Biomedical subjects

C B Jenq

Publications and source records attributed to C B Jenq.

18 recordsLinked to original sources

PubMed1991

Mitogenic response of rat Schwann cells to fibroblast growth factors is potentiated by increased intracellular cyclic AMP levels.

Rat sciatic nerve Schwann cells either do not proliferate, or proliferate very slowly, in medium containing 10% fetal bovine serum (FBS). They were previously shown to respond only to a limited number of mitogens associated with cells of central and peripheral nervous systems, which appeared to be distinct from FGFs and PDGF, and to agents that raise intracellular cAMP levels. In a basal medium consisting of 75% DMEM, 25% Ham's F-12, 5 nM sodium selenite, 50 microM 2-amino ethanol, and 2 mM histidine, supplemented with 5% FBS, we showed that aFGF, bFGF, and PDGF were all capable of stimulating Schwann cell growth and the stimulation was greatly potentiated by forskolin and dibutyryl-cAMP. In addition, pretreating culture surface with purified matrix proteins such as laminin, fibronectin, or type 1 collagen, was necessary for obtaining a better cellular response to the mitogenesis of these growth factors even in 10% FBS. Our results clearly indicated that providing a suitable medium and substratum, aFGF, bFGF and PDGF are mitogens for rat sciatic nerve Schwann cells in medium with and without forskolin or dibutyryl-cAMP.

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PubMed1988

Conditioning lesions of peripheral nerves change regenerated axon numbers.

The present study investigates the effects of conditioning lesions on regenerated axon numbers in tributary nerves after a test lesion. If a rat sciatic nerve is crushed 7 and 14 days prior to a test crush, the numbers of regenerated myelinated axons 8 weeks later in the sural nerve (SN) and nerve to the medial gastrocnemius (NMG) are increased, both over normal and over numbers after a single crush. If the lesions are only separated by 2 days, however, the numbers are similar to the numbers after a single crush. Thus conditioning occurs, but a minimum time between crushes is necessary for the effects of conditioning to be manifest. If the intervals between lesions are 14 days, the numbers are similar to those after the 7-day intervals. Moving each successive crush proximally or distally does not change regenerated myelinated axon numbers. Thus increasing the time between lesions after conditioning occurs, at least within the constraints of our paradigm, does not change regenerated axon numbers and the location of the lesion has relatively little bearing on the numbers of axons that regenerate. These findings allow us to change axonal numbers in these tributary nerves in a predictable way, and they are also compatible with the hypothesis that conditioning results from priming of the cell body rather than changes in the environment of the regenerating axons.

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PubMed1987

Single vs multiple somatic nerve crushes in the rat.

Nerve lesions modify regenerative responses to subsequent lesions. Some of the modifications might be useful. To increase our understanding of these modifications, the present study determines myelinated and unmyelinated axon numbers in the distal part of rat sciatic nerve and in 2 smaller branches, the nerve to the medial gastrocnemius muscle and the sural nerve, 8 weeks and 9 months following either single or the last of 3 crushes to the rat sciatic nerve. For myelinated axons, there is a significant and proportional increase distal to the crush in the sciatic nerve and in its smaller tributaries following both single and triple crushes. These increased axons persist. We interpret these data to indicate that some of the regenerating myelinated axons branch at the site of lesion, pass without branching into the tributary nerves, and then presumably find attachments at the periphery. If true, single or multiple crushes might be useful in conditions where it would be desirable to increase numbers of processes from surviving neurons. The major differences between single and triple crushes are that myelinated axons are increased more after triple crush and increase significantly between 8 weeks and 9 months after triple crush but not after single crush. Thus not only myelinated axon numbers, but the timing of the myelination process seems to change if regeneration following single crush is compared to similar regeneration following multiple crushes. Unmyelinated axons do not regenerate in the same way as the myelinated axons.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1987

Permeable tubes increase the length of the gap that regenerating axons can span.

