Site Of Nerve Injury Research Articles

The Role of High-Resolution Ultrasound in the Diagnosis of Nerve Trauma New Perspective: A Preliminary Systematic Review and Meta-Analysis of the Recent Evidence.

Precise localization of peripheral nerve injuries and evaluation of their prognosis based on clinical and electrodiagnostic examinations are particularly challenging in the acute phase. High-resolution ultrasound (HRUS) may offer a viable and cost-effective imaging option for assessing the morphology of nerve injuries. Consequently, a systematic review and meta-analysis of studies on the use of ultrasound for diagnosing traumatic nerve injuries were conducted. A total of 15 studies were included, reporting the most recent findings on using HRUS in the diagnosis of traumatic nerve injury. These studies assessed the diagnostic test accuracy of ultrasound for the detection of traumatic nerve injury in 272 participants, with the cross-sectional area at the site of traumatic nerve injury also reported in 1,249 participants. The pooled sensitivity and specificity of the included studies were 92% confidence interval (CI) (0.89-0.95) and 86% CI (0.82-0.89), respectively. The positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 13.76 CI (1.41-134.34), 0.08 CI (0.03-0.18), and 286.23 CI (21.22-3,860.40), respectively. In the summary of the receiver operating characteristic curve, the area under the curve was 0.986, and the Q* index was 0.949. Based on the current literature, HRUS has shown promising results in addition to its availability and feasibility. HRUS can serve as a valuable complement to clinical and electrodiagnostic examinations for diagnosing traumatic peripheral nerve injuries. Further research is recommended to better understand the ultrasound characteristics of these injuries.

Activation of TGR5 in the injured nerve site according to a prevention protocol mitigates partial sciatic nerve ligation-induced neuropathic pain by alleviating neuroinflammation.

Neuropathic pain is a pervasive medical challenge currently lacking effective treatment options. Molecular changes at the site of peripheral nerve injury contribute to both peripheral and central sensitization, critical components of neuropathic pain. This study explores the role of the G-protein-coupled bile acid receptor (GPBAR1 or TGR5) in the peripheral mechanisms underlying neuropathic pain induced by partial sciatic nerve ligation in male mice. TGR5 was upregulated in the injured nerve site and predominantly colocalized with macrophages. Perisciatic nerve administration of the TGR5 agonist, INT-777 according to a prevention protocol (50 μg/μL daily from postoperative day [POD] 0 to POD6) provided sustained relief from mechanical allodynia and spontaneous pain, whereas the TGR5 antagonist, SBI-115 worsened neuropathic pain. Transcriptome sequencing linked the pain relief induced by TGR5 activation to reduced neuroinflammation, which was further evidenced by a decrease in myeloid cells and pro-inflammatory mediators (eg, CCL3, CXCL9, interleukin [IL]-6, and tumor necrosis factor [TNF] α) and an increase in CD86-CD206+ anti-inflammatory macrophages at POD7. Besides, myeloid-cell-specific TGR5 knockdown in the injured nerve site exacerbated both neuropathic pain and neuroinflammation, which was substantiated by bulk RNA-sequencing and upregulated expression levels of inflammatory mediators (including CCL3, CCL2, IL-6, TNF α, and IL-1β) and the increased number of monocytes/macrophages at POD7. Furthermore, the activation of microglia in the spinal cord on POD7 and POD14 was altered when TGR5 in the sciatic nerve was manipulated. Collectively, TGR5 activation in the injured nerve site mitigates neuropathic pain by reducing neuroinflammation, while TGR5 knockdown in myeloid cells worsens pain by enhancing neuroinflammation.

