Peripheral Nerve Trunks Research Articles

Chronic neuropathic pain in spinal cord injured patients: What is the effectiveness of surgical treatments excluding central neurostimulations?

Objectives Analyzing the literature and elaborating recommendations on the following topics: relevance of dorsal root entry zone (DREZ) lesions, surgical treatment for posttraumatic syringomyelia, other therapeutic approaches (peripheral nerve root pain, nerve trunk pain and Sign Posterior Cord [SCI] pain). Material and Methods The methodology used, proposed by the French Society of Physical Medicine and Rehabilitation (SOFMER), includes a systematic review of the literature, the gathering of information regarding current clinical practices and a validation by a multidisciplinary panel of experts. Results Ninety-two articles were selected, 10 with a level of evidence at 2, 82 with a level of evidence at 4. Some articles lacked information on the type of injury, the pain characteristics and the symptoms’ evolution over time. Drez This type of procedure has been validated for its effectiveness on pain at the level of injury (transitional zone pain), but is inefficient for pain located below the level of injury. Posttraumatic syringomyelia (PTS): suspected when there is an increased neurological impairment, changes below the level of injury (mainly bladder dysfunctions) or a sudden onset of pain. The surgery associates arachnoid grafting, cyst drainage, expansile dural plasty (same treatment for posttraumatic tethered spinal cord and posttraumatic myelomalacia). Peripheral nerve root, nerve trunk or transitional zone pain Surgical implants (screws or clips) can generate radicular pain caused by inflammation and they can even move around with time. The material-induced constraints can also trigger pain. Surgical removal of osteosynthesis material (with an eventual saddle block) remains a simple procedure yielding good results. Correcting surgeries can also be performed (malunion and nonunion). Finally, compressive neuropathies (carpal tunnel syndrome, ulnar nerve entrapment) already have a well-defined treatment. Conclusion The literature review can define the relevance of surgical treatments on some types of SCI pain. However, the results of many articles are difficult to analyze, as they do not report clinical or follow-up data.

Histologic Features of Mesotherapy-induced Orbital Fat Inflammation

A 67-year-old man developed acute orbital inflammation after receiving cosmetic mesotherapy (Lipo-Dissolve) to the inferior orbital fat compartments. The injection was intended to cause lipolysis and shrinkage of fat lobules with subsequent cosmetic improvement. Injections of a mixture of bile salts, phospholipid, and alcohol preservative bilaterally in inferior orbital fat lobules led to an acute inflammatory reaction characterized histologically 12 days later by mild lymphocytic infiltration, fat necrosis, and fibrosis in the target areas. Benign proliferation of peripheral nerve trunks consistent with a traumatic neuroma was also noted histologically on one side. Inflammation including fat necrosis and traumatic neuroma are all possible consequences of mesotherapy.

Selective Vulnerability of Peripheral Nerves in Avian Riboflavin Deficiency Demyelinating Polyneuropathy

Riboflavin (vitamin B2) deficiency in young chickens produces a demyelinating peripheral neuropathy. In this study, day-old broiler meat chickens were fed a riboflavin-deficient diet (1.8 mg/kg) and killed on posthatch days 6, 11, 16, 21, and 31, while control chickens were given a conventional diet containing 5.0 mg/kg riboflavin. Pathologic changes were found in sciatic, cervical, and lumbar spinal nerves of riboflavin-deficient chickens from day 11 onwards, characterized by endoneurial oedema, hypertrophic Schwann cells, tomacula (redundant myelin swellings), demyelination/remyelination, lipid deposition, and fibroblastic onion bulb formation. Similar changes were also found in large and medium intramuscular nerves, although they were less severe in the latter. However, by contrast, ventral and dorsal spinal nerve roots, distal intramuscular nerves, and subcutaneous nerves were normal at all time points examined. These findings demonstrate, for the first time, that riboflavin deficiency in young, rapidly growing chickens produces selective injury to peripheral nerve trunks, with relative sparing of spinal nerve roots and distal nerve branches to muscle and skin. These novel findings suggest that the response of Schwann cells in peripheral nerves with riboflavin deficiency differs because either there are subsets of these cells in, or there is variability in access of nutrients to, different sites within the nerves.

