Effects of bottom trawling and environmental factors on benthic bacteria, meiofauna and macrofauna communities and benthic ecosystem processes.

Soft sediment marine benthic ecosystems comprise a diverse community of bacteria, meiofauna and macrofauna, which together support a range of ecosystem processes such as biogeochemical cycling. These ecosystems are also fishing grounds for demersal species that are often caught using bottom trawling. This fishing method can have deleterious effects on benthic communities by causing injury or mortality, and through alteration of sediment properties that in turn influence community structure. Although the impacts of bottom trawling on macrofauna are relatively well studied, less is known about the responses of meiofauna and bacteria to such disturbances, or how bottom trawling impacts benthic ecosystem processes. Quantifying trawling impacts against a background of natural environmental variability is also a challenge. To address these questions, we examined effects of bottom trawling and a range of environmental variables (e.g. water chemistry and physical and biochemical surface sediment properties) on a) bacterial, meiofaunal and macrofaunal community structure and b) benthic ecosystem processes (nutrient fluxes, extracellular enzyme activities and carbon turnover and degradation rates). We also investigated the link between the benthic macrofauna community and the same ecosystem processes. While there was a significant effect of bottom trawling intensity on macrofaunal community structure, the same was not seen for bacterial or meiofaunal community composition, which were more affected by environmental factors, such as surface sediment properties. The labile component of the surface sediment carbon pool was higher at highly trawled sites. Carbon degradation rates, extracellular enzyme activities, oxygen fluxes and some nutrient fluxes were significantly affected by trawling, but ecosystem processes were also strongly linked to the abundance of key bioturbators (Macoma balthica, Halicryptus spinulosus, Scoloplos armiger and Pontoporeia femorata). Although benthic ecosystems were affected by a combination of trawling and natural variability, disentangling these showed that the anthropogenic effects were clearest on the larger component of the community, i.e. macrofauna composition, and on ecosystem processes related to sedimentary carbon.

Nerve Tracing in Juvenile Rats: A Feasible Model for the Study of Brachial Plexus Birth Palsy and Cocontractions?

Brachial plexus birth injuries cause diminished motor function in the upper extremity. The most common sequel is internal rotation contracture. A number of these patients also suffer from cocontractions, preventing the use of an otherwise good passive range of motion in the shoulder. One theory behind the co-contracture problem is that injured nerve fibers grow into distal support tissue not corresponding to the proximal support tissue, resulting in reinnervation of the wrong muscle groups. To further elucidate this hypothesis, we used rat neonates to investigate a possible model for the study of cocontractions in brachial plexus birth injuries. Five-day-old rats were subjected to a crush injury to the C5-C6 roots. After a healing period of 4 weeks, the infraspinatus muscle was injected with Fluoro-Gold. A week later, the animals were perfused and spinal cords harvested and sectioned. Differences in the uptake of Fluoro-Gold and NeuN positive cells of between sides of the spinal cord were recorded. We found a larger amount of Fluoro-Gold positive cells on the uninjured side, while the injured side had positive cells dispersed over a longer area in the craniocaudal direction. Our findings indicate that the method can be used to trace Fluoro-Gold from muscle through a neuroma. Our results also indicate that a neuroma in continuity somewhat prevents the correct connection from being established between the motor neuron pool in the spinal cord and target muscle and that some neurons succumb to a crushing injury. We also present future research ideas.

[Spinal neurosurgery: radiculopathy and myelopathy]. / Spinal neurokirurgi på grund av radikulopati och myelopati.

The field of spinal neurosurgery covers degenerative conditions and trauma as well as tumors, malformations and vascular disorders of spine and spinal cord. This article focuses on the Swedish spinal neurosurgical care regarding radiculopathy and myelopathy. Disc herniation, foraminal stenosis, spinal stenosis and spinal cord compression due to degenerative disorders or tumors are discussed. Treatment options such as anterior cervical decompression and fusion, posterior forami-notomy, laminectomy and approaches to spinal intradural tumors are briefly presented. The aim is to present symptoms, diagnostics and treatment options of common conditions to facilitate early detection and referral to neurosurgical centers to avoid delayed dia-gnosis and neurological impairment.

Dura Management Strategies in the Surgical Treatment of Adult Chiari Type I Malformation: A Retrospective, Multicenter, Population-Based Parallel Cohort Case Series.