Skeletal muscle reprogramming enhances reinnervation after peripheral nerve injury

Peripheral Nerve Injuries (PNI) affect more than 20 million Americans and severely impact quality of life by causing long-term disability. PNI is characterized by nerve degeneration distal to the site of nerve injury resulting in long periods of skeletal muscle denervation. During this period, muscle fibers atrophy and frequently become incapable of “accepting” innervation because of the slow speed of axon regeneration post injury. We hypothesize that reprogramming the skeletal muscle to an embryonic-like state may preserve its reinnervation capability following PNI. To this end, we generate a mouse model in which NANOG, a pluripotency-associated transcription factor is expressed locally upon delivery of doxycycline (Dox) in a polymeric vehicle. NANOG expression in the muscle upregulates the percentage of Pax7+ nuclei and expression of eMYHC along with other genes that are involved in muscle development. In a sciatic nerve transection model, NANOG expression leads to upregulation of key genes associated with myogenesis, neurogenesis and neuromuscular junction (NMJ) formation. Further, NANOG mice demonstrate extensive overlap between synaptic vesicles and NMJ acetylcholine receptors (AChRs) indicating restored innervation. Indeed, NANOG mice show greater improvement in motor function as compared to wild-type (WT) animals, as evidenced by improved toe-spread reflex, EMG responses and isometric force production. In conclusion, we demonstrate that reprogramming muscle can be an effective strategy to improve reinnervation and functional outcomes after PNI.

The use of electrical stimulation to enhance recovery following peripheral nerve injury.

Peripheral nerve injury is common and can have devastating consequences. In severe cases, functional recovery is often poor despite surgery. This is primarily due to the exceedingly slow rate of nerve regeneration at only 1-3 mm/day. The local environment in the distal nerve stump supportive of nerve regrowth deteriorates over time and the target end organs become atrophic. To overcome these challenges, investigations into treatments capable of accelerating nerve regrowth are of great clinical relevance and are an active area of research. One intervention that has shown great promise is perioperative electrical stimulation. Postoperative stimulation helps to expedite the Wallerian degeneration process and reduces delays caused by staggered regeneration at the site of nerve injury. By contrast, preoperative "conditioning" stimulation increases the rate of nerve regrowth along the nerve trunk. Over the past two decades, a rich body of literature has emerged that provides molecular insights into the mechanism by which electrical stimulation impacts nerve regeneration. The end result is upregulation of regeneration-associated genes in the neuronal body and accelerated transport to the axon front for regrowth. The efficacy of brief electrical stimulation on patients with peripheral nerve injuries was demonstrated in a number of randomized controlled trials on compressive, transection and traction injuries. As approved equipment to deliver this treatment is becoming available, it may be feasible to deploy this novel treatment in a wide range of clinical settings.

Scratch-collapse test in reflex cervical-elbow syndrome

The scratch-collapse test was proposed in 2008 to detect the level of compression of the ulnar and median nerves in tunnel lesions. Further study of this phenomenon has shown that weakness of the shoulder external rotators occurs in nerve lesions at other levels as well. The scratch-collapse test was studied in 155 patients (mean age 45 years) with unilateral reflex cervical-elbow syndrome, with complaints of different localization. The scratch-collapse test was positive in all patients on the affected side. The localization of the trigger zone depended on the patient’s complaints and was established experimentally. Short-term kneading of the trapezius muscle or voluntary contraction of the forearm muscles on the side of the lesion was used to prove the reflex nature of the cervico-elbow syndrome, resulting in complete recovery of triceps or extensor strength of the first and third finger. In the course of the study, suppression of the scratch-collapse test in reflex cervico-elbow syndrome with proprioceptive stimulation was found. In confirmed carpal tunnel and cubital tunnel syndromes, the phenomenon of suppression of the scratch-collapse test was also observed in response to proprioceptive stimulation. The scratch-collapse test and reflex cervical-elbow syndrome have a common mechanism of occurrence, which is based on the protective reaction of the body in the form of a nociceptive shortening reflex. The scratch-collapse test at skin irritation over the site of nerve injury can be considered as a subthreshold physiologic nociceptive reflex. Based on the theory of prognostic action of the nociceptive system, cervicolumbar reflex syndrome is a pathologic nociceptive reflex. Scratchcollapse test suppression phenomenon and recovery of muscle strength in reflexive cervical-elbow syndrome after shortterm kneading of the trapezius muscle are the result of activation of the antinociceptive system in response to proprioceptive stimulation. This suppression phenomenon can be used for the treatment of reflex cervical lockjaw syndrome.

