Nerve Compartment Research Articles

Optic Nerve Compartment Syndrome in a Patient with Optic Nerve Sheath Meningioma

To report a patient with optic nerve (ON) sheath meningioma, unilateral optic disc swelling, and inhomogeneous cerebrospinal fluid (CSF) composition between lumbar CSF and CSF from the subarachnoid space (SAS) of the affected ON. A 39-year-old woman presented with unilateral optic disc swelling and slight deterioration of visual function in the left eye. Extensive laboratory workup and magnetic resonance imaging (MRI) of the brain and orbits were performed. As radiotherapy was refused by the patient, ON sheath fenestration (ONSF) was offered and performed in order to stop deterioration. CSF from the SAS of the ON was sampled. Laboratory workup was within normal limits. MRI of the left orbit demonstrated enhancement of the dura in the precanalicular portion of the ON and distension of the SAS, most prominent in the bulbar portion of the ON. On lumbar puncture the opening pressure measured 19 (cm H2O). Compared to the lumbar CSF the CSF of the affected ON SAS showed markedly elevated measurements for albumin, IgG, and beta-trace protein. Visual function remained stable over a follow-up time of 18 months. Composition of CSF is considered to be homogenous throughout all CSF spaces. In this patient the authors found a marked concentration-gradient of albumin, IgG, and beta-trace protein between the CSF in the spinal canal and the CSF in the SAS of the affected ON. Based on the radiologic features of the left ON and the dissociated beta-trace protein concentrations in the CSF of the SAS of the ON and the lumbar CSF, the diagnosis of an ON sheath compartment syndrome due to an ON sheath meningioma was made.

Cerebrospinal fluid dynamics between the intracranial and the subarachnoid space of the optic nerve. Is it always bidirectional?

CSF is thought to flow continuously from the site of production in the ventricles into interconnected spaces; i.e. cisterns and subarachnoid spaces (SASs). Since the SAS of the optic nerve is defined by a cul-de-sac anatomy, it is not evident how local CSF might recycle from that region to the general SAS. The concept of free communication of CSF has recently been challenged by the description of a concentration gradient of beta-trace protein, a lipocalin-like prostaglandin d-synthase (L-PGDS), between the spinal CSF and that in the SAS of the optic nerve, indicating diminished local clearance or local overproduction of L-PGDS here. In fact, computed cisternography with a contrast agent in three patients with idiopathic intracranial hypertension and asymmetric papilloedema demonstrate a lack of contrast-loaded CSF in the SAS of the optic nerve despite it being present in the intracranial SAS, thus suggesting compartmentation of the SAS of the optic nerve. The concept of an optic nerve compartment syndrome is further supported by a concentration gradient of brain-derived L-PGDS between the spinal CSF and the CSF from the optic nerve SAS in the same patients.

Combined psoas compartment and sciatic nerve block: efficacy and complications assessment

Combined psoas compartment and sciatic nerve block: efficacy and complications assessment

Psoas compartment and sciatic nerve block without general anesthesia for total knee joint replacement- is it reliable?

Psoas compartment and sciatic nerve block without general anesthesia for total knee joint replacement- is it reliable?

Intraoperative validation of CT-based lymph nodal levels, sublevels IIa and IIb: Is it of clinical relevance in selective radiation therapy?

The objectives of this study are to discuss the intraoperative validation of CT-based boundaries of lymph nodal levels in the neck, and in particular the clinical relevance of the delineation of sublevels IIa and IIb in case of selective radiation therapy (RT). To validate the radiologically defined level contours, clips were positioned intraoperatively at the level boundaries defined by surgical anatomy. In 10 consecutive patients, clips were placed, at the time of a neck dissection being performed, at the most cranial border of the neck. Anterior-posterior and lateral X-ray films were obtained intraoperatively. Next, in 3 patients, neck levels were contoured on preoperative contrast-enhanced CT scans according to the international consensus guidelines. From each of these 3 patients, an intraoperative CT scan was also obtained, with clips placed at the surgical-anatomy-based level boundaries. The preoperative (CT-based) and intraoperative (surgery-defined) CT scans were matched. Clips placed at the most cranial part of the neck lined up at the caudal part of the transverse process of the cervical vertebra C-I. The posterior border of surgical level IIa (spinal accessory nerve [SAN]) did not match with the posterior border of CT-based level IIa (internal jugular vein [IJV]). Other surgical boundaries and CT-based contours were in good agreement. The cranial border of the neck, i.e., the cranial border of level IIa/IIb, corresponds to the caudal edge of the lateral process of C-I. Except for the posterior border between level IIa and level IIb, a perfect match was observed between the other surgical-clip-identified levels II-V boundaries (surgical-anatomy) and the CT-based delineation contours. It is argued that (1) because of the parotid gland overlapping part of level II, and (2) the frequent infestation of occult metastatic cells in the lymph channels around the IJV, the division of level II into radiologic sublevels IIa and IIb may not be relevant. Sparing of, for example, the ipsilateral parotid gland in selective RT can even be a treacherous undertaking with respect to regional tumor control. In contrast, the surgeon's reasoning for preserving the surgical sublevel IIb is that the morbidity associated with dissection of the supraspinal accessory nerve compartment of level II is reduced, whereas there is evidence from the surgical literature that no extra risk for regional tumor control is observed. Therefore, in selective neck dissections, the division into surgical sublevels IIa/IIb makes sense.