After placement of stumps of transected rat sciatic nerve in an impermeable tube, the maximum gap the axons can span is 10 mm. The present study shows that the regenerating axons cross much longer gaps if the tube is made permeable. This improvement does not require another nerve as a transplant nor the preplacement of extracellular materials in the tube. Possible mechanisms for this improvement are discussed.

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PubMed1987

Sciatic nerve regeneration after autologous sural nerve transplantation in the rat.

The present study is concerned with the question as to whether the size of a nerve used as a transplant to bridge a gap between the stumps of transected nerves has a bearing on the number of axons and the cytological structure of the regenerate. The paradigm is rat sciatic nerve transection with 8 mm of nerve removed with the stumps placed in a silicone tube and two strands of the smaller sural nerve used as bridging transplants. The comparisons are with previously published results where the transplant, which is the removed piece of sciatic nerve, is exactly matched in size and with no transplant in the same regeneration paradigm. One surprising finding is that the size of the transplant does not seem to determine the size of the regenerated nerve. The cytological structure of the regenerated nerve is related to the size of the transplant, however, in that the proportion of axons that regenerate inside and outside the transplanted perineurial tubes differs in relation to the size of the transplant. In addition, although there is an increase in the number of blood vessels in all of these paradigms, the greatest increase is with the sural nerve transplants. The key finding in the study, however, is the similarity in numbers of regenerated axons in the gap, distal stump and tributary nerves when regeneration after sciatic nerve transplantation is compared with regeneration after sural nerve transplantation. Thus, notwithstanding the cytologic differences of the two types of regenerate, regenerated axon numbers are approximately the same. The conclusion is that the size of the transplant determines neither the size of the regenerate nor the numbers of regenerated axons in this paradigm. On the assumption that regeneration is better when axonal numbers are closer to normal, the non-matched sural nerve transplant is approximately equal to the matched sciatic nerve transplant and both are superior to the regeneration that takes place in the absence of a transplant in this paradigm.

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PubMed1987

Nerve regeneration changes with filters of different pore size.

An experimental reason for placing stumps of a transected nerve in an impermeable tube is that factors and soluble substances from the nerve stumps are pooled and separated from cells and soluble substances in the body in general. Previous work showed that certain parameters of regeneration were improved, however, when the impermeable tube was made completely permeable by cutting macroscopic holes in its side. To begin exploring the reasons for these improvements, we covered the holes in the permeable tubes with filters of two different pore sizes, and found that the improvements resulted when the pore size was large enough to allow both fluid and cells to exchange but not when the pore size allowed only fluid to exchange. These findings suggest that cells from the general connective tissue should be given consideration when designing experimental procedures to maximize the regeneration potential of regenerating axons.

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PubMed1987

Numerical patterns of axon regeneration that follow sciatic nerve crush in the neonatal rat.

Different proportions of axons regenerate in cutaneous nerves compared with muscle nerves after sciatic nerve crush in the rat. The questions here are whether or not these differences reflect the proportions of axons that regenerate in the different nerves from which these nerves arise and do the differences persist. The findings indicate that the numbers of axons that regenerate in the muscle nerves do not reflect the numbers in the nerve from which the muscle nerves originate and that these differences persist. This leads to the conclusion that some factors determining numbers of axons in the muscle nerves must operate distal to the lesion. Thus when one is considering mechanisms that control regenerated axon numbers after neonatal nerve crush, one must consider not only the lesion site but also branching and axon diversion far distally, presumably at the origin of the muscle nerves.

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PubMed1986

Postnatal loss of axons in normal rat sciatic nerve.