Electromagnetic-responsive targeted delivery scaffold technology has better potential to repair injured peripheral nerves: a narrative review

Peripheral nerve injury with long size defects has been an urgent clinical challenge. With the development of bioengineering, nanotechnology and additive manufacturing technologies, biologic delivery systems have gradually shown great potential for the treatment of peripheral nerve injury. The main problem of general biologic delivery systems is that the loading capacity of biologics is positively correlated with the release rate, and it is more difficult to achieve long-term stable release of high biologics-loaded scaffolds; thus, it is not possible to carry out full-cycle targeted therapy for peripheral nerve injury sites. To solve these problems, the mechanisms of common neurotrophic factors, bioelectrical signals and biomagnetic signals for repairing peripheral nerve injury are discussed in this paper. Moreover, this review summarizes the mechanism of electroactive and magnetoresponsive materials that have significant ability to repair peripheral nerve injury to promote nerve regeneration and provides an overview of the biologic delivery mechanism for repairing peripheral nerve injury in different structural dimensions. It was finally concluded that electromagnetic responsive targeted delivery scaffolds (four-dimensional scaffolds) have good peripheral nerve repair ability, which provides guidance for the clinical application of targeted therapy for peripheral nerve injury.

Localized application of SAG21k-loaded fibrin hydrogels for targeted modulation of the hedgehog pathway in facial nerve injury

Given the broad biological effects of the Hedgehog (Hh) pathway, there is potential clinical value in local application of Hh pathway modulators to restrict pathway activation of target tissues and avoid systemic pathway activation. One option to limit Hh pathway activation is using fibrin hydrogels to deliver pathway modulators directly to tissues of interest, bypassing systemic distribution of the drug. In this study, we loaded the potent Hh pathway agonist, SAG21k, into fibrin hydrogels. We describe the binding between fibrin and SAG21k and achieve sustained release of the drug in vitro. SAG21k-loaded fibrin hydrogels exhibit strong biological activity in vitro, using a pathway-specific reporter cell line. To test in vivo activity, we used a mouse model of facial nerve injury. Application of fibrin hydrogels is a common adjunct to surgical nerve repair, and the Hh pathway is known to play an important role in facial nerve injury and regeneration. Local application of the Hh pathway agonist SAG21k using a fibrin hydrogel applied to the site of facial nerve injury successfully activates the Hh pathway in treated nerve tissue. Importantly, this method appears to avoid systemic pathway activation when Hh-responsive organs are analyzed for transcriptional pathway activation. This method of local tissue Hh pathway agonist administration allows for effective pathway targeting surgically accessible tissues and may have translational value in situations where supranormal pathway activation is therapeutic.

Fabrication of Au-polydopamine blackspheres-loaded PLLA-(silk fibroin) scaffold with photothermal conversion in NIR-II biowindows for deep nerve regeneration

Near infrared second region (NIR II) is applied in deep tissue imaging and tumor therapy. TRPV1 ion channels in cell membrane are widely distributed in nerve tissue, and opened with thermal stimulation, inducing Ca2+ influx. Gold-polydopamine (PDA) blackspheres (AuPBs) with good NIR II absorption and photothermal conversion were prepared by self-oxidation–reduction of dopamine and chlorauric acid, and then loaded on PLLA-SF parallel films (PSPF), which were then curved into nerve scaffolds (PSPF@AuPBs). After this scaffold implantation in sciatic nerve injury site (a depth of more than 1 cm under the skin), PDA in AuPBs relieved inflammatory response in injury site, leading to higher VEGF expression and new-vessels formation; furthermore, TRPV1 ion channels in Schwann cells (SCs) were periodically opened under NIR II irradiation to achieve effect of Ca2+ influx, activating SCs to highly express BDNF and NGF, and then promoting arrangement and myelination of SCs, nerve regeneration and functional recovery. These results suggested that our fabricated PSPF@AuPBs, as an effective NIR II adsorption platform, could provide a good photothermal conversion therapy to improve deep tissue regeneration.