Amelogenin in cranio‐facial development: the tooth as a model to study the role of amelogenin during embryogenesis

The amelogenins comprise 90% of the developing extracellular enamel matrix proteins and play a major role in the biomineralization and structural organization of enamel. Amelogenins were also detected, in smaller amounts, in postnatal calcifying mesenchymal tissues, and in several nonmineralizing tissues including brain. Low molecular mass amelogenin isoforms were suggested to have signaling activity; to produce ectopically chondrogenic and osteogenic-like tissue and to affect mouse tooth germ differentiation in vitro. Recently, some amelogenin isoforms were found to bind to the cell surface receptors; LAMP-1, LAMP-2 and CD63, and subsequently localize to the perinuclear region of the cell. The recombinant amelogenin protein (rHAM(+)) alone brought about regeneration of the tooth supporting tissues: cementum, periodontal ligament and alveolar bone, in the dog model, through recruitment of progenitor cells and mesenchymal stem cells. We show that amelogenin is expressed in various tissues of the developing mouse embryonic cranio-facial complex such as brain, eye, ganglia, peripheral nerve trunks, cartilage and bone, and is already expressed at E10.5 in the brain and eye, long before the initiation of tooth formation. Amelogenin protein expression was detected in the tooth germ (dental lamina) already at E13.5, much earlier than previously reported (E19). Application of amelogenin (rHAM(+)) beads together with DiI, on E13.5 and E14.5 embryonic mandibular mesenchyme and on embryonic tooth germ, revealed recruitment of mesenchymal cells. The present results indicate that amelogenin has an important role in many tissues of the cranio-facial complex during mouse embryonic development and differentiation, and might be a multifunctional protein.

In Vitro Magnetic Stimulation of Pig Phrenic Nerve With Transverse and Longitudinal Induced Electric Fields: Analysis of the Stimulation Site

The induced electric field transverse to peripheral nerve trunks has been shown to lead to stimulation, contrary to predictions of the cable equation. Two possible mechanisms of activation have been documented in literature: the change in the transmembrane voltage due to an electric field transverse to the membrane of a cylindrical fiber and the transverse field projection on the undulating fiber path within the fascicle. To distinguish between these alternatives, an analysis of the stimulation site was performed in vitro along 15 phrenic nerves from pigs, with a 5-cm-diameter round coil. Stimulation with induced electric field having longitudinal and attenuated transverse components resulted in stimulation sites in the vicinity of the negative peak of the spatial derivative of the longitudinal electric field and threshold variations with coil positions along the nerve trunk. Stimulation with a transverse field yielded patterns of one, two, or three stimulation sites, scattered or uniformly distributed around the location of the two field maxima. A nerve structure analysis outlined the fiber undulation within the fascicle and a network of wavy fascicles. The presence of this network and the variations of the stimulation site, and of the threshold suggest that the path of the fiber has a major undulation due to the undulation of the fascicles within the nerve trunk, which may be responsible for the stimulation with an electric field transverse to the nerve trunk.

Techniques of Peripheral Nerve Repair

Nerve injuries extend from simple nerve compression lesions to complete nerve injuries and severe lacerations of the nerve trunks. A specific problem is brachial plexus injuries where nerve roots can be ruptured, or even avulsed from the spinal cord, by traction. An early and correct diagnosis of a nerve injury is important. A thorough knowledge of the anatomy of the peripheral nerve trunk as well as of basic neurobiological alterations in neurons and Schwann cells induced by the injury are crucial for the surgeon in making adequate decisions on how to repair and reconstruct nerves. The technique of peripheral nerve repair includes four important steps (preparation of nerve end, approximation, coaptation and maintenance). Nerves are usually repaired primarily with sutures applied in the different tissue components, but various tubes are available. Nerve grafts and nerve transfers are alternatives when the injury induces a nerve defect. Timing of nerve repair is essential. An early repair is preferable since it is advantageous for neurobiological reasons. Postoperative rehabilitation, utilising the patients' own coping strategies, with evaluation of outcome are additional important steps in treatment of peripheral nerve injuries. in the rehabilitation phase adequate handling of pain, allodynia and cold intolerance are emphasised.

