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Biomedical subjects

T M Brushart

Publications and source records attributed to T M Brushart.

At least 19 recordsLinked to original sources
PubMed1999

The effects of free fat grafts on the stiffness of the rat sciatic nerve and perineural scar.

We developed a new quantitative rat sciatic nerve model to test whether free fat grafts can reduce postoperative perineural scar formation. Epineurectomies of sciatic nerves were performed to create scar. The force required to distract the nerve a unit distance was measured after surgery to determine the time of maximal scar formation. Nerve stiffness normalized for rat weight was statistically greater at 2 months after the initial dissection (0.097+/-0.009 g/mm/g rat weight; n = 10 limbs) than rat limbs that had not undergone a previous dissection (0.075+/-0.012 g/mm/g rat weight). Perineural scar thickness was thicker at 2 months than the perineural tissue in preoperative controls. Free fat grafts decreased nerve stiffness at 2 months (0.078+/-0.012 g/mm/g rat weight) in comparison to the contralateral surgical control limb without a fat graft (0.094+/-0.014 g/mm/g rat weight). Free fat grafts reduced the strength of postoperative perineural scar in this surgical model; however, they were associated with an unexpected finding of substantial postoperative neuropathy.

Adipose Tissue↗
PubMed1998

Contributions of pathway and neuron to preferential motor reinnervation.

Motor axons regenerating after transection of mixed nerve preferentially reinnervate distal muscle branches, a process termed preferential motor reinnervation (PMR). Motor axon collaterals appear to enter both cutaneous and muscle Schwann cell tubes on a random basis. Double-labeling studies suggest that PMR is generated by pruning collaterals from cutaneous pathways while maintaining those in motor pathways (the "pruning hypothesis"). If all collaterals projecting to muscle are saved, then stimulation of regenerative sprouting should increase specificity by increasing the number of motoneurons with at least one collateral in a muscle pathway. In the current experiments, collateral sprouting is stimulated by crushing the nerve proximal to the repair site before suture, a maneuver that also conditions the neuron and predegenerates the distal pathway. Control experiments are performed to separate these effects from those of collateral generation. Experiments were performed on the rat femoral nerve and evaluated by exposing its terminal cutaneous and muscle branches to HRP or Fluoro-Gold. Crush proximal to the repair site increased motor axon collaterals at least fivefold and significantly increased the percentage of correctly projecting motoneurons, consistent with the pruning hypothesis. Conditioning the nerve with distal crushes before repair had no effect on specificity. A graft model was used to separate the effects of collateral generation and distal stump predegeneration. Previous crush of the proximal femoral nerve significantly increased the specificity of fresh graft reinnervation. Stimulation of regenerative collateral sprouting thus increased PMR, confirming the pruning hypothesis. However, this effect was overshadowed by the dramatic specificity with which predegenerated grafts were reinnervated by fresh uncrushed proximal axons. These unexpected effects of predegeneration on specificity could involve a variety of possible mechanisms and warrant further study because of their mechanistic and clinical implications.

Animals↗
PubMed1998

The effect of denervated muscle and Schwann cells on axon collateral sprouting.

The effects of denervated muscle and Schwann cells on collateral sprouting from peripheral nerve were studied in the peroneal and tibial nerves of 48 Sprague-Dawley rats. Three groups were prepared. In group MSW (muscle-Schwann cell-window), the peroneal nerves were transected 3 mm below the sciatic bifurcation. The proximal stumps were sealed in a blocked tube to prevent regeneration and the distal stumps were implanted into denervated muscle cells that were wrapped around the ipsilateral tibial nerve, which had a window of perineurium resected. Schwann cells from the ipsilateral sural nerve were implanted into the muscle. Group MS (muscle-Schwann cell) was similar to group MSW, except that the tibial nerve perineurium was kept intact. In group MW (muscle-window), the muscle was prepared without Schwann cells and the tibial nerve perineurium was windowed. S-100 immunostain was used to identify the Schwann cells surviving 1 week after transplantation. After 16 weeks of regeneration, horseradish peroxidase tracer was used to label motor neurons and sensory neurons reinnervating the peroneal nerve. Myelinated axons of the reinnervated peroneal nerves were quantified with the Bioquant OS/2 computer system (R&M Biometrics, Nashville, TN). A mean of 169 motor neurons in group MSW, 64 in group MW, and 26 in group MS reinnervated the peroneal nerve. In the dorsal root ganglion, the mean number of labeled sensory neurons was 1,283 in group MSW, 947 in group MS, and 615 in group MW. The mean number of myelinated axons in the reinnervated peroneal nerve was 1,659 in group MSW, 359 in group MS, and 348 in group MW. Reinnervated anterolateral compartment muscles in group MSW were significantly heavier than those in group MS or MW. This study demonstrates that the transplantation of denervated muscle and Schwann cells promotes motor and sensory nerve collateral sprouting through a perineurial window.