Infraorbital nerve injury triggers sex-specific neuroimmune responses in the peripheral trigeminal pathway and common pain behaviours

Trigeminal neuropathic pain is emotionally distressing and disabling. It presents with allodynia, hyperalgesia and dysaesthesia. In preclinical models it has been assumed that cephalic nerve constriction injury shows identical molecular, cellular, and sex dependent neuroimmune changes as observed in extra-cephalic injury models. This study sought empirical evidence for such assumptions using the infraorbital nerve chronic constriction model (ION-CCI). We compared the behavioural consequences of nerve constriction with: (i) the temporal patterns of recruitment of macrophages and T-lymphocytes at the site of nerve injury and in the trigeminal ganglion; and (ii) the degree of demyelination and axonal reorganisation in the injured nerve. Our data demonstrated that simply testing for allodynia and hyperalgesia as is done in extra-cephalic neuropathic pain models does not provide access to the range of injury-specific nociceptive responses and behaviours reflective of the experience of trigeminal neuropathic pain. Similarly, trigeminal neuroimmune changes evoked by nerve injury are not the same as those identified in models of extra-cephalic neuropathy. Specifically, the timing, magnitude, and pattern of ION-CCI evoked macrophage and T-lymphocyte activity differs between the sexes.

MSR405: Inhibiting Neuroinflammation after Spinal Cord Injury in Rats.

The treatment of spinal cord injury (SCI) is often ineffective. Additionally, SCI-induced inflammation leads to secondary injury. Current anti-inflammatory hydrophilic drugs fail to reach the nerve injury site due to the blood-brain barrier. Here, we synthesized MSR405, a new lipophilic unsaturated fatty acid derivative of Radix Isatidis and investigated its therapeutic effect in SCI model rats. Furthermore, we systematically investigated its structure, toxicity, anti-inflammatory effect, and the underlying mechanism. MSR405 was injected into the abdominal cavity of the Sprague Dawley SCI model rats, and the effect on their behavioral scores and pathology was estimated to assess the status of neurological inflammation. Our data show that MSR405 treatment significantly improved the motor function of SCI rats, and markedly suppressed the associated neuroinflammation. Moreover, MSR405 could attenuate LPS-induced inflammatory response in BV2 cells (Mouse microglia cells) in vitro. Mechanistically, MSR405 inhibits proinflammatory cytokines, supporting the anti-inflammatory response. Additionally, MSR405 can significantly block the TLR4/NF-κB signaling pathway and nitric oxide production. In summary, MSR405 reduces inflammation in SCI rats through the TLR4/NF-κB signal cascade and can inhibit neuroinflammation after spinal cord injury.

Pharmacological blockade of cannabinoid type II receptors and mesenchymal stem cell transplantation in a model of peripheral neuropathic pain

Objective. To evaluate the anti-nociceptive and reparative effects of adipose-derived mesenchymal stem cells (ADMSCs) under the pharmacological blockade of cannabinoid CB2 receptors in a model of peripheral neuropathic pain.Material and methods. In 40 male Wistar rats, modeling of peripheral neuropathy (NP) was performed by excising a sciatic nerve. On day 7 of the study, ADMSCs (1 × 106 cells/kg) were transplanted into the area of sciatic nerve injury without additional influences or after administration of the CB2 receptor antagonist AM630, as well as after incubation with AM630. Within 90 days, nociceptive sensitivity was studied, as well as a detailed analysis of gait using CatWalk XT (Noldus, Netherlands). On day 21 and day 90, histostructure of the distal segment of the sciatic nerve was assessed.Results. Pharmacological blockade of CB2 receptors both on the ADMSCs and in the soft tissues surrounding the site of sciatic nerve injury led to a decrease in withdrawal threshold and withdrawal latency from day 28 of the study compared with the group of rats with NP and transplantation of ADMSCs only. Local injection of AM630 before transplantation of ADMSCs contributed to the development of NP-induced gait disturbances and increase of the number of damaged nerve fibers in the distal segment of sciatic nerve. Transplantation of ADMSCs pretreated with AM630 did not significantly affect the rate of recovery of gait parameters, and decreased the number of damaged nerve fibers by day 90 of study.Conclusion. Blockade of CB2 receptors, both on the membranes of MSCs and in the area of damage to the peripheral nerve, has a negative effect on the development of the anti-nociceptive and reparative effects of MSCs.