Decompression of peripheral nerve trunks in leprosy to prevent the development and progression of deformities

Background:Peripheral nerve involvement results in deformities in leprosy. High doses (40-60 mg) of steroids along with anti-leprosy drugs is the preferred treatment, even though 70-75% cases still develop deformity. Early surgical decompression of nerves gives better chances of preventing deformity. We have analyzed the role of early surgical decompression in such cases.Materials and Methods:Five hundred nerves (386 ulnar, 60 median and 54 posterior tibial) not responding to the medical treatment in 12 weeks, were undertaken for external and internal nerve trunk decompression. These cases were followed up for five to 20 years at various intervals.Results:The pain in nerve (neuralgia) recovered in all cases of ulnar, median and posterior tibial nerves. Full sensory recovery to pinprick and feather or cotton wool touch was seen in 50% cases of all the three nerves. Twenty percent cases maintained the preoperative levels of sensory status. Plantar ulcers healed within six months after decompression of posterior tibial nerve but six cases showed recurrence. Overall motor recovery in ulnar nerve was 89% and 70% in median nerve.Conclusions:The sensory recovery restores protective sensation which prevents secondary injuries. The improvement of motor power gives better function and improves the appearance, which in the absence of surgical intervention was not possible.

Morphological and Ultrastructural Analysis of the Watershed Zones After Stripping of the Vasa Nervorum

Peripheral nerve trunks are well-vascularized structures where a well-developed collateral system may compensate for local vascular damage. Vasculitis in nerve has a predilection for epineurial vessels and causes to the peripheral neuropathy, which is a major clinical feature of primary and secondary systemic vasculitides. In the present study, the goal was to simulate the vasculitic neuropathy in rat sciatic nerve and to investigate the watershed zones after stripping of the epineural vessels of the sciatic nerve. Sciatic function index values, light and electron microscopic evaluations of the experimental sciatic nerve suggested that the sciatic nerve was normal except for some watershed zones located in the peripheral part of the nerve. Although there is abundant collateral circulation in the peripheral nerve, distribution of the vessels of the watershed zones as observed in the present study should be elucidated by further studies.

RAGE, Diabetes, and the Nervous System

Longstanding diabetes mellitus targets kidney, retina, and blood vessels, but its impact upon the nervous system is another important source of disability. Diabetic peripheral neuropathy is a serious complication of inadequately treated diabetes leading to sensory loss, intractable neuropathic pain, loss of distal leg muscles, and impairment of balance and gait. Diabetes has been implicated as a cause of brain atrophy, white matter abnormalities, and cognitive impairment and a risk factor for dementia. Recent studies have incriminated advanced glycation end products (AGEs) and their receptor (RAGE) in the pathogenesis of diabetic nervous system complications. The availability of RAGE knockout mice and a competitive decoy for AGEs, soluble RAGE (sRAGE), has advanced our knowledge of the RAGE-mediated signalling pathways within the nervous system. They also provide hope for a future novel intervention for the prevention of diabetes-associated neurological complications. This review will discuss current knowledge of diabetes- and RAGE-mediated neurodegeneration, involving the distal-most level of epidermal nerve fibers in skin, major peripheral nerve trunks, dorsal root ganglia, spinal cord, and brain.