Animals↗
PubMed1997

Neurotization of the rat soleus muscle: a quantitative analysis of reinnervation.

Neurotization--reinnervation of muscle by direct nerve implantation--has been the subject of several reports. The underlying neurobiology, however, has not been adequately studied. The use of a combined silver-acetylcholinesterase stain was used in this study to identify reinnervated motor endplates and to quantify motor endplates reinnervated by the neurotization process. This study examined the effect of distance between nerve implantation and native motor endplate zone on the formation of ectopic motor endplates and on the total number of motor endplates reinnervated. Experiments were performed on the rat soleus muscle. The transected tibial nerve was implanted directly into the motor endplate zone (near, n = 10) or distally, far from the motor endplate zone (far, n = 10). After a reinnervation interval, frozen sections were processed to demonstrate both axons and motor endplates. In the near group, a mean of 566 motor endplates were reinnervated in the native motor endplate zone and a mean of only 13 in distant locations. In the far group, a mean of 362 motor endplates were reinnervated in the native zone, while a mean of 477 were reinnervated in distant locations. Significantly more ectopic motor endplates were generated by far implantation, and native motor endplates were increased by near implantation. The total number of motor endplates was independent of implant location. These experiments demonstrate that the distance between implanted nerve and the native motor endplate zone influences the morphology of reinnervation.

Acetylcholinesterase↗
PubMed1996

Reinnervation accuracy of the rat femoral nerve by motor and sensory neurons.

Previous studies in the rat femoral nerve have shown that regenerating motor neurons preferentially reinnervate a terminal nerve branch to muscle as opposed to skin, a process that has been called preferential motor reinnervation. However, the ability of sensory afferent neurons to accurately reinnervate terminal nerve pathways has been controversial. Within the dorsal root ganglia, sensory neurons projecting to muscle are interspersed with sensory neurons projecting to skin. Thus, anatomical studies assessing the accuracy of sensory neuron regeneration have been hampered by the inability to reliably determine their original innervation status. A sensory neuron that regenerated an axon into a terminal nerve branch to muscle might represent either an appropriate return of an original sensory afferent to muscle stretch receptors or the inappropriate recruitment of a cutaneous sensory afferent that originally innervated skin. The current experiments used a labeling strategy that effectively labels motor and sensory neurons projecting to a terminal nerve branch before experimental manipulation of the parent mixed nerve. Our results confirm previous observations concerning preferential motor reinnervation for motor neurons, and show for the first time anatomical evidence of specificity during regeneration of sensory afferent projections to muscle. In addition, the accuracy of sensory afferent regeneration was highly correlated with the accuracy of motor regeneration. This suggests that these two distinct neuronal populations that project to muscle respond in parallel to specific guidance factors during the regeneration process.

Animals↗
PubMed1995

Joseph H. Boyes Award. Dispersion of regenerating axons across enclosed neural gaps.

Tubular prostheses support peripheral axon regeneration across gaps of up to 3 cm in the primate. However, the precision with which axons cross a gap and reinnervate the periphery remains controversial. These experiments use continuous tracing of regenerated rat sciatic nerve axons with HRP-WGA to examine the dispersion of axons as they cross a gap, and the effects on this dispersion of gap distance and fascicular orientation. Proximal and distal tibial and peroneal fascicles were precisely oriented about the longitudinal midplane of a silicon tube, with correct or reversed fascicular alignment and gaps of 2 mm and 5 mm. After 6 weeks of regeneration, HRP-WGA was applied to the distal peroneal fascicle to continuously label its reinnervating axons. These axons tended to grow straight across the tube, with dispersion increasing as a factor of distance when correct fascicular alignment was maintained. However, when fascicular alignment was reversed, axonal dispersion was determined by fascicular size rather than fascicular identity. These experiments provide no evidence for neurotropic interactions promoting "correct" fascicular reinnervation. Progressive axonal dispersion and the absence of factors to promote fascicular specificity should result in an increase of random reinnervation and functional disruption with larger gaps. An enclosed gap is not an acceptable substitute for nerve graft when reconstructing a nerve that serves multiple functions.

Animals↗
PubMed1994

The L2/HNK-1 carbohydrate is preferentially expressed by previously motor axon-associated Schwann cells in reinnervated peripheral nerves.

