four-root DRI animals showing a significantly higher rate of errors than two-root DRI animals. These results suggest that two-root DRI represents a good model to assess treatments for allodynia-induced neuropathic pain, and for the restoration of the sensory component of the skilled motor performance. On the other hand, the four-root DRI would be a useful model when forepaw deafferentation is required.

Correlations between hand preference and cortical thickness in the secondary somatosensory (SII) cortex of the common marmoset, Callithrix jacchus.

Cortical asymmetries are well established in humans for language and motor regions and correlate with handedness. Here the authors investigate structural differences in the hemispheres of left- and right-handed common marmosets using surface photography and histology. The hand preferences of 11 marmosets were assessed over their adult life span using a simple reaching task. A significant correlation was found between the length of the right lateral sulcus/brain weight and the % right-hand preference (r = .86, p = .001). Cortical thickness on the superior bank of the right lateral sulcus posteriorly was also positively correlated with % right-hand preference (r = .69, p = .025). Comparison of this site with previously published functional maps of the marmoset cortex show this area corresponds to SII, a region involved in tactile processing and somatosensory discriminations. It is suggested that the correlation between SII thickness and right-hand preference would be consistent with the fact that right-handed marmosets are more proactive than left-handers in exploring novel objects by touch. Enlargement of a cortical area involved tactile discriminations could be a precursor to the evolution of right-handedness as a population bias.

Crash characteristics of older pedestrian fatalities: dementia pathology may be related to 'at risk' traffic situations.

Older people are over represented among pedestrian casualties, and cognitive decline is an often cited possible contributory factor. Cognitive decline and dementia are intimately associated, however the role dementia might play in older pedestrian crashes has received little attention. This study describes crash characteristics for 52 fatally injured older pedestrians in the Sydney metropolitan area. It investigates the relationship between the extent of neurofibrillary tangles (NFT), a hallmark of Alzheimer's disease in the brain, and particular crash situations. The results demonstrate crash characteristics that are similar to that reported in other studies of older pedestrians. Furthermore, the results suggest that cognitive decline associated with dementia related neuropathology may be associated with specific crash situations. Compared to older pedestrians with no, or low NFT, those with moderate to high NFT were more likely to be: at least partially responsible for the incident; injured while in low complexity situations; involved in impacts with reversing vehicles; impacted in near lanes of traffic; and struck by a vehicle off road. While described as trends only (p<0.2), these findings highlight areas of concern for older pedestrians and suggest potential targets for engineering and behaviour-based countermeasures aimed at reducing casualty numbers among older pedestrians.

Augmented locomotor recovery after spinal cord injury in the athymic nude rat.

The immune response contributes to ongoing secondary tissue destruction following spinal cord injury (SCI). Although infiltrating neutrophils and monocytes have been well studied in this process, T-cells have received less attention. The objective of this study was to assess locomotor recovery and tissue morphology after SCI in athymic (nude) rats, in which T-cell numbers are reduced. Results in athymic rats were compared with heterozygote littermates with normal T-cell profiles and with Sprague-Dawley rats from previous studies in our lab. Following transection of rat spinal cords at T10, we assessed the animals' locomotor recovery on a weekly basis for up to 11 weeks, using the Basso-Beattie-Bresnahan locomotor rating scale. Nude rats showed better locomotor recovery than did heterozygote or Sprague-Dawley rats, achieving scores of 5.6 +/- 0.8 versus 1.0 +/- 0.0, respectively (p = 0.002), at 4 weeks postinjury. The improved recovery of nude rats persisted for the 11-week postinjury assessment period, and was consistent with improved spinal reflexes rather than with recovery of descending motor pathways. Anatomical evaluation at 11 weeks indicated no difference in nude versus heterozygote rats in the size or distribution of cavities caudal to the transection site, but secondary damage was more severe rostral to the transection site in heterozygote rats. In neither group did cavities extend beyond 4 mm caudal to the transection site, and were therefore not directly responsible for the functional differences between the two groups. Cellular expression of the microglia/macrophage antigen ectodysplasin A (ED1) was reduced in nude rats as compared to heterozygotes, but no difference was observed in expression levels of 5-hydroxytryptamine, the 200-kDa neurofilament, or glial fibrillary acidic protein. The findings of the study show that a reduction in T-cell numbers significantly improves locomotor recovery after spinal cord transection, indicating a deleterious role for these immune cells in neural repair after trauma.