BACKGROUND: Symptomatic Chiari I malformation is treated with suboccipital decompression and C1 laminectomy. However, whether the dura should be opened (durotomy) or enlarged with a graft (duraplasty) remains unclear. OBJECTIVE: To compare outcomes in adult Chiari I malformation patients treated with duraplasty, durotomy, or without dural opening ("mini-decompression"). METHODS: A retrospective, multicenter, population-based cohort study was performed of all adult patients surgically treated for a Chiari I malformation at 3 regional neurosurgical centers between 2005 and 2017. Three different dura management strategies were favored by the participating hospitals, with data stratified accordingly. The primary outcome was measured using the Chicago Chiari Outcome Scale (CCOS), dichotomized into favorable (CCOS ≥13) or unfavorable (CCOS ≤12). Propensity score matching was used to adjust for potential confounders in outcome comparisons. RESULTS: In total, 318 patients were included, of whom 52% were treated with duraplasty, 37% with durotomy, and 11% with mini-decompression. In total, 285 (90%) showed a favorable surgical outcome (CCOS ≥13). Duraplasty was associated with more favorable CCOS and shorter hospital stay compared with durotomy, both in unadjusted (93% vs 84%. P = .018 and 6.0 vs 8.0 days, P < .001) and adjusted analyses (92% vs 84%, P = .044 and 6.0 vs 8.0 days, P < .001). Mini-decompression was excluded from the adjusted analyses because of its small sample size. CONCLUSION: In this study of adult Chiari I malformation, posterior fossa decompression with duraplasty was associated with more favorable postoperative outcome, as determined by the CCOS, compared with posterior fossa decompression with durotomy alone.

Sonification of Complex Spectral Structures.

In this article, we present our work on the sonification of notated complex spectral structures. It is part of a larger research project about the design of a new notation system for representing sound-based musical structures. Complex spectral structures are notated with special symbols in the scores, which can be digitally rendered so that the user can hear key aspects of what has been notated. This hearing of the notated data is significantly different from reading the same data, and reveals the complexity hidden in its simplified notation. The digitally played score is not the music itself but can provide essential information about the music in ways that can only be obtained in sounding form. The playback needs to be designed so that the user can make relevant sonic readings of the sonified data. The sound notation system used here is an adaptation of Thoresen and Hedman's spectromorphological analysis notation. Symbols originally developed by Lasse Thoresen from Pierre Schaeffer's typo-morphology have in this system been adapted to display measurable spectral features of timbrel structure for the composition and transcription of sound-based musical structures. Spectrum category symbols are placed over a spectral grand-staff that combines indications of pitch and frequency values for the combined display of music related to pitch-based and spectral values. Spectral features of a musical structure such as spectral width and density are represented as graphical symbols and sonically rendered. In perceptual experiments we have verified that users can identify spectral notation parameters based on their sonification. This confirms the main principle of sonification that is that the data/dimensions relations in one domain, in our case notated representation of spectral features, are transformed in perceived relations in the audio domain, and back.

Hippocampal Expression of Cytochrome P450 1B1 in Penetrating Traumatic Brain Injury.

Hippocampal dysfunction contributes to multiple traumatic brain injury sequala. Female rodents' outcome is superior to male which has been ascribed the neuroprotective sex hormones 17ß-estradiol and progesterone. Cytochrome P450 1B1 (CYP1B1) is an oxidative enzyme influencing the neuroinflammatory response by creating inflammatory mediators and metabolizing neuroprotective 17ß-estradiol and progesterone. In this study, we aimed to describe hippocampal CYP1B1 mRNA expression, protein presence of CYP1B1 and its key redox partner Cytochrome P450 reductase (CPR) in both sexes, as well as the effect of penetrating traumatic brain injury (pTBI). A total 64 adult Sprague Dawley rats divided by sex received pTBI or sham-surgery and were assigned survival times of 1-, 3-, 5- or 7 days. CYP1B1 mRNA was quantified using in-situ hybridization and immunohistochemistry performed to verify protein colocalization. CYP1B1 mRNA expression was present in all subregions but greatest in CA2 irrespective of sex, survival time or intervention. At 3-, 5- and 7 days post-injury, expression in CA2 was reduced in male rats subjected to pTBI compared to sham-surgery. Females subjected to pTBI instead exhibited increased expression in all CA subregions 3 days post-injury, the only time point expression in CA2 was greater in females than in males. Immunohistochemical analysis confirmed neuronal CYP1B1 protein in all hippocampal subregions, while CPR was limited to CA1 and CA2. CYP1B1 mRNA is constitutively expressed in both sexes. In response to pTBI, females displayed a more urgent but brief regulatory response than males. This indicates there may be sex-dependent differences in CYP1B1 activity, possibly influencing inflammation and neuroprotection in pTBI.