Myelinated and unmyelinated axons were counted in sciatic nerves of newborn, 5-day-old, 14-day-old, and adult rats. Myelinated axons increase from essentially none at birth to approximately 8,000 in adulthood, but total axon numbers decrease steadily from 33,954 at birth to 22,872 in adulthood. Thus there is a significant postnatal loss of axons from rat sciatic nerve. This loss is, in our opinion, not associated with the death of the cells that give rise to these axons. This is thus an example of a regressive event that probably is of importance in normal neural development, namely the postnatal elimination of axons unaccompanied by death of the neurons that give rise to axons. These findings presumably imply a considerable amount of proximal peripheral axon branching, and the postnatal elimination of axons in the sciatic nerve presumably results from a reduction of this branching. Thus postnatal elimination of processes on, for example, somatic muscle cells may be at least partially the result of long axon elimination rather than local withdrawal of presynaptic processes, as is usually thought to be the case. In addition, an increased number of axons resulting from early postnatal manipulations may indicate cessation of axon loss rather than formation of new axons.

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PubMed1986

The effects of an autologous transplant on patterns of regeneration in rat sciatic nerve.

Autologous transplants are often used in repair of peripheral nerve injury. Quantitative evaluation of the results of such a transplant is obviously desirable. In previous study, we determined numerical and cytologic parameters of the regeneration that followed transection of rat sciatic nerve, but no transplant was used. This work now serves as a basis for evaluating the use of an autologous transplant in the same transection paradigm. Our procedure is to remove 8 mm of sciatic nerve in the thigh. The removed segment is then put into the center of a silicone tube and the proximal and distal stumps of the severed nerve are placed into the ends of the tube. The data show: (1) a high percentage of successful regenerations; (2) a relatively large nerve in the gap; (3) a typical outer perineurium underlying the epineurium; (4) a well-developed fascicular perineurium; and (5) approximately equal numbers of myelinated and unmyelinated axons in the gap and distal stump. If a transplant is not used there are: (1) a greater number of failures of regeneration; (2) a smaller nerve in the gap; (3) a less well-developed fascicular perineurium; (4) unequal numbers of axons in the gap as compared to the distal stump; and (5) no outer perineurium forms. The presence of a typical outer perineurium after a transplant and its absence if a transplant is not used is probably the most striking cytologic difference between the two paradigms. The equal numbers of axons in the gap and distal stump following regeneration after transplantation presumably indicate that all axons in the gap enter the distal stump without branching or ending blindly, a situation that is presumably beneficial and contrasts with the findings when a transplant is not used. Both paradigms show a remarkable increase in the density of blood vessels in the regenerated nerve in the gap between the two stumps. These findings will serve as a basis for further studies on the mechanisms of peripheral nerve regeneration.

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PubMed1986

Regeneration of transected rat sciatic nerves after using isolated nerve fragments as distal inserts in silicone tubes.

We determined blood vessel and perineurial fascicle densities as well as axonal numbers in regenerated rat sciatic nerves 8 weeks after the nerves had been transected, the proximal stumps placed into the proximal ends of silicone tubes, and isolated fragments of nerve placed into the distal ends of the same tubes. The data are compared with data from the normal nerve and from regeneration in a similar paradigm in which the distal stumps were used as the inserts into the distal end of the silicone tubes. A major difference between the two regeneration paradigms was that axons were discouraged from reaching the periphery when the distal insert was an isolated fragment and encouraged to reach the periphery when the distal insert was the distal stump. We found that fascicle and blood vessel densities were greater than normal but less than with the distal stump as the distal insert. Thus we concluded that the nature of the distal insert had a bearing on how many vessels and perineurial fascicles were formed during regeneration in these conditions. Myelinated axon numbers did not differ in the two conditions whereas there were more unmyelinated axons with the isolated distal stump as the distal insert. Thus at this regeneration time the numbers of myelinated axons were not as dependent on the nature of the distal insert as were the numbers of unmyelinated axons. Finally the length of the gap had a great influence on the numbers of axons that regenerated.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1985

Nerve regeneration through holey silicone tubes.