Clinical associations of corneal neuromas with ocular surface diseases.

Corneal neuromas, also termed microneuromas, refer to microscopic, irregularly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury. The formation of corneal neuromas results from damage to corneal nerves, such as following corneal pathology or corneal or intraocular surgeries. Initially, denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers, and later injured axons regenerate and new sprouts called neuromas develop. In recent years, analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy, a non-invasive imaging technique with microscopic resolution, has been used to evaluate corneal neuropathy and ocular surface dysfunction. Corneal neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes, and are a promising surrogate biomarker for ocular surface diseases, such as neuropathic corneal pain, dry eye disease, diabetic corneal neuropathy, neurotrophic keratopathy, Sjögren's syndrome, bullous keratopathy, post-refractive surgery, and others. In this review, we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas, as well as elaborated on their pathogenesis, visualization via in vivo confocal microscopy, and utility in monitoring treatment efficacy. As current quantitative analysis on neuromas mainly relies on manual annotation and quantification, which is user-dependent and labor-intensive, future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner, allowing it to be applied in clinical settings more efficiently. Combining imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.

Chapter 3 - The role of electrodiagnosis in focal neuropathies

Electrodiagnostic (EDX) testing plays an important role in confirming a mononeuropathy, localizing the site of nerve injury, defining the pathophysiology, and assessing the severity and prognosis. The combination of nerve conduction studies (NCS) and needle electromyography findings provides the necessary information to fully assess a nerve. The pattern of NCS abnormalities reflects the underlying pathophysiology, with focal slowing or conduction block in neuropraxic injuries and reduced amplitudes in axonotmetic injuries. Needle electromyography findings, including spontaneous activity and voluntary motor unit potential changes, complement the NCS findings and further characterize chronicity and degree of axon loss and reinnervation. EDX is used as an objective marker to follow the progression of a mononeuropathy over time.

Chapter 6 - Ulnar neuropathy

Ulnar neuropathy at the elbow is the second most common compressive neuropathy. Less common, although similarly disabling, are ulnar neuropathies above the elbow, at the forearm, and the wrist, which can present with different combinations of intrinsic hand muscle weakness and sensory loss. Electrodiagnostic studies are moderately sensitive in diagnosing ulnar neuropathy, although their ability to localize the site of nerve injury is often limited. Nerve imaging with ultrasound can provide greater localization of ulnar injury and identification of specific anatomical pathology causing nerve entrapment. Specifically, imaging can now reliably distinguish ulnar nerve entrapment under the humero-ulnar arcade (cubital tunnel) from nerve injury at the retro-epicondylar groove. Both these pathologies have historically been diagnosed as either "ulnar neuropathy at the elbow," which is non-specific, or "cubital tunnel syndrome," which is often erroneous. Natural history studies are few and limited, although many cases of mild-moderate ulnar neuropathy at the elbow appear to remit spontaneously. Conservative management, perineural steroid injections, and surgical release have all been studied in treating ulnar neuropathy at the elbow. Despite this, questions remain about the most appropriate management for many patients, which is reflected in the absence of management guidelines.

Incidence of nerve injury following acupuncture treatments in Taiwan

ObjectiveAcupuncture, a widely employed traditional therapeutic modality known for its efficacy in pain alleviation and diverse condition management, may inadvertently result in mechanical nerve injury due to its invasive nature. This research aimed to ascertain the incidence of nerve injuries post-acupuncture, identify associated risk factors, and map the distribution of nerve injury sites. MethodsA case-control study nested in the National Health Insurance Research Database (NHIRD) 2000–2018 two million cohort was conducted. Patients previously diagnosed with nerve injury, surgery, or degeneration before acupuncture were excluded. Cases were defined as patients receiving acupuncture and seeking medical attention for nerve injury (ICD9-CM code 950–957) within 14 days post-procedure, while control groups comprised patients undergoing acupuncture without subsequent adverse events. Invasive treatments prior to adverse events and adverse events occurring more than 14 days post-acupuncture were excluded. To ensure case-control comparability, factors such as age, gender, socioeconomic status, and medical facility environment were controlled using propensity score matching. ResultsThe study encompassed 14,507,847 acupuncture treatments administered to 886,753 patients, with 8361 instances of post-acupuncture nerve injury identified, representing an incidence rate of approximately 5.76 per 10,000 procedures. Age emerged as a significant risk factor, with the adjusted odds ratios escalating with age. Several comorbidities including diabetes, hypothyroidism, liver cirrhosis, chronic kidney disease, herpes zoster, hepatitis virus, rheumatoid arthritis, systemic lupus erythematosus, dementia, and cerebrovascular accidents were associated with an elevated risk of nerve injury post-acupuncture. ConclusionThis study underscores the importance of meticulous patient profiling and cautious therapeutic approach in acupuncture, considering the evident influence of various demographic, systemic, and treatment-related factors on the incidence of nerve injuries.