Prions in the peripheral nerves of bovine spongiform encephalopathy-affected cattle

With the use of increasingly sensitive methods for detection of the abnormal isoform of prion protein (PrP(Sc)) and infectivity in prion diseases, it has recently been shown that parts of the peripheral nervous system (PNS) of bovine spongiform encephalopathy (BSE)-affected cattle may become infected. It has been reported that prions spread to the central nervous system (CNS) via the PNS in sheep scrapie, but the pathogenesis of BSE in cattle is less well understood. To determine whether parts of the PNS other than those implicated directly in the hypothetical pathogenetic spread of agent from the intestine to the CNS become involved before or after the CNS is affected, PrP(Sc) distribution was investigated by a highly sensitive Western blotting technique in dorsal root ganglia, stellate ganglion, phrenic, radial and sciatic nerves, adrenal gland and CNS of cattle that were inoculated orally with BSE-affected brain and culled sequentially. In experimentally BSE-affected cattle, PrP(Sc) was first detected in the CNS and dorsal root ganglia; subsequently, PrP(Sc) accumulation was detected in the peripheral nerve trunks. PrP(Sc) was also detected in the adrenal glands of cattle that showed clinical signs. No PrP(Sc) was detected in the PNS of BSE-negative cattle. This study shows that, with respect to dorsal root ganglia, a paravertebral sympathetic ganglion and the somatic nerves examined, PrP(Sc) is detected in the PNS during the disease course at the same time as, or after, it accumulates in the CNS.

Implantation mechanics of tungsten microneedles into peripheral nerve trunks

50 microm tungsten microneedles have been used as a means to introduce longitudinal intra-fascicular electrodes (LIFE) into small peripheral nerve fascicles. However, recent attempts to implant LIFEs into larger, human sized nerves with the same needles resulted in buckling failure of the introducer needle. In the present study, the implantation mechanics (penetration forces and penetration dimple depth) of electrosharpened tungsten microneedles ranging in diameters from 50 to 200 microm into freshly excised porcine peripheral nerve trunks between 3 and 5 mm in thickness was characterized to understand the implantation mechanics and to find the minimum needle diameter that would result in successful penetration. The implant success rate was found to be highest with needles having diameters between 80 and 120 microm. The force of successful penetration ranged from 7.2 +/- 0.6 to 71.8 +/- 19.5 mN, and increased monotonically with needle diameter. It also had a tendency to increase with increasing tip angles. The dimple depth for successful penetrations varied between 1 and 1.5 mm, and also tended to increase with increasing tip angles, although it was generally not affected by increased needle diameter. Only the smallest penetration dimple depth was found to be different from the others and was associated with the smallest diameter needle (50 microm). Analysis based on the critical buckling force and the measured implantation forces indicated a 15 mm long needle of 80 microm diameter would be necessary and sufficient to penetrate medium to large sized nerves.

Regenerative failure of diabetic nerves bridging transection injuries

Failed regeneration compounds the deficits imposed by diabetes from peripheral neuropathy. In this work, we addressed how diabetes or local glucose toxicity might impact peripheral nerve trunk regeneration and reconstitution across major sciatic nerve transection injuries of rats. Specific conduits, amendable to manipulation of infused glucose concentrations through a T connection, were perfused with 5 or 30 mmol/L glucose in nondiabetics or 5 mmol/L glucose in rats with experimental diabetes. Quantitative early and later regenerative outgrowth was measured. Local glucose exposure had no impact on early axon or Schwann cell outgrowth or partnering nor later myelinated axon regeneration. Despite only mildly attenuated early sprouting of axons with Schwann cells, diabetic bridges exhibited massive later failure of reconstitution by 3 weeks after injury. Diabetes is associated with severe limitations in regenerative success, despite appropriate early axon outgrowth.

Early nerve damage in leprosy: An electrophysiological study of ulnar and median nerves in patients with and without clinical neural deficits

Peripheral nerve trunk involvement in leprosy is very common. However, by the time it becomes clinically manifest, the damage is quite advanced. If the preclinical nerve damage can be detected early, the deformities and disabilities can be prevented to a large extent. To assess the electrophysiological functions of the ulnar and median nerve trunks in cases of clinically manifest leprosy with and without manifest nerve damage at different durations of nerve damage. Electrophysiological functions of ulnar and median nerves were studied in leprosy patients, both normal and at different stages of disease and damage. PB cases, having disease for six months or less, without neurological symptoms and clinically normal appearing nerve. Mean was taken of different values. The changes in values of different parameters were expressed as percentage change with reference to the control values (increase or decrease). Reduced nerve conduction velocities and changes in latency and amplitude were observed. Changes in sensory nerve conduction were more pronounced. Sensory latencies and amplitude changes were more severe than motor latencies and amplitudes in cases with manifest muscle palsies. Changes in MB cases were less marked. Further studies are needed to identify parameters likely to be helpful in the diagnosis of early nerve damage.