Recent studies focus on regeneration where nerve stumps are placed in a silicone tube. Since the tube is impermeable, the fluid and cells that collect from the stumps bath the axons. This is presumably beneficial. Making the tube permeable by making holes in its walls should change the patterns of regeneration. If this is done, the major cytologic change is an increase in the fascicular perineurium. There are more individual fascicles, more cells line each fascicle and the lining cells are coated by more prominent external laminae than after similar regeneration in a regular silicone tube or in the normal untransected nerve. For axonal numbers, there are more myelinated and unmyelinated axons in the gap and more unmyelinated axons in the distal stump than after regeneration in a regular silicone tube. The numbers in the holey tube regenerate are statistically different from normal but they are closer to normal than after similar regeneration in a regular silicone tube. There are significantly fewer myelinated and unmyelinated axons than in the normal sural nerve after regeneration through a holey tube, but there are more than after regeneration through a regular tube. The numbers of axons in the nerve to the medial gastrocnemius muscle are not significantly different from normal or from the other regeneration paradigms. These data allow the suggestion that regeneration through a silicone tube with macroscopic holes in its walls may be superior in certain respects to regeneration through a regular impermeable silicone tube.

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PubMed1985

Numbers of regenerated axons in tributary nerves following neonatal sciatic nerve crush in rat.

We determined numbers of regenerated axons in 5 tributary nerves 8 weeks after the complete axonal loss that follows crush of newborn rat sciatic nerve. The major findings are: (1) that proportionately many more axons are lost in cutaneous than in muscle nerves, (2) that myelinated axons are greatly increased over normal in two of the muscle nerves, and (3) that unmyelinated axons are normal or close to normal in muscle nerves. The major conclusions are: (1) there is a different pattern of regeneration in cutaneous as compared to muscle nerves after neonatal sciatic nerve crush, and (2) the responses after neonatal crushes are different than after adult nerve crushes.

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PubMed1985

Long-term patterns of axon regeneration in the sciatic nerve and its tributaries.

The present study determines the numbers of axons that regenerate after sciatic nerve transection in the rat. The transections are done by removing either 4 mm or 8 mm of the nerve. The axons are counted in the gap and distal stump of the sciatic nerve and in 5 of its tributaries. Survival time is 9 months which we define as long-term to allow comparison with short-term data obtained after a much shorter survival. The first findings is that the numbers of axons in the gap and distal stump are different in the 2 transection paradigms. For the 4 mm paradigm, more axons than normal appear in the gap and only a fraction of these pass into the distal stump. For the 8 mm paradigm, the numbers of axons in the gap are normal and the numbers in the distal stump do not deviate far from these. Thus by changing only the length of the segment of removed nerve, one causes major differences in the numbers of axons that regenerate. Second the numbers of axons that regenerate in tributary nerves that innervate muscle have a different pattern than the numbers that regenerate into cutaneous nerves. Thus the factors control axonal numbers must be different in the 2 types of nerves. Finally, axons that regenerate into tributary nerves do not, by and large, regenerate in concert with those in the distal stump of the parent nerve. Thus the factors that control axonal numbers in the tributary nerves must be different from those that control the numbers in the distal stump of the parent nerve.

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PubMed1985

Numbers of regenerating axons in parent and tributary peripheral nerves in the rat.

This study is concerned with numerical parameters of axonal regeneration in peripheral nerves. Our first finding is that the number of axons that regenerate into the distal stump of a somatic nerve at a particular time after transection is partially dependent on the type of lesion used to interrupt the axons. The second question concerns the proportion of axons that regenerate into the distal stump of a parent nerve compared to the proportions that regenerate into tributary nerves that arise from the parent. The proportions of regenerated myelinated axons in the nerve to the medial gastrocnemius muscle and myelinated and unmyelinated axons in the sural nerve are the same as the proportions of myelinated and unmyelinated axons that regenerate into the distal stump of the sciatic nerve for the crush, 0 and 4 mm gap transections. Proportionally fewer axons regenerate into the tributary nerves following the 8 mm gap transection, however. This implies that the length of the gap has an influence on whether or not axons in tributary nerves regenerate in concert with axons in the distal stump of the parent nerve. The unmyelinated fibers in the nerve to the medial gastrocnemius muscle are different because they do not regenerate in proportion to those in the distal stump of the sciatic nerve. We also provide evidence to indicate that myelinated axons branch whereas unmyelinated fibers end blindly when they enter the distal stump after crossing a sciatic nerve transection. Finally the normal arrangement of perineurial cells seems to be disrupted after the sciatic nerve regenerates across a gap.