Transient expression of hypoxia-inducible factor-1 alpha and target genes in peripheral nerves from diabetic rats

Decreased blood flow is one of the earliest physiological changes observed after the onset of either clinical or experimental diabetes. The reduction in blood flow is believed to lead to nerve hypoxia, which in conjunction with other metabolic alterations and degenerative processes in different nerve compartments, results in the dysfunction known as diabetic neuropathy. The transcriptional regulator hypoxia-inducible factor-1 alpha (HIF-1α) accumulates rapidly under hypoxic conditions and modulates the expression of several target genes that protect tissues against ischemia and infarction. At present it is unclear whether diabetic nerve injury results from an abnormal response of HIF-1α and its protective target genes. In the present study we have analyzed the expression and activity of HIF-1α and its target genes in diabetic nerves as a first step to determine their possible contribution to the development or maintenance of diabetic neuropathy. We observed a transient increase in the expression of HIF-1α that peaked between 4 and 6 weeks and declined 8 weeks after induction of experimental diabetes in rats. The increase in HIF-1α in diabetic nerves coincided with a similarly transient increase in the expression of several HIF-1α target genes including vascular endothelial growth factor, lactate dehydrogenase and erythropoietin, which subsided 8–10 weeks after induction of diabetes. These results suggest that the transient activation of neurotrophic and angiogenic genes, as opposed to a more sustained effect in response to the chronic injury, may be responsible for the alterations in nerve function and regeneration that characterize the diabetic neuropathy.

Vascular endothelial growth factor controls neuronal migration and cooperates with Sema3A to pattern distinct compartments of the facial nerve

Developing neurons accurately position their somata within the neural tube to make contact with appropriate neighbors and project axons to their preferred targets. Taking advantage of a collection of genetically engineered mouse mutants, we now demonstrate that the behavior of somata and axons of the facial nerve is regulated independently by two secreted ligands for the transmembrane receptor neuropilin 1 (Nrp1), the semaphorin Sema3A and the VEGF164 isoform of Vascular Endothelial Growth Factor. Although Sema3A is known to control the guidance of facial nerve axons, we now show that it is not required for the pathfinding of their somata. Vice versa, we find that VEGF164 is not required for axon guidance of facial motor neurons, but is essential for the correct migration of their somata. These observations demonstrate, for the first time, that VEGF contributes to neuronal patterning in vivo, and that different compartments of one cell can be co-ordinately patterned by structurally distinct ligands for a shared receptor.

Complement factors in adult peripheral nerve: a potential role in energy metabolism

Complement cascade factors are known to play a critical role in myelin clearance after peripheral nerve injury. Here we show that components of both the classical ( C1qa, C1qb, C1qc, C2 and C4) and alternative ( C3, B and adipsin) pathways are expressed by uninjured peripheral nerve as well. mRNAs of components of the alternative pathway were predominantly found in the peri/epineurium, although factor C3 and factor B were also detected in the endoneurial compartment of adult nerve. Interestingly, adipsin mRNA was detected only in peri/epineurium, while adipsin protein was present in both peri/epineurium and endoneurium. This suggests that adipsin is transported to the endoneurium via the circulation from the peri/epineurium or outside of the nerve. Factor 5 and factor 9, necessary for the formation of the membrane–attack complex, were not detected in any part of the healthy peripheral nerve, which together with the observed presence of negative regulators of complement activation, is likely to prevent damage to the healthy nerve caused by complement activation. By analogy with the known role of complement factors in fat, we propose that local expression of these factors plays a role in the regulation of fatty acid homeostasis in the nerve and, thereby, in energy metabolism cross-talk between different compartments of the peripheral nerve.