Immune cell involvement in dorsal root ganglia and spinal cord after chronic constriction or transection of the rat sciatic nerve

Chronic constriction injury (CCI) of the sciatic nerve in rodents produces mechanical and thermal hyperalgesia and is a common model of neuropathic pain. Here we compare the inflammatory responses in L4/5 dorsal root ganglia (DRGs) and spinal segments after CCI with those after transection and ligation at the same site. Expression of ATF3 after one week implied that 75% of sensory and 100% of motor neurones had been axotomized after CCI. Macrophage invasion of DRGs and microglial and astrocytic activation in the spinal cord were qualitatively similar but quantitatively distinct between the lesions. The macrophage and glial reactions around neurone somata in DRGs and ventral horn were slightly greater after transection than CCI while, in the dorsal horn, microglial activation (using markers OX-42(for CD11b) and ED1(for CD68)) was greater after CCI. In DRGs, macrophages positive for OX-42(CD11b), CD4, MHC II and ED1(CD68) more frequently formed perineuronal rings beneath the glial sheath of ATF3+ medium to large neurone somata after CCI. There were more invading MHC II+ macrophages lacking OX-42(CD11b)/CD4/ED1(CD68) after transection. MHC I was expressed in DRGs and in spinal sciatic territories to a similar extent after both lesions. CD8+ T-lymphocytes aggregated to a greater extent both in DRGs and the dorsal horn after CCI, but in the ventral horn after transection. This occurred mainly by migration, additional T-cells being recruited only after CCI. Some of these were probably CD4+. It appears that inflammation of the peripheral nerve trunk after CCI triggers an adaptive immune response not seen after axotomy.

Hereditary Neuropathy With Liability to Pressure Palsies Manifesting By Recurrent Neuropathic Pain

Abstract Hereditary neuropathy with liability to pressure palsies is an autosomal dominant disease that presents with focal neurological deficits in the territory of peripheral nerves. The usual cause is a deletion of 1.5 Mb at chromosome 17p11.2. It has been clear from several clinical series that other phenotypes, such as isolated sensory deficits, chronic mononeuropathies, motor sensory neuropathies like CMT1A, polyneuropathy like CIDP, and Davidenkow's syndrome, may also occur in affected families. In this report, the authors present a new family with hereditary neuropathy with liability to pressure palsies (HNPP) in which one of the members suffered recurrent episodes of pain in the territory of peripheral nerve trunks along with generalized conduction nerve abnormalities and the common deletion of 1.5 Mb at 17p12.1. On this basis, the authors propose that HNPP should be considered in the differential diagnosis of painful multiple mononeuropathy.

Kinetics of ATP release following compression injury of a peripheral nerve trunk

Compression and/or contusion of a peripheral nerve trunk can result in painful sensations. It is possible that release of ATP into the extracellular space may contribute to this symptom. In the present study, we used real-time measurements of ATP-induced bioluminescence together with electrophysiological recordings of compound action potentials to follow changes in the extracellular ATP concentration of isolated rat spinal roots exposed to mechanical stimuli. Nerve compression for about 8 s resulted in an immediate release of ATP into the extracellular space and in a decrease in the amplitude of compound action potentials. On average, a rise in ATP to 60 nM was observed when nerve compression blocked 50% of the myelinated axons. After the compression, the extracellular concentration of ATP returned to the resting level within a few minutes. The importance of ecto-nucleotidases for the recovery period was determined by exposure of isolated spinal roots to high concentrations of ATP and by use of inhibitors of ecto-nucleotidases. It was observed that spinal roots have a high capacity for ATP hydrolysis which is only partially blocked by βγ-methylene ATP and ARL 67156. In conclusion, acute nerve compression produces an increase in the extracellular concentration of ATP and of its metabolites which may be sufficient for activation of purinergic P2 and/or P1 receptors on axons of nociceptive afferent neurons.