Voluntary wheel running prevents formation of membrane attack complexes and myelin degradation after peripheral nerve injury

Regular aerobic activity is associated with a reduced risk of chronic pain in humans and rodents. Our previous studies in rodents have shown that prior voluntary wheel running can normalize redox signaling at the site of peripheral nerve injury, attenuating subsequent neuropathic pain. However, the full extent of neuroprotection offered by voluntary wheel running after peripheral nerve injury is unknown. Here, we show that six weeks of voluntary wheel running prior to chronic constriction injury (CCI) reduced the terminal complement membrane attack complex (MAC) at the sciatic nerve injury site. This was associated with increased expression of the MAC inhibitor CD59. The levels of upstream complement components (C3) and their inhibitors (CD55, CR1 and CFH) were altered by CCI, but not increased by voluntary wheel running. Since MAC can degrade myelin, which in turn contributes to neuropathic pain, we evaluated myelin integrity at the sciatic nerve injury site. We found that the loss of myelinated fibers and decreased myelin protein which occurs in sedentary rats following CCI was not observed in rats with prior running. Substitution of prior voluntary wheel running with exogenous CD59 also attenuated mechanical allodynia and reduced MAC deposition at the nerve injury site, pointing to CD59 as a critical effector of the neuroprotective and antinociceptive actions of prior voluntary wheel running. This study links attenuation of neuropathic pain by prior voluntary wheel running with inhibition of MAC and preservation of myelin integrity at the sciatic nerve injury site.

A feasibility study transplanting macrophages to a segmental nerve injury.

Promoting regeneration after segmental nerve injury repair is a challenge, but improving angiogenesis could be beneficial. Macrophages facilitate regeneration after injury by promoting angiogenesis. Our aim in this study was to evaluate the feasibility and effects of transplanting exogenous macrophages to a segmental nerve injury. Bone marrow-derived cells were harvested from donor mice and differentiated to macrophages (BMDM), then suspended within fibrin hydrogels to facilitate BMDM transplantation. BMDM survival was characterized in vitro. The effect of this BMDM fibrin hydrogel construct at a nerve injury site was assessed using a mouse sciatic nerve gap injury. Mice were equally distributed to "fibrin+Mφ" (fibrin hydrogels containing culture medium and BMDM) or "fibrin" hydrogel control (fibrin hydrogels containing culture medium alone) groups. Flow cytometry (n = 3/group/endpoint) and immunohistochemical analysis (n = 5/group/endpoint) of the nerve gap region were performed at days 3, 5, and 7 after repair. Incorporating macrophage colony-stimulating factor (M-CSF) improved BMDM survival and expansion. Transplanted BMDM survived for at least 7 days in a nerve gap (~40% retained at day 3 and ~15% retained at day 7). From transplantation, macrophage quantities within the nerve gap were elevated when comparing fibrin+Mφ with fibrin control (~25% vs. 3% at day 3 and ~14% vs. 6% at day 7). Endothelial cells increased by about fivefold within the nerve gap, and axonal extension into the nerve gap increased almost twofold for fibrin+Mφ compared with fibrin control. BMDM suspended within fibrin hydrogels at a nerve gap do not impair regeneration.

A spatially specified systems pharmacology therapy for axonal recovery after injury.