1P-0232 Apolipoprotein A-I-mediated secretion of apolipoprotein E has structural requirements distinct from those related to stimulation of cholesterol efflux

Our previous work demonstrated that the sterol response element binding proteins (SREBP)-1 and SREBP-2, which are the key regulators of storage lipid and cholesterol metabolism respectively, are highly expressed in Schwann cells of adult peripheral nerves. In order to evaluate the role of Schwann cell SREBPs in myelination and functioning of peripheral nerves we have determined their expression during development, after fasting and refeeding, and in a rodent model of diabetes. Our results show that SREBP-1c and SREBP-2, unlike SREBP-1a, are the major forms of SREBPs present in peripheral nerves. The expression profile of SREBP-2 follows the expression of genes involved in cholesterol biosynthesis, while SREBP-1c is co-expressed with genes involved in storage lipid metabolism. In addition, the expression of SREBP-1c in the endoneurial compartment of peripheral nerves depends on nutritional status and is disturbed in type 1 diabetes. In line with this, insulin elevates the expression of SREBP-1c in primary cultured Schwann cells by activating the SREBP-1c promoter. Taken together, these findings reveal that SREBP-1c expression in Schwann cells responds to metabolic stimuli including insulin and that this response is affected in type 1 diabetes mellitus. This suggests that disturbed SREBP-1c regulated lipid metabolism may contribute to the pathophysiology of diabetic peripheral neuropathy.

Peripheral neuropathies and anti-glycolipid antibodies.

This review charts the progress of anti-glycolipid antibodies in neuropathy, from their original discovery 20 years ago in immunoglobulin M paraproteinaemic neuropathy through to current discoveries mapping their relationship to subtypes of Guillain-Barré syndrome. Antibodies to >20 different glycolipids have now been associated with a wide range of clinically identifiable acute and chronic neuropathy syndromes. Particular progress has been achieved in understanding the link between acute motor axonal neuropathy and antibodies to GM1, GD1a, GM1b and GalNAc-GD1a, and between the cranial, bulbar and sensory variants of GBS and antibodies to the disialylated gangliosides GQ1b, GT1a, GD1b and GD3. In addition to clinical and serological studies, the origins and measurement of anti-glycolipid antibodies and their relationships to similar carbohydrate structures on infectious organisms, particularly Campylobacter jejuni, are discussed in the context of a molecular mimicry hypothesis. The structure and nomenclature of relevant glycolipids are outlined, along with information on their localization in nerve, and the influence this has on clinical phenotypes. Major advances have been made in animal modelling of anti-glycolipid antibody-associated diseases, both in vitro and in vivo. This has advanced our understanding of the role of anti-GQ1b antibodies in Miller Fisher syndrome with particular respect to the motor nerve terminal as a potential site of injury, and led to the creation of rabbit models of anti-GD1b and anti-GM1 antibody-mediated sensory and motor neuropathy, respectively. With such information in place, it will now be possible to determine the precise mechanisms by which antibodies injure the different compartments of peripheral nerve and establish how a range of immunomodulating therapies, including current treatments, exert their therapeutic effects. Despite these very significant advances, considerable gaps in our knowledge persist, and it is likely that other pathogenic pathways operate in inflammatory neuropathy that are unrelated to glycolipid antibodies, although these are outside the scope of this review.

Multiquantum filters and order in tissues.