Artificial spider silk supports and guides neurite extension in vitro.

Surgical intervention with the use of autografts is considered the gold standard to treat peripheral nerve injuries. However, a biomaterial that supports and guides nerve growth would be an attractive alternative to overcome problems with limited availability, morbidity at the site of harvest, and nerve mismatches related to autografts. Native spider silk is a promising material for construction of nerve guidance conduit (NGC), as it enables regeneration of cm-long nerve injuries in sheep, but regulatory requirements for medical devices demand synthetic materials. Here, we use a recombinant spider silk protein (NT2RepCT) and a functionalized variant carrying a peptide derived from vitronectin (VN-NT2RepCT) as substrates for nerve growth support and neurite extension, using a dorsal root ganglion cell line, ND7/23. Two-dimensional coatings were benchmarked against poly-d-lysine and recombinant laminins. Both spider silk coatings performed as the control substrates with regards to proliferation, survival, and neurite growth. Furthermore, NT2RepCT and VN-NT2RepCT spun into continuous fibers in a biomimetic spinning set-up support cell survival, neurite growth, and guidance to an even larger extent than native spider silk. Thus, artificial spider silk is a promising biomaterial for development of NGCs.

Acute necrotizing encephalopathy with SARS-CoV-2 RNA confirmed in cerebrospinal fluid.

Here, we report a case of COVID-19-related acute necrotizing encephalopathy where SARS-CoV-2 RNA was found in CSF 19 days after symptom onset after testing negative twice. Although monocytes and protein levels in CSF were only marginally increased, and our patient never experienced a hyperinflammatory state, her neurologic function deteriorated into coma. MRI of the brain showed pathologic signal symmetrically in central thalami, subinsular regions, medial temporal lobes, and brain stem. Extremely high concentrations of the neuronal injury markers neurofilament light and tau, as well as an astrocytic activation marker, glial fibrillary acidic protein, were measured in CSF. Neuronal rescue proteins and other pathways were elevated in the in-depth proteomics analysis. The patient received IV immunoglobulins and plasma exchange. Her neurologic status improved, and she was extubated 4 weeks after symptom onset. This case report highlights the neurotropism of SARS-CoV-2 in selected patients and emphasizes the importance of repeated lumbar punctures and CSF analyses in patients with suspected COVID-19 and neurologic symptoms.

Diffuse Axonal Injury in the Rat Brain: Axonal Injury and Oligodendrocyte Activity Following Rotational Injury.

Traumatic brain injury (TBI) commonly results in primary diffuse axonal injury (DAI) and associated secondary injuries that evolve through a cascade of pathological mechanisms. We aim at assessing how myelin and oligodendrocytes react to head angular-acceleration-induced TBI in a previously described model. This model induces axonal injuries visible by amyloid precursor protein (APP) expression, predominantly in the corpus callosum and its borders. Brain tissue from a total of 27 adult rats was collected at 24 h, 72 h and 7 d post-injury. Coronal sections were prepared for immunohistochemistry and RNAscope® to investigate DAI and myelin changes (APP, MBP, Rip), oligodendrocyte lineage cell loss (Olig2), oligodendrocyte progenitor cells (OPCs) (NG2, PDGFRa) and neuronal stress (HSP70, ATF3). Oligodendrocytes and OPCs numbers (expressed as percentage of positive cells out of total number of cells) were measured in areas with high APP expression. Results showed non-statistically significant trends with a decrease in oligodendrocyte lineage cells and an increase in OPCs. Levels of myelination were mostly unaltered, although Rip expression differed significantly between sham and injured animals in the frontal brain. Neuronal stress markers were induced at the dorsal cortex and habenular nuclei. We conclude that rotational injury induces DAI and neuronal stress in specific areas. We noticed indications of oligodendrocyte death and regeneration without statistically significant changes at the timepoints measured, despite indications of axonal injuries and neuronal stress. This might suggest that oligodendrocytes are robust enough to withstand this kind of trauma, knowledge important for the understanding of thresholds for cell injury and post-traumatic recovery potential.