The carbohydrate epitope L2/HNK-1 (hereafter designated L2) is expressed in the adult mouse by myelinating Schwann cells of ventral roots and muscle nerves, but rarely by those of dorsal roots or cutaneous nerves. Since substrate-coated L2 glycolipids promote outgrowth of cultured motor but not sensory neurons, L2 may thus influence the preferential reinnervation of muscle nerves by regenerating motor axons in vivo. In the present study, we have analyzed the influence of regenerating axons on L2 expression by reinnervated Schwann cells by directing motor or sensory axons into the muscle and cutaneous branches of femoral nerves of 8-week-old mice. We observed that regenerating axons from cutaneous branches did not lead to immunocytochemically detectable L2 expression in muscle or cutaneous nerve branches. Axons regenerating from muscle branches led to a weak L2 expression by few Schwann cells of the cutaneous branch, but provoked a strong L2 expression by many Schwann cells of the muscle branch. Myelinating Schwann cells previously associated with motor axons thus differed from previously sensory axon-associated myelinating Schwann cells in their ability to express L2 when contacted by motor axons. This upregulation of L2 expression during critical stages of reinnervation may provide motor axons regenerating into the appropriate, muscle pathways with an advantage over those regenerating into the inappropriate, sensory pathways.

Animals↗
PubMed1993

Prolonged survival of transected nerve fibres in C57BL/Ola mice is an intrinsic characteristic of the axon.

Transected axons in C57BL/Ola mice survive for extraordinary lengths of time as compared to those of normal rodents. The biological difference in the substrain that confers the phenotype of prolonged axonal survival is unknown. Previous studies suggest that 'defect' to be a property of the nervous system itself, rather than one of haematogenous cells. Neuronal or non-neuronal elements could be responsible for this phenotype. This study was undertaken to determine whether Schwann cells, the most numerous of the non-neuronal cells intrinsic to the peripheral nerve, are responsible for delayed degeneration of transected axons. We created sciatic nerve chimeras by transplanting nerve segments between standard C57BL/6 and C57BL/Ola mice, allowing regeneration of host axons through the grafts containing donor Schwann cells. These nerves were then transected and the time course of axonal degeneration was observed. The results show that fast or slow degeneration is a property conferred by the host, and therefore cannot be ascribed to the Schwann cells. Similarly, transected C57BL/Ola axons in explanted dorsal root ganglia cultures survived longer than transected axons from standard mice. Taken together these results indicate that the responsible abnormality is intrinsic to the C57BL/Ola axon.

Animals↗
PubMed1993

Motor axons preferentially reinnervate motor pathways.

Motor axons regenerating after transection of mixed nerve preferentially reinnervate distal motor branches and/or muscle, a process termed "preferential motor reinnervation." Collaterals of a single motor axon often enter both sensory and motor Schwann cell tubes of the distal stump; specificity is generated by pruning collaterals from sensory pathways while maintaining those in motor pathways. Previous experiments in the rat femoral nerve model evaluated reinnervation of the femoral motor branch and quadriceps muscle as a unit. In this study, pathway contributions are analyzed separately by denying muscle contact, or by reinnervating muscle through inappropriate, formerly sensory pathways. Motor axons preferentially reinnervate motor pathways, even when these pathways end blindly in a silicon tube. If the femoral nerve is removed as a graft and reinserted with correct or reversed alignment of the sensory and motor branches, more motoneurons reinnervate muscle through correct motor than through incorrect sensory pathways. Motor pathways thus differ from sensory pathways in ways that survive Wallerian degeneration and transplantation as a graft, and that can be used by regenerating motor axons as a basis for collateral pruning and specificity generation.

Animals↗
PubMed1991

Central course of digital axons within the median nerve of Macaca mulatta.

The traditional view that axons are not functionally grouped within proximal human nerve is based on the interfascicular dissections of Sunderland ('45). However, microstimulation and microneurography (Schady et al., '83a; Hallin, '90) reveal proximal grouping of cutaneous sensory axons from small areas of skin. In the present studies, conjugates of horseradish peroxidase with wheat germ agglutinin (HRP-WGA) were used to trace the course of digital nerve axons within the median nerve of Macaca mulatta. The electrophysiologic findings were confirmed, suggesting the potential for precise surgical realignment of functionally related axons even after proximal nerve transection. Radial digital nerves were labeled in the thumb (bilateral, 1 animal), the index finger (unilateral, 2 animals), and the middle finger (bilateral, 1 animal). Median nerve cross sections were cut at 1-cm intervals, treated with tetramethyl benzidine to demonstrate HRP-WGA within axons, and compiled to form maps of each digital nerve "territory" within the median nerve. These territories were limited to a single, densely labeled fascicle at the wrist level. They expanded somewhat in the forearm to encompass clusters of labeled axons within a matrix of unlabeled axon profiles. The clusters were more loosely packed in the arm, occupying 1/3 to 1/6 of the nerve cross section at the entrance to the brachial plexus. The three digital nerve territories studied were widely separated at the wrist level. In the proximal arm, there was moderate intermingling of axons from adjacent digits, but those to the middle finger and thumb remained segregated. Territory configuration differed widely overall, but was moderately constant for each digit. The location of territories within the nerve was often strikingly similar from right to left and from animal to animal, with occasional prominent variations reflecting isolated rotation of one nerve.