In ordered systems, where the molecular motion is anisotropic, quadrupolar and dipolar interactions are not averaged to zero. In such cases, double quantum (DQ) coherences can be formed. This review deals mainly with the effect of anisotropic motion of water molecules and sodium ions in intact biological tissues on (2)H, (1)H and (23)Na NMR spectroscopy and its application to NMR imaging (MRI). Double quantum filtered (DQF) spectra of water molecules and sodium ions were detected in a variety of ordered biological tissues. In collagen-containing tissues such as ligaments, tendons, cartilage, skin, blood vessels and nerves, the DQ coherences are formed as a result of the interaction with the collagen fibers. In red blood cells and presumably also in nerve axons it stems from the interaction with the cytoskeleton. For (23)Na, an I = 3/2 nucleus, the DQ coherences can also be formed in isotropic media. By a judicial choice of the pulse angle in the DQ pulse sequence only the DQ coherences arising from anisotropic motion are detected. For I = 1 nuclei such as 2H, DQF spectra can be observed only in ordered structures. Thus, the observation of 2H DQF spectra is an indication of order. The same is true for pairs of equivalent 1H nuclei. The dependence of the DQF signal on the creation time of the double quantum coherences is characteristic to each tissue and allows signals to be resolved from different tissues by performing the measurements at different creation times. In this way, the 2H DQF signals of the different compartments of sciatic nerve were resolved and water diffusion in each compartment was studied independently. In the axon, the diffusion was heavily restricted perpendicular to the axon's long axis, a result from which the axon diameter could be deduced. In blood vessel walls, this characteristic enabled the different layers of the vessel to be viewed and studied under strain. For 2H, a DQF spectroscopic imaging sequence was used to study the orientation of the collagen fibers in the different zones of articular cartilage and bone plug. The effect of pressure on the fibers and their return to equilibrium was studied as well. In blood vessels, a DQF image was obtained and strain maps of the different layers were calculated. The efficiency of the 1H DQF imaging technique was demonstrated on a phantom of rat tail where only the four tendons were detected at short creation times. 1H DQF imaging and spectroscopy followed the healing of a rabbit's ruptured Achilles tendon and the results were far more sensitive to the process than conventional imaging. Finally, the method was implemented on a commercial whole body MRI spectrometer. Images of human wrist and ankle showed a positive contrast for the tendons and ligaments, indicating the potential of the method for clinical imaging. (c) 2001 John Wiley & Sons, Ltd.

Anisotropic and restricted diffusion of water in the sciatic nerve: A 2H double‐quantum‐filtered NMR study

The signals of water in the different compartments of rat sciatic nerve are resolved in the 2H double-quantum-filtered NMR spectrum, due to their different quadrupolar splittings and relaxation rates. This resolution allowed the independent measurement of the water diffusion coefficients in the different compartments. The water diffusion in all three compartments, the endoneurium, the epineurium and the axon was found to be anisotropic. Parallel to the nerve fiber the average intraxonal water diffusion coefficient was 1.11 × 10−5 cm2/sec, while in the perpendicular direction the diffusion is heavily restricted. The average perpendicular diffusion coefficient ranged from 0.29 × 10−5 cm2/sec to 0.05 × 10−5 cm2/sec for diffusion times of 7 msec and 50 msec, respectively. Assuming restricted diffusion in nonpermeable cylinders, intra-axonal mean diameters of 6.0, 7.4 and 9.0 μm were obtained for nerves taken from three different rats. Magn Reson Med 42:461–466, 1999. © 1999 Wiley-Liss, Inc.

Anisotropic and restricted diffusion of water in the sciatic nerve: A (2)H double-quantum-filtered NMR study.

The signals of water in the different compartments of rat sciatic nerve are resolved in the (2)H double-quantum-filtered NMR spectrum, due to their different quadrupolar splittings and relaxation rates. This resolution allowed the independent measurement of the water diffusion coefficients in the different compartments. The water diffusion in all three compartments, the endoneurium, the epineurium and the axon was found to be anisotropic. Parallel to the nerve fiber the average intraxonal water diffusion coefficient was 1.11 x 10(-5) cm(2)/sec, while in the perpendicular direction the diffusion is heavily restricted. The average perpendicular diffusion coefficient ranged from 0.29 x 10(-5) cm(2)/sec to 0.05 x 10(-5) cm(2)/sec for diffusion times of 7 msec and 50 msec, respectively. Assuming restricted diffusion in nonpermeable cylinders, intra-axonal mean diameters of 6.0, 7.4 and 9.0 microm were obtained for nerves taken from three different rats. Magn Reson Med 42:461-466, 1999.