Temporal gene expression changes after acute and delayed ventral root avulsion-reimplantation.

BACKGROUND: In a model of injured spinal motor neurons where the avulsed spinal nerve is surgically reimplanted, useful regrowth of the injured nerve follows, both in animal experiments and clinical cases. This has led to surgical reimplantation strategies with subsequent partial functional motoric recovery. Still, the ideal time point for successful regeneration after reimplantation and the specific genetic profile of this time point is not known. OBJECTIVE: To explore the temporal gene expression of the whole genome in the ventral spinal cord after reimplantation at different time points after avulsion. METHODS: Totally 18 adult rats were subjected to avulsion of the left L5 root only (N = 3), avulsion followed by acute spinal reimplantation (N = 3), avulsion followed by 24 h (N = 3) or 48 h (N = 3) delayed reimplantation. Animals were allowed to survive 24 h after their respective surgery whereafter the ventral quadrant of the spinal cord at the operated side was harvested, processed for and analysed with Affymetrix Rat Gene ST 1.0 array followed by statistical analysis of gene expression patternsResults:Specific gene expression patterns were found at different time points after avulsion and reimplantation. Over all, early reimplantation seemed to diminish inflammatory response and support gene regulation related to neuronal activity compared to avulsion only or delayed reimplantation. In addition did gene activity after avulsion-reimplantation correspond to regeneration-associated genes typical for regeneration in the peripheral nervous system. CONCLUSIONS: Our study reveal that genetic profiling after this kind of injury is possible, that specific and distinct expression patterns can be found with early reimplantation being favourable over late and that regenerative activity in this kind of injury bears hallmark typical for peripheral nerve regeneration. These findings can be useful in elucidating specific genetic expression typical for successful nerve regeneration, hopefully not only in this specific model but in the nervous system in general.

Stable isotopes reveal the effect of trawl fisheries on the diet of commercially exploited species.

Bottom trawling can change food availability for benthivorous demersal species by (i) changing benthic prey composition through physical seabed impacts and (ii) by removing overall benthic consumer biomass increasing the net availability of benthic prey for remaining individuals. Thus trawling may both negatively and positively influence the quantity and quality of food available. Using δ 13C and δ 15N we investigated potential diet changes of three commercially exploited species across trawling gradients in the Kattegat (plaice, dab and Norway lobster (Nephrops)) and the Irish Sea (Nephrops). In the Kattegat, trawling affected primarily the biomass of benthic consumers, lowering competition. Nephrops showed significant positive relationships for δ 13C and a domed relationship for δ 15N with trawling. In the Irish Sea, intense trawling had a negative effect on benthic prey. δ 13C and δ 15N thus showed the inverse relationships to those observed in the Kattegat. Plaice from the Kattegat, showed a significant relationship with trawling intensity for δ 13C, but not for δ 15N. No relationship was found for dab. Changes of δ 13C and δ 15N correlated with changes in condition of species. The results show that the removal of demersal competitors and benthos by trawling can change the diets of commercial species, ultimately affecting their body condition.

Expression of Semaphorins, Neuropilins, VEGF, and Tenascins in Rat and Human Primary Sensory Neurons after a Dorsal Root Injury.

Dorsal root injury is a situation not expected to be followed by a strong regenerative growth, or growth of the injured axon into the central nervous system of the spinal cord, if the central axon of the dorsal root is injured but of strong regeneration if subjected to injury to the peripherally projecting axons. The clinical consequence of axonal injury is loss of sensation and may also lead to neuropathic pain. In this study, we have used in situ hybridization to examine the distribution of mRNAs for the neural guidance molecules semaphorin 3A (SEMA3A), semaphorin 3F (SEMA3F), and semaphorin 4F (SEMA4F), their receptors neuropilin 1 (NP1) and neuropilin 2 (NP2) but also for the neuropilin ligand vascular endothelial growth factor (VEGF) and Tenascin J1, an extracellular matrix molecule involved in axonal guidance, in rat dorsal root ganglia (DRG) after a unilateral dorsal rhizotomy (DRT) or sciatic nerve transcetion (SNT). The studied survival times were 1-365 days. The different forms of mRNAs were unevenly distributed between the different size classes of sensory nerve cells. The results show that mRNA for SEMA3A was diminished after trauma to the sensory nerve roots in rats. The SEMA3A receptor NP1, and SEMA3F receptor NP2, was significantly upregulated in the DRG neurons after DRT and SNT. SEMA4F was upregulated after a SNT. The expression of mRNA for VEGF in DRG neurons after DRT showed a significant upregulation that was high even a year after the injuries. These data suggest a role for the semaphorins, neuropilins, VEGF, and J1 in the reactions after dorsal root lesions.