Animals↗
PubMed1989

Somatotopy of digital nerve projections to the dorsal horn in the monkey.

The dorsal horn projection patterns of finger nerves were investigated in four Macaca mulatta monkeys. Proper digital branches of the median nerves, serving the radial aspect of a digit on each hand, were loaded with wheatgerm agglutinin-horseradish peroxidase complex (WGA:HRP). The distribution of the lectin-enzyme complex was mapped in the right and left dorsal horns. The dorsal horn projections of the digital nerves were localized in segments C6-C8 in laminae I-VI, primarily in laminae I-IV. The wedge-shaped termination zones were somatotopically organized, in agreement with the projections of the digits in cats. The fingers are represented medially, as they are in the cat. This similarity suggests that there is a mediolateral gradient of dorsal horn organization similar to that of the cat, with distal skin represented medially and proximal skin represented laterally. The rostrocaudal trajectory of finger representation, with digit 1 most rostral and digit 5 most caudal, is also in agreement with the organization of hindlimb toe projections in the cat. There was a high degree of bilateral symmetry for homologous nerves, and little overlap of projections from nerves innervating adjacent fingers. The sample size was too small to permit us to assess interanimal variation. These results suggest a similar somatotopy of projections, and presumably of dorsal horn cell somatotopy, in monkey and cat.

Afferent Pathways↗
PubMed1989

Somatotopy of digital nerve projections to the cuneate nucleus in the monkey.

Somatotopic arrangements of cells and fibers within the dorsal columns and the dorsal column nuclei have been mapped most precisely by electrophysiological recording methods. This study uses an anatomical approach to evaluate the precision of individual digital nerve projections to the cuneate nucleus (CN) in young macaque monkeys. Digital nerves supplying about one-half the palmar skin of a digit were surgically exposed, cut, and treated with wheatgerm agglutinin conjugated to horseradish peroxidase (WGA:HRP) on 3 successive days. After 2 additional days, animals were killed and medullas were recovered for study of serial sections reacted to display axons labeled by transganglionic transport of label. Labeled afferent fibers from each digit were found within a circumscribed columnar zone extending through the caudal CN and rostrally throughout the pars rotunda of CN. At caudal levels, diffuse projections reach the dorsal edge of the CN; more rostrally, they shift into deeper parts of the nucleus and are heaviest along its ventral and medial edges at levels near the obex. Fibers from the thumb (digit 1) project lateral (and ventral) to those from digit 2, and projections from digit 3 are medial to those from 2. Each digital projection field is closely adjacent to that from the adjacent digit. Few fibers extend to the rostral CN. Projection fields of homologous digits are quite symmetrical on the two sides. Although there do seem to be some differences in the somatotopic arrangement of digital input in macaques compared to other nonprimate mammals studied previously, these observations (precisely organized, circumscribed fields for separate digits) define a system well designed for transmission of data encoding spatial relationships.

Afferent Pathways↗
PubMed1988

Preferential reinnervation of motor nerves by regenerating motor axons.

Regeneration of axons into inappropriate distal nerve branches may adversely affect functional recovery after peripheral nerve suture. The degree to which motor axons reinnervate sensory nerves, and vice versa, has not been determined. In these experiments, HRP is used to quantify the sensory and motor neurons that reinnervate sensory and motor branches of the rat femoral nerve after proximal severance and repair. Motoneurons preferentially reinnervate the motor branch in juveniles and adults, even if the repair is intentionally misaligned or a gap is imposed between proximal and distal stumps. A specific interaction thus occurs between regenerating motor axons and the Schwann cell tubes that lead to the motor branch. This interaction is independent of mechanical axon alignment.

Animals↗
PubMed1987

Selective reinnervation of distal motor stumps by peripheral motor axons.