Management of peripheral neuropathic pain: Integrating neurobiology, neurodynamics, and clinical evidence

Peripheral neuropathic pain is the term used to describe situations where nerve roots or peripheral nerve trunks have been injured by mechanical and/or chemical stimuli that exceeded the physical capabilities of the nervous system. Clinical manifestations of peripheral neuropathic pain are often discussed in terms of positive and negative symptoms. Positive symptoms reflect an abnormal level of excitability in the nervous system and include pain, paresthesia, dysesthesia, and spasm. Negative symptoms indicate reduced impulse conduction in the neural tissues and include hypoesthesia or anesthesia and weakness. It is proposed that conservative management incorporating neurodynamic and neurobiology education, nonneural tissue interventions, and neurodynamic mobilization techniques can be effective in addressing musculoskeletal presentations of peripheral neuropathic pain. While a small amount of clinical evidence lends some support to this proposal, much more clinical research is necessary to identify those patients with peripheral neuropathic pain that will respond most favorably to neurodynamic mobilization techniques and clarify specific treatment parameters that will be most effective. Regardless of the results of this future research, conservative care will always need to be based on sound clinical reasoning so that interventions can be individualized to address the nuances of each patient's presentation of peripheral neuropathic pain.

End-to-side nerve repair induces nuclear translocation of activating transcription factor 3

We wanted to find out if any of three different types of manipulations: a piece of muscle or nerve put parallel to a nerve; an epineurial window made, or sutures inserted into a nerve, or both; or pieces of nerve sutured to an epineurial window end-to-side to the musculocutaneous or sciatic nerve, resulted in activation of activating transcription factor 3 (ATF3) in neurons and in non-neuronal cells. ATF3, a marker of cell activation, was investigated by immunocytochemistry one week after manipulation. A piece of nerve or muscle parallel to a nerve did not induce ATF3 locally in the nerve and induced ATF3 only rarely in neurons. In contrast, an epineurial window or insertion of sutures, or both, with or without attachment of a piece of nerve placed end-to-side, induced robust ATF3 expression. We conclude that an injury to a peripheral nerve trunk associated with end-to-side nerve repair, activates neurons and non-neuronal cells and may contribute to sprouting of axons into the nerve attached end-to-side.

The INFIR Cohort Study: investigating prediction, detection and pathogenesis of neuropathy and reactions in leprosy. Methods and baseline results of a cohort of multibacillary leprosy patients in North India

The aim of this study was to find predictors of neuropathy and reactions, determine the most sensitive methods for detecting peripheral neuropathy, study the pathogenesis of neuropathy and reactions and create a bank of specimen, backed up by detailed clinical documentation. A multi-centre cohort study of 303 multibacillary leprosy patients in Northern India was followed for 2 years. All newly registered MB patients requiring a full course of MDT, who were smear positive and/or had six or more skin lesions and/or had two or more nerve trunks involved, were eligible. A detailed history was taken and physical and neurological examinations were performed. Nerve function was assessed at each visit with nerve conduction testing, warm and cold detection thresholds, vibrometry, dynamometry, monofilaments and voluntary muscle testing. Because the latter two are widely used in leprosy clinics, they were used as 'gold standard' for sensory and motor impairment. Other outcome events were type 1 and 2 reactions and neuritis. All subjects had a skin biopsy at registration, repeated at the time of an outcome event, along with a nerve biopsy. These were examined using a variety of immunohistological techniques. Blood sampling for serological testing was done at every 4-weekly clinic visit. At diagnosis, 115 patients had an outcome event of recent onset. Many people had skin lesions overlying a major nerve trunk, which were shown to be significantly associated with an increased of sensory or motor impairment. The most important adjusted odds ratios for motor impairment were, facial 4.5 (1.3-16) and ulnar 3.5 (1.0-8.5); for sensory impairment they were, ulnar 2.9 (1.3-6.5), median 3.6 (1.1-12) and posterior tibial 4.0 (1.8-8.7). Nerve enlargement was found in 94% of patients, while only 24% and 3% had paraesthesia and nerve tenderness on palpation, respectively. These increased the risk of reactions only marginally. Seven subjects had abnormal tendon reflexes and seven abnormal joint position sense. In all but one case, these impairments were accompanied by abnormalities in two or more other nerve function tests and thus seemed to indicate more severe neuropathy. At diagnosis, 38% of a cohort of newly diagnosed MB leprosy patients had recent or new reactions or nerve damage at the time of intake into the study. The main risk factor for neuropathy found in this baseline analysis was the presence of skin lesions overlying nerve trunks. They increased the risk of sensory or motor impairment in the concerned nerve by 3-4 times. For some nerves, reactional signs in the lesions further increased this risk to 6-8 times the risk of those without such lesions. Patients with skin lesions overlying peripheral nerve trunks should be carefully monitored for development of sensory or motor impairment.