Cellular High-Energy Cavitation Trauma - Description of a Novel In Vitro Trauma Model in Three Different Cell Types.

The mechanisms involved in traumatic brain injury have yet to be fully characterized. One mechanism that, especially in high-energy trauma, could be of importance is cavitation. Cavitation can be described as a process of vaporization, bubble generation, and bubble implosion as a result of a decrease and subsequent increase in pressure. Cavitation as an injury mechanism is difficult to visualize and model due to its short duration and limited spatial distribution. One strategy to analyze the cellular response of cavitation is to employ suitable in vitro models. The flyer-plate model is an in vitro high-energy trauma model that includes cavitation as a trauma mechanism. A copper fragment is accelerated by means of a laser, hits the bottom of a cell culture well causing cavitation, and shock waves inside the well and cell medium. We have found the flyer-plate model to be efficient, reproducible, and easy to control. In this study, we have used the model to analyze the cellular response to microcavitation in SH-SY5Y neuroblastoma, Caco-2, and C6 glioma cell lines. Mitotic activity in neuroblastoma and glioma was investigated with BrdU staining, and cell numbers were calculated using automated time-lapse imaging. We found variations between cell types and between different zones surrounding the lesion with these methods. It was also shown that the injured cell cultures released S-100B in a dose-dependent manner. Using gene expression microarray, a number of gene families of potential interest were found to be strongly, but differently regulated in neuroblastoma and glioma at 24 h post trauma. The data from the gene expression arrays may be used to identify new candidates for biomarkers in cavitation trauma. We conclude that our model is useful for studies of trauma in vitro and that it could be applied in future treatment studies.

Population structure in Atlantic cod in the eastern North Sea-Skagerrak-Kattegat: early life stage dispersal and adult migration.

BACKGROUND: In marine fish species, where pelagic egg and larvae drift with ocean currents, population structure has been suggested to be maintained by larval retention due to hydrographic structuring and by homing of adult fish to natal areas. Whilst natal homing of adults has been demonstrated for anadromous and coral reef fishes, there are few documented examples of philopatric migration in temperate marine fish species. RESULTS: Here, we demonstrate temporally stable genetic differentiation among spawning populations of Atlantic cod (Gadus morhua L.), and present genetic and behavioural evidence for larval drift and philopatric migration in the eastern North Sea-Skagerrak-Kattegat area. We show that juvenile cod collected in the eastern Skagerrak and central Kattegat are genetically similar to cod from offshore spawning areas in the eastern North Sea. Genetic assignment of individual 2-5 year old fish indicates that cod residing at, or migrating towards, spawning areas in Kattegat and the North Sea display philopatric behaviours. CONCLUSIONS: Together these findings suggest a loop between spawning, larval drift and adult return-migrations to spawning areas and underlines that both oceanographic processes and migratory behaviour in the adult phase may be important for stock separation and integrity in marine temperate fishes such as Atlantic cod.

Using vessel monitoring system data to improve systematic conservation planning of a multiple-use marine protected area, the Kosterhavet National Park (Sweden).

When spatial fishing data is fed into systematic conservation planning processes the cost to a fishery could be ensured to be minimal in the zoning of marine protected areas. We used vessel monitoring system (VMS) data to map the distribution of prawn trawling and calculate fishing intensity for 1-ha grid cells, in the Kosterhavet National Park (Sweden). We then used the software Marxan to generate cost-efficient reserve networks that represented every biotope in the Park. We asked what were the potential gains and losses in terms of fishing effort and species conservation of different planning scenarios. Given a conservation target of 10 % representation of each biotope, the fishery need not lose more than 20 % of its fishing grounds to give way to cost-efficient conservation of benthic diversity. No additional reserved area was needed to achieve conservation targets while minimizing fishing costs. We discuss the benefits of using VMS data for conservation planning.

Gender differences in health and aging of Atlantic cod subject to size selective fishery.