Whisker maps in marsupials: nerve lesions and critical periods.

In the wallaby, whisker-related patterns develop over a protracted period of postnatal maturation in the pouch. Afferents arrive simultaneously in the thalamus and cortex from postnatal day (P) 15. Whisker-related patterns are first seen in the thalamus at P50 and are well formed by P73, before cortical patterns first appear (P75) or are well developed (P85). This study used the slow developmental sequence and accessibility of the pouch young to investigate the effect of nerve lesions before afferent arrival, or at times when thalamic patterns are obvious but cortical patterns not yet formed. The left infraorbital nerve supplying the whiskers was cut at P0-93 and animals were perfused at P112-123. Sections through the thalamus (horizontal plane) and cortex (tangential) were reacted for cytochrome oxidase to visualize whisker-related patterns. Lesions of the nerve at P2-5, before innervation of the thalamus or cortex, resulted in an absence of patterns at both levels. Lesions from P66-77 also disrupted thalamic and cortical patterns, despite the fact that thalamic patterns are normally well established by P73. Lesions from P82-93 resulted in normal thalamic and cortical patterns. Thus, despite the wallaby having clearly separated times for the development of patterns at different levels of the pathway, these results suggest a single critical period for the thalamus and cortex, coincident with the maturation of the cortical pattern. Possible mechanisms underpinning this critical period could include dependence of the thalamic pattern on corticothalamic activity or peripheral signals to allow consolidation of thalamic barreloids.

Expression of cardiovascular and behavioural components of conditioned fear to context in T4 spinally transected rats.

A spinal cord transection at the fourth thoracic level (T4) results in paraplegia. It also removes supraspinal control of sympathetic outflow to most viscera and their blood vessels but spares the heart. We studied the effects of such a transection on the expression of the conditioned fear response to context, which includes freezing, 22 kHz ultrasonic vocalisations, a marked pressor response and a slowly rising tachycardia. Rats implanted with radiotelemetric probes were fear conditioned, tested, then transected at T4 and finally re-tested 4 weeks after transection. Baseline blood pressure in transected animals was the same as in intact animals but baseline heart rate was 127 bpm higher. There were clear signs of fear in the transected animals: although freezing occurred in the upper part of the body only, there was a 3 fold increase in the number of ultrasonic vocalisations, most probably due to paralysis of abdominal muscles that made expirations shorter and therefore more frequent. The pressor response of fear was initially the same as in intact animals but controls revealed that this was due to handling during transfer to the aversive context. The rest of the pressor response was markedly reduced (70%) confirming that it depends in large part on a sympathetically mediated increase in vascular resistance in the lower part of the body. The cardiac response was characterized by an initial bradycardia followed by a marked tachycardia, which is consistent with a baroreceptor-mediated reflex response to the altered pressor changes. Finally, none of these changes was observed when the same experiment was repeated in sham transected animals. Thus, the pressor response of fear is in large part mediated by the thoracic cord below T4 and the baroreflex is not inhibited but maintained during conditioned fear.

Spinal cord tissue affects ensheathing cell proliferation and apoptosis.

This study investigates proliferation and apoptosis of olfactory ensheathing cells in cocultures with spinal cord tissue. Proliferation of ensheathing cells was significantly increased when cocultured with explants from uninjured spinal cord, and spinal cord that had been subjected to chronic contusion or chronic needle stab injury, but not to acute needle stab injury. Proliferation rate was highest in cocultures with chronically stabbed cord tissue. Contaminating (p75NGFR-negative) cells in the cultures showed a significantly higher proliferation rate than ensheathing cells. Apoptosis of ensheathing cells was significantly increased in cocultures with acutely stabbed spinal cord explants compared with chronically contused spinal cord explants. These results suggest that delaying transplantation after spinal cord injury may be beneficial to ensheathing cell survival.

Axonal injury in children after motor vehicle crashes: extent, distribution, and size of axonal swellings using beta-APP immunohistochemistry.