Multi-component T1 relaxation and magnetisation transfer in peripheral nerve

We report here a study of longitudinal relaxation ( T 1) and magnetisation transfer (MT) in peripheral nerve. Amphibian sciatic nerve was maintained in vitro and studied at a magnetic field strength of 3 T. A CPMG pulse sequence was modified to include either a saturation pulse to measure T 1 relaxation or an off-resonance RF irradiation pulse to measure MT. The resulting transverse relaxation ( T 2) spectra yielded four components corresponding to three nerve compartments, taken to result from myelinic, axonal, and inter-axonal water, and a fourth corresponding to the buffer solution water in which the nerve sample was bathed. Each nerve component was analysed for T 1 relaxation and MT. All three nerve T 2 components exhibited unique T 1 relaxation and MT characteristics, providing further support for the assignment of the components to unique physical compartments of water. Numerical investigation of T 1sat measurements of each of the three nerve T 2 components indicates that while the two shorter-lived exhibit similar steady-state magnetisation transfer ratios ( MTRs), their respective MT properties are quite different. Simulations demonstrate that mobile water exchange between these two components is not necessary to explain their similar steady-state MTR. In the context of the assignment of these two components to signal from myelinic and axonal water, this is to say that these two microanatomical regions of nerve may exhibit similar steady-state MTR characteristics despite possessing widely different MT exchange rates. Therefore, interpreting changes in MTR solely to reflect a change in degree of myelination could lead to erroneous conclusions.

Single corrective osteotomy after knee para-articular fractures

Post-traumatic malalignment can occur on one or several planes following fractures in close proximity to the knee joint. In a clinical and radiological analysis of deformities, the frontal, sagittal and longitudinal alignment, as well as differences in femoral or tibial length and torsion, must be taken into account. The location of the correctional osteotomy is usually defined by the center of the angular and torsional deformity. Of decisive importance when choosing the site of the osteotomy are the local quality of bone and the soft tissue envelope, the condition of the articular cartilage in the different compartments of the knee, the stability of ligamentocapsular structures and preexistent deformities of the distal femur and proximal tibia. Therefore, the location of correctional osteotomies must be modified, depending on the individual situation. The appropriate approach and technique must be chosen from the different available operative techniques. Inaccurate planning and inappropriate operative techniques pose severe risks. Specific postoperative complications are compartment syndromes, nerve irritation and infection.

Treatment of adolescent Blount's disease using the ilizarov technique

The cause of adolescent Blount's disease is obscure, but the disorder is often associated with obesity. The treatment of the resultant varus deformity of the limb may also involve equalization of limb lenghts as well as addressing any existing femoral deformity. The Ilizarov technique is ideally suited for correction of deformity as well as lengthening if required. It allows adjustment of limb alignment in the postoperative period, if necessary, to achieve a perfect mechanical axis. Fixation of the tibia is achieved through four proximal and four distal wires affixed to rings and tensioned. Half pin modifications may also be used. Our series of Blount's corrections in 14 limbs achieved restoration of length and alignment in all cases with an average treatment time of 10 weeks. As opposed to reports of other techniques, there were no nerve palsies or compartment syndromes in these patients. The only complications were pin site infection and repeat osteotomy due to premature healing in one patient.

Identification of G Protein Subtypes in Peripheral Nerve and Cultured Schwann Cells

In this study, we investigated the expression of various G proteins in whole sciatic nerves, in myelin and nonmyelin fractions from these nerves, and in membranes of immortalized Schwann cells. In myelin, nonmyelin, and Schwann cell membranes we detected two 39-40-kDa pertussis toxin substrates that were resolved on separation on urea-gradient gels. Two cholera toxin substrates with apparent molecular masses of 42 and 47 kDa were present in nerve and brain myelin and in Schwann cell membranes. In these membranes, a third 45-kDa cholera toxin substrate, which displayed the highest labeling, was also present. Immunoblotting with specific antisera allowed the identification of G(o) alpha, Gi1 alpha, Gi2 alpha, Gi3 alpha, Gq/G11 alpha, and the two isoforms of Gs alpha in nerve homogenates, nerve, and brain myelin fractions. In Schwann cell membranes we identified G(o) alpha, Gi2 alpha, Gi3 alpha, and proteins from the Gq family, but no immunoreactivity toward anti-Gi1 alpha antiserum was detected. In these membranes, anti-Gs alpha antibody recognized the three cholera toxin substrates mentioned above, with the 45-kDa band displaying the highest immunoreactivity. Relative to sciatic nerve myelin, the Schwann cell membranes revealed a significantly higher expression of Gi3 alpha and the absence of Gi1 alpha. The different distribution of G proteins among the different nerve compartments might reflect the very specialized function of Schwann cells and myelin within the nerve.