We have analyzed health and physiological aging parameters in male and female Atlantic cod, Gadus morhua, captured in Kattegat, Skagerrak and in Öresund. Gender differences were clearly evident in a number of variables. Males had longer liver telomeres and higher catalase activities than females, while females had higher superoxide dismutase activity, liver somatic index and condition factor. Effects of age were found for males where levels of the antioxidant glutathione and telomere length declined with age, indicating physiological aging. Liver somatic index increased and percentage oxidized glutathione decreased with age. Between-site comparisons of males show that percentage oxidized glutathione and catalase were lowest in Kattegat, whereas protein carbonyls and condition factor were higher in Skagerrak. Females, on the other hand, showed no differences between sites or indications of somatic aging or age-related effects in egg quality, indicating that older and larger female cod are healthy and show no changes in eggs with age. In contrast, males showed indications of physiological aging and lower condition than females. The results emphasize the importance of conserving old mature fish, in particular high egg-productive females, when managing fisheries.

An evaluation of three measures of intracranial compliance in traumatic brain injury patients.

PURPOSE: To compare intracranial pressure (ICP) amplitude, ICP slope, and the correlation of ICP amplitude and ICP mean (RAP index) as measures of compliance in a cohort of traumatic brain injury (TBI) patients. METHODS: Mean values of the three measures were calculated in the 2-h periods before and after surgery (craniectomies and evacuations), and in the 12-h periods preceding and following thiopental treatment, and during periods of thiopental coma. The changes in the metrics were evaluated using the Wilcoxon test. The correlations of 10-day mean values for the three metrics with age, admission Glasgow Motor Score (GMS), and Extended Glasgow Outcome Score (GOSe) were evaluated. Patients under and over 60 years old were also compared using the Student t test. The correlation of ICP amplitude with systemic pulse amplitude was analyzed. RESULTS: ICP amplitude was significantly correlated with GMS, and also with age for patients 35 years old and older. The correlations of ICP slope and the RAP index with GMS and with age were not significant. All three metrics indicated significant improvements in compliance following surgery and during thiopental coma. None of the metrics were significantly correlated with outcome, possibly due to confounding effects of treatment factors. The correlation of systemic pulse amplitude with ICP amplitude was low (R = 0.18), only explaining 3 % of the variance. CONCLUSIONS: This study provides further validation for all three of these features of the ICP waveform as measures of compliance. ICP amplitude had the best performance in these tests.

Activating transcription factor 3, a useful marker for regenerative response after nerve root injury.

Activating transcription factor 3 (ATF3) is induced in various tissues in response to stress. In this experiment, ATF3 expression was studied in adult rats subjected either to a dorsal or ventral root avulsion (VRA; L4-6), or sciatic nerve transection (SNT). Post-operative survival times varied between 1.5 h and 3 weeks. In additional experiments an avulsed ventral root was directly replanted to the spinal cord. Dorsal root ganglias (DRGs) from humans exposed to traumatic dorsal root avulsions were also examined. After SNT ATF3 immunoreactivity (ATF3 IR) was detected in a few DRG neurons already 6 h after the lesion. After 24 h the number had clearly increased and still at 3 weeks DRG neurons remained labeled. In the ventral horn, ATF3 IR in motoneurons (MN) was first detected 24 h after the SNT, and still 3 weeks post-operatively lesioned MN showed ATF3 labeling. After a VRA many spinal MN showed ATF3 IR already after 3 h, and after 6 h all MN were labeled. At 3 weeks a majority of the lesioned MN had died, but all the remaining ones were labeled. When an avulsed ventral root was directly replanted, MN survived and were still labeled at 5 weeks. In DRG, a few neurons were labeled already at 1.5 h after a dorsal root avulsion. At 24 h the number had increased but still only a minority of the neurons were labeled. At 3 days the number of labeled neurons was reduced, and a further reduction was at hand at 7 days and 3 weeks. In parallel, in humans, 3 days after a traumatic dorsal root avulsion, only a few DRG neurons showed ATF3 IR. At 6 weeks no labeled neurons could be detected. These facts imply that ATF3 response to axotomy involves a distance-dependent mechanism. ATF3 also appears to be a useful and reliable neuronal marker of nerve lesions even in humans. In addition, ATF3 up-regulation in both motor and sensory neurons seems to be linked to regenerative competence.