The brains of 32 children (3 months to 16 years) who died as a result of motor vehicle collisions were examined for axonal injury using beta-APP immunohistochemistry. The extent and distribution of axonal injury was assessed and quantified throughout the forebrain, brainstem and cerebellum. The mean diameter of immunoreactive axons in the corpus callosum was measured for this pediatric group and, for comparison, a small adult sample. beta-APP immunoreactivity was seen in 14 pediatric cases (survival 35 mins to 87 h), most frequently in the parasagittal white matter (12/14), the corpus callosum (11/14), the brainstem (10/14) and cerebellum (9/14). In 2 cases, axon swelling was visualized in the internal capsule after only 35-45-min survival, earlier than has previously been reported. No immunoreactivity was seen in the remaining 18 cases who died within 1 h. The extent and distribution of axonal injury throughout the brain showed a rapid early increase with increasing survival time and then a slower progression. The diameter of individual callosal axons increased with increasing survival times, rapidly over the first 24 h and then more slowly. There was no statistical difference (p < 0.05) for callosal axon diameters at different survival times between the children and the adults sampled here. The extent and distribution of axonal injury throughout the brain appears to be similar in children to that previously reported in adults. The spatial and temporal spread of axonal damage suggests there may be therapeutic potential for the process to be arrested or slowed in its early stages.

Effects of different anesthetics on the paired-pulse depression of the h reflex in adult rat.

Hyperreflexia is a common feature of spinal cord injury (SCI), and changes in reflex excitability have been reported to be useful in assessing treatments in animal models of cord damage. However, spinal reflexes are known to be dependent on anesthetic level. As a preliminary to its use in SCI, the excitability of the Hoffman reflex (H reflex) has been assessed under several commonly used anesthetics. The H reflex was recorded in the distal foot muscles (dorsal interossei) of adult rats, while the lateral plantar nerve was stimulated. Five different anesthetics were used: ketamine, halothane, Nembutal, Etomidate, and Saffan. Recording and stimulating electrodes were inserted directly through the skin to minimize the surgical procedure for each experiment, allowing repeated recording to be made in the same animal on a weekly basis. Suppression of the H reflex was tested using twin-pulse stimulation. Halothane and ketamine produced suppression of the H response when interpulse intervals were shortened to less than 1 s. The H-reflex suppression profiles recorded under Etomidate, Saffan, and Nembutal anesthesia were less sensitive to the stimulation rate, with little reduction until intervals were 200 ms or less. The suppression profiles of halothane and ketamine resemble that seen in unanesthetized humans, whereas that under the other anesthetics tried here resembles that observed in spinal-cord-injured animals. The results suggest a preferential action of some anesthetics on descending pathways involved in reflex modulation and the importance of assessing reflex excitability under anesthetics such as ketamine or halothane.

Olfactory ensheathing cells promote locomotor recovery after delayed transplantation into transected spinal cord.

We demonstrated recently that transplantation of olfactory ensheathing cells from the nasal olfactory mucosa can promote axonal regeneration after complete transection of the spinal cord in adult rat. Ten weeks after transection and transplantation there was significant recovery of locomotor behaviour and restoration of descending inhibition of spinal cord reflexes, accompanied by growth of axons across the transection site, including serotonergic axons arising from the brainstem raphe nuclei. The present experiment was undertaken to determine whether olfactory ensheathing cells from the olfactory mucosa are capable of promoting regeneration when transplanted into the spinal cord 4 weeks after transection. Under general anaesthesia, thoracic spinal cord at the T10 level was transected completely in adult rats. Four weeks later, the scar tissue and cavities at the transection site were removed to create a 3-4 mm gap. Into this gap, between the cut surfaces of the spinal cord, pieces of olfactory lamina propria were placed. Ten weeks later, the locomotor activity of these animals was significantly improved compared with control animals, which received implants of either pieces of nasal respiratory lamina propria or collagen (Basso, Beattie, Bresnahan Locomotor Rating Scale scores 4.3 + 0.8, n = 6 versus 1.0 + 0.2, n = 10, respectively; P < 0.001). Ten weeks after transplantation the behavioural recovery was still improving. Regrowth of brainstem raphe axons across the transplant site was shown by the presence of serotonergic axons in the spinal cord caudal to the transection site, and by retrograde labelling of cells in the nucleus raphe magnus after injections of fluorogold into the caudal spinal cord. Neither serotonergic axons nor labelled brainstem cells were observed in the control animals. These results indicate that olfactory ensheathing cells from the nasal olfactory lamina propria have the ability to promote spinal cord regeneration when transplanted 4 weeks after complete transection. Olfactory ensheathing cells are accessible and available in the human nose; the present study further supports clinical use of these cells in repairing the human spinal cord via autologous transplantation.