Expression of the pro-opiomelanocortin gene in dorsal root ganglia, spinal cord and sciatic nerve after sciatic nerve crush in the rat

Neuropeptides related to α-melanocyte-stimulating hormone (α-MSH) stimulate nerve outgrowth following peripheral nerve injury and may play an important physiological role in peripheral nerve regeration. The mechanism of action underlying the neurotrophic effect of pharmacologically administered α-MSH is unknown. Here we investigate the hypothesis that reexpression of the proopiomelanocortin (POMC) gene, the prohormone of α-MSH/adrenocorticotropic hormone (ACTH)-like peptides, is part of the endogenous repertoire of peripheral nerve responses following injury. The effect of sciatic nerve crush on the expression of POMC mRNA between 0.5 h and 14 days after crush was investigated using polymerase chain reaction (PCR) and Northern blot analysis. The presence of a POMC transcript in dorsal root ganglia (DRG), spinal cord and in the sciatic nerve at the crush site could be demonstrated in both control and lesioned animals by PCR using primers located in exon 1 and 3 of the POMC gene. Minute quantities of two POMC transcripts (1200 nt and 800 nt) could be detected by Northern blot analysis of total RNA prepared from DRG, spinal cord and the sciatic nerve of control animals and of animals subjected to nerve crush. POMC mRNA expression was, however, not increased following nerve crush. Probes specific for exons 1 and 2 or specific for exon 3 of the POMC gene were employed to demonstrate that the 800 nt transcript represents the truncated POMC mRNA previously shown to be present in extra-pituitary tissue. The larger 1200 nt transcript comigrates with the full length POMC mRNA expressed in the pituitary gland. The present results demonstrate the expression of small amounts of POMC mRNA in all compartments of the sciatic nerve. The absence of an induction of POMC expression in response to nerve crush suggests that the stimulating effect of exogenously applied α-MSH does not mimic a POMC derived neurotrophic peptide induced in the nerve following nerve injury

Plasticity of integrin expression by nerve-derived connective tissue cells. Human Schwann cells, perineurial cells, and fibroblasts express markedly different patterns of beta 1 integrins during nerve development, neoplasia, and in vitro.

Strikingly selective expression patterns of beta 1, alpha 2, alpha 3, and alpha 5 integrin subunits were revealed in endoneurium, perineurium, and epineurium of fetal and adult human peripheral nerve by immunostaining with specific antibodies. The alpha 2 subunit was expressed only on Schwann cells both in fetal and adult nerve, whereas the alpha 3 epitopes were expressed exclusively in the adult tissue and were primarily present on perineurial cells. The alpha 5 epitopes were expressed only on the innermost cell layer of perineurium of fetal and adult nerve. The tumor cells within schwannomas and cutaneous neurofibromas expressed both alpha 2 and alpha 3 subunits, indicating that Schwann cells have the potential to express also the alpha 3 subunit in vivo. Cell cultures established from human fetal nerve and neurofibromas revealed expression of the alpha 2 and alpha 5 epitopes on Schwann cells, perineurial cells, and fibroblasts, whereas only Schwann cells contained the alpha 3 epitopes which were occasionally concentrated on the adjacent Schwann cells at cell-cell contacts. Our findings emphasize that nerve connective tissue cells change their profiles for expression of extracellular matrix receptors under conditions which have different regulatory control signals exerted by, for example, axons, humoral factors, or the extracellular matrix of the peripheral nerve. This plasticity may play an important role during nerve development and in neoplastic processes affecting the connective tissue compartments of peripheral nerve.

Partial pressure of oxygen in brain and peripheral nerve during damaging electrical stimulation

The studies were performed to elucidate the mechanism underlying the neural damage which may occur during prolonged electrical stimulation of either brain tissue or peripheral nerve. The partial pressure of oxygen ( pO 2) was measured in the sciatic nerve and the cerebral cortex of adult cats before and during direct, local electrical stimulation of these neural tissues, using stimulus parameters capable of inducing neural injury. pO 2 was monitored by the polarographic method, employing a platinum microelectrode inserted into the tissue adjacent to or beneath the stimulating electrode. In the sciatic nerve there was no marked change in intrafascicular pO 2 in three cats upon initiation of the electrical stimulation. In a fourth animal intraneural pO 2 increased briefly upon intitiation of the stimulation. In no case did the intrafascicular compartment of nerves become significantly hypoxic. In the cerebral cortex, the start of stimulation was accompanied by a significant increase (approximately 12–15 Torr) in intracortical pO 2 beneath the stimulating electrode, and pO 2 remained at or above the pre-stimulus value for the duration of the stimulation. These results show that extracellular hypoxia is unlikely to be a significant factor in the neural injury induced in brain or peripheral nerve by prolonged electrical stimulation.