Random matching of regenerating axons with Schwann tubes in the distal nerve stump is thought to contribute to the often poor results of peripheral nerve repair. Motor axons would be led to sensory end organs and sensory axons to motor end plates; both would remain functionless. However, the ability of regenerating axons to differentiate between sensory and motor environments has not been adequately examined. The experiments reported here evaluated the behavior of regenerating motor axons when given equal access to distal sensory and motor nerve stumps across an unstructured gap. "Y"-shape silicon chambers were implanted within the rat femoral nerve with the proximal motor branch as axon source in the base of the Y. The distal sensory and motor branches served as targets in the branches of the Y, and were placed 2 or 5 mm from the axon source. After 2 months for axon regeneration, horseradish peroxidase was used to label the motoneurons projecting axons into either the motor or the sensory stump. Equal numbers of motoneurons were labeled from the sensory and motor stumps at 2 mm, but significantly more motoneurons were labeled from the motor stump at 5 mm. (P = 0.016). This finding is consistent with selective reinnervation of the motor stump. Augmentation of this phenomenon to produce specific reunion of individual motor axons could dramatically improve the results of nerve suture.

Animals↗
PubMed1985

Nerve regeneration through biodegradable polyester tubes.

One approach to repair of transected nerves is to attempt extrinsic guidance of axons across the gaps. We inserted the proximal and distal stumps of severed mouse sciatic nerves into opposite ends of biodegradable polyester tubes. The nerves and ensheathing tubes were examined after postoperative survival times of as long as 2 years. Myelinated fiber number in each successfully regenerated nerve was measured and correlated with the tube's residual lumen size. In selected regenerated nerves axonal sizes and myelin sheath widths were sampled and compared with control values. Swelling and deformation of tube walls occurred in nearly all tubes. Successful regeneration was obtained through more than half of the implants, and was more probable in tubes with larger initial lumens. Myelinated fiber number in regenerated nerves ranged from 231 to 3561 (normally 3900 to 4200); larger values again were found in tubes with larger initial lumens. Mean axonal areas in regenerated nerves were roughly half of normal, though myelin sheaths became appropriately thick. We concluded that the more biodegradable a tube, the more likely it was to incur distortion and luminal narrowing. Tube composition per se seemed of importance mainly as it related to maintenance of adequate luminal size over the length of the degrading tubes; luminal adequacy, not tube composition, seemed paramount in determining the extent of nerve regeneration.

Animals↗
PubMed1985

Allograft bone for metacarpal reconstruction.

Banked allograft bone has been used for metacarpal reconstruction in 10 patients. In one patient, allograft replaced the shafts of the fourth and fifth metacarpals that were lost as the result of an injury from an explosion. In the remaining nine, allograft was used as an intercalary bone after distraction lengthening of the metacarpal. The first metacarpal was lengthened in seven patients; four had hypoplasia of the thumb and three had partial thumb amputation. One patient with hypoplasia of the ulnar side of the hand had the fourth and fifth metacarpals lengthened, and the fifth metacarpal was lengthened in another. Of the 12 allografts used, radiographic and clinical evidence of bone union occurred at 23 of the 24 allograft/recipient bone interface sites. Most patients had no callus formation. This suggested primary bone healing. Recipient new bone appeared to cross the recipient/donor interface and replace the allograft by "creeping substitution" within 6 months to 1 year. The density and trabecular pattern of the allograft bone gradually assumed that of the recipient's bone. There was no clinical or radiographic evidence of rejection and no evidence of infection, abnormal swelling, or bone resorption. Nine of the 10 patients had improved function as determined by objective and subjective evaluation. Banked allograft bone offers two advantages over autogenous bone for reconstructive hand surgery: There is no donor site morbidity, and large defects can be filled with cylindric cortical bone of appropriate size and shape, which offers excellent stability as an intercalary graft.

Adolescent↗
PubMed1983

Specificity of muscle reinnervation after epineurial and individual fascicular suture of the rat sciatic nerve.

We experimentally analyzed the specificity of muscle reinnervation after suture and regeneration of rat sciatic nerve. We used a horseradish peroxidase (HRP) technique of axon tracing to compare the number and location of motoneurons that innervate muscle via the peroneal nerve after epineurial and individual fascicular suture of the parent sciatic nerve. These motoneurons are significantly reduced in number from control levels and are often in spinal cord locations that indicate previous innervation of antagonistic muscle via the tibial nerve. This inappropriate reinnervation of peroneal muscle by tibial motoneurons is minimized by individual fascicular suture without compromise of overall reinnervation. Our findings thus support the hypothesis that individual fascicular suture may avoid distortion of the central connections of peripheral units.

Animals↗