There are no known drugs or drug combinations that promote substantial central nervous system axonal regeneration after injury. We used systems pharmacology approaches to model pathways underlying axonal growth and identify a four-drug combination that regulates multiple subcellular processes in the cell body and axons using the optic nerve crush model in rats. We intravitreally injected agonists HU-210 (cannabinoid receptor-1) and IL-6 (interleukin 6 receptor) to stimulate retinal ganglion cells for axonal growth. We applied, in gel foam at the site of nerve injury, Taxol to stabilize growing microtubules, and activated protein C to clear the debris field since computational models predicted that this drug combination regulating two subcellular processes at the growth cone produces synergistic growth. Physiologically, drug treatment restored or preserved pattern electroretinograms and some of the animals had detectable visual evoked potentials in the brain and behavioral optokinetic responses. Morphology experiments show that the four-drug combination protects axons or promotes axonal regrowth to the optic chiasm and beyond. We conclude that spatially targeted drug treatment is therapeutically relevant and can restore limited functional recovery.

Imaging traumatic facial nerve injuries: a narrative review of current strategies and future directions for cranial nerve imaging

Traumatic facial nerve injuries can result in temporary or permanent loss of function. Restoration of facial expression may occur spontaneously or require surgical intervention. Although thorough examination and history can localize the site of facial nerve damage, it can be difficult to predict if and when recovery will occur. This is salient because the window for optimal outcomes from surgical re-neurotization can be as short as 1 to 2 years, after which functional loss may be irreversible. It is essential to offer patients the most appropriate treatment plan based on prognosis, and imaging plays an essential role in localizing the site and morphology of nerve injury. Multiple imaging modalities have been used to evaluate the facial nerve, including Computed Tomography (CT) and, more recently, advanced Magnetic Resonance Imaging (MRI) and Ultrasound (US). CT and MRI are more commonly implemented; however, Diffusion Tensor Tractography, high-resolution US, and functional US are gaining traction for studying cranial nerve pathology. Until recently, the morphology of facial nerve and other cranial nerve injuries could only be inferred using non-invasive diagnostic techniques. With the advent of newer imaging technologies and techniques to examine nerves, more refined assessment and prognostic information is now possible. This article reviews up-to-date cranial nerve imaging techniques from the last ten years and explores future avenues for facial nerve imaging.

Sigma-1 receptor expression in a subpopulation of lumbar spinal cord microglia in response to peripheral nerve injury

Sigma-1 Receptor has been shown to localize to sites of peripheral nerve injury and back pain. Radioligand probes have been developed to localize Sigma-1 Receptor and thus image pain source. However, in non-pain conditions, Sigma-1 Receptor expression has also been demonstrated in the central nervous system and dorsal root ganglion. This work aimed to study Sigma-1 Receptor expression in a microglial cell population in the lumbar spine following peripheral nerve injury. A publicly available transcriptomic dataset of 102,691 L4/5 mouse microglial cells from a sciatic-sural nerve spared nerve injury model and 93,027 age and sex matched cells from a sham model was used. At each of three time points—postoperative day 3, postoperative day 14, and postoperative month 5—gene expression data was recorded for both spared nerve injury and Sham cell groups. For all cells, 27,998 genes were sequenced. All cells were clustered into 12 distinct subclusters and gene set enrichment pathway analysis was performed. For both the spared nerve injury and Sham groups, Sigma-1 Receptor expression significantly decreased at each time point following surgery. At the 5-month postoperative time point, only one of twelve subclusters showed significantly increased Sigma-1 Receptor expression in spared nerve injury cells as compared to Sham cells (p = 0.0064). Pathway analysis of this cluster showed a significantly increased expression of the inflammatory response pathway in the spared nerve injury cells relative to Sham cells at the 5-month time point (p = 6.74e−05). A distinct subcluster of L4/5 microglia was identified which overexpress Sigma-1 Receptor following peripheral nerve injury consistent with neuropathic pain inflammatory response functioning. This indicates that upregulated Sigma-1 Receptor in the central nervous system characterizes post-acute peripheral nerve injury and may be further developed for clinical use in the differentiation between low back pain secondary to peripheral nerve injury and low back pain not associated with peripheral nerve injury in cases where the pain cannot be localized.