262 TISSUE-SPECIFIC ANALYSIS OF PRION EXPRESSION IN EARLY BOVINE FETUSES

The prion protein (PrP) is best known for its mis-folded, pathogenic isoform, which is widely regarded as the infectious agent in transmissable spongiform encephalopathies. However, the role of normal, cellular PrP, a host-encoded 29-kD glycoprotein tethered to the cell membrane by a phosphatidyl-inositol glycane (GPI) anchor, is poorly understood. PrP binds copper with high affinity, has antioxidant activity and may play a role in cell adhesion and/or signaling. PrP is expressed in mouse embryos on 6.5 days post-coitum in extra-embryonic tissue and at 13.5 days in the central and peripheral nervous system, intestine, and dental lamina. Our previous data revealed PrP gene expression in bovine embryos throughout pre-implantation embryo development. As part of a larger effort to map the ontogeny of cellular PrP expression in cattle, we sought here to analyze in early bovine fetuses (1) total PrP gene expression by real-time quantitative PCR (QPCR), and (2) tissue-specific PrP expression by immunohistochemistry. Fetuses were obtained from donor cattle bred by artificial insemination (AI; Day 0) and subjected to mid-ventral laparotomy on Days 32 (n = 2) and 39 (n = 2). Immediately upon recovery, one fetus from each stage was placed in RNAlater for RNA isolation and the other fixed in 10% formalin for immunohistochemistry. RNA was isolated using an RNeasy� mini kit (Qiagen, Valencia, CA, USA). cDNA was generated by reverse transcription with random hexamer priming and used the ΔΔcT method for estimation of PrP expression by QPCR. Tissue-specific expression was determined by immunohistochemistry. Formalin-fixed fetuses were embedded in paraffin, sagittally sectioned, dehydrated, and subjected to an unmasking protocol that employed Vectorlab unmasking solution and autoclaving. Tissues were then probed with a primary anti-PrP monoclonal antibody (SAF 32; Cayman Chemical Company, Ann Arbor, MI, USA). Bound primary antibody was detected with a biotinylated horse anti-mouse secondary antibody complexed to horseradish peroxidase using the ABC kit (Vector Laboratories, Burlingame, CA, USA). Probed sections were then counterstained with hematoxolin and eosin. Neighboring sections, processed identically but to which no primary antibody was added, served as controls. PrP gene expression was detected by QPCR at both stages examined and tended to be higher in Day 39 compared to Day 32 fetuses. PrP immunoreactivity was found throughout the central and peripheral nervous systems, ganglia, nerve trunks, and neural cell populations of sensory organs in both Day 32 and Day 39 fetuses. PrP immunolabeling was also observed in the mesonephric kidney, liver, and heart in the Day 39 fetus. At both stages, immunoreactivity was most intense in the nervous system. Thus, PrP is expressed in a tissue-specific pattern in early bovine fetuses. Tissue distribution of fetal PrP expression appears similar to that of adult PrP. Moreover, PrP appears to be expressed in a developmentally regulated fashion in some tissues.