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PubMed1984

Regeneration of axons in tributary nerves.

The present study tests 2 hypotheses: (1) that the numbers of axons that regenerate into a tributary nerve are in part dependent on the type of lesion used to transect the axons in the parent nerve; and (2) that the numbers of axons that regenerate will be different in different tributary nerves. Axons were counted in the sural nerve and the nerve to the medial gastrocnemius muscle 8 weeks following crush, simple transection, transection with removal of 4 mm and transection with removal of 8 mm of the sciatic nerve in the rat. The counts of myelinated and unmyelinated axons are presented in the text. If axon numbers in the 2 nerves are normalized, the proportion of regenerated to normal myelinated axon numbers are approximately the same in the 2 nerves, with more regenerated axons than normal following crush, simple transection, or 4 mm gap transection and fewer following 8 mm gap transection. The unmyelinated axons behave differently. In the nerve to the medial gastrocnemius muscle, the numbers of unmyelinated axons are greater than or equal to the normal numbers following our various surgical paradigms whereas in the sural nerve there are always fewer unmyelinated axons than normal. These findings indicate that the above hypotheses are correct for the nerves tested in the rat.

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PubMed1984

The effects of nerve growth factor and its antibodies on axonal numbers in the medial gastrocnemius nerve of the rat.

The effects of the administration of nerve growth factor (NGF) or its antibody (anti-NGF) on axonal populations in a peripheral nerve have been investigated. The nerve is a motor nerve, the nerve to the medial gastrocnemius muscle in the rat. The findings are that the administration of NGF at birth and for 28 days thereafter results in an increase of 42% of the unmyelinated axons in this nerve as compared to normal, and that the administration of anti-NGF in the same way results in a 20 and 30% decrease, respectively, in the myelinated and unmyelinated axons in this nerve. We speculate that the unmyelinated axon increase after NGF administration indicates an increase in post-ganglionic sympathetic axons and that the decreases in myelinated and unmyelinated axons after anti-NGF administration indicate decreases in both post-ganglionic sympathetic and sensory axons. The implications of these findings are discussed.

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PubMed1984

Effects of sciatic nerve regeneration on axonal populations in tributary nerves.

The present study is a determination of the numbers of axons in the sural nerve and nerve to the medial gastrocnemius muscle following section and regeneration of the sciatic nerve in the rat. The data indicate that there is a significant increase in both myelinated and unmyelinated axons in the nerve to the medial gastrocnemius muscle and a significant increase in myelinated but a significant decrease in unmyelinated axons in the sural nerve. Thus axonal numbers do not return to normal and the axonal responses are different in different tributary nerves when the parent nerve is cut and then regenerates.

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PubMed1981

Direct retinal input to the limbic system of the rat.

Retinal projections in rats were studied using anterograde horseradish peroxidase (HRP) tracing and electron microscopic (EM) degeneration. HRP-labeled axons were observed to leave the optic tract in the vicinity of the lateral geniculate nucleus and enter the stria terminalis where they coursed anteriorly to the bed nucleus of the stria terminalis (BNST), and the anterodorsal (TAD) and anteroventral (TAV) thalamic nuclei. After enucleation, selected areas studied with EM confirmed that retinal presynaptic terminals are located in the BNST and TAV. These results support the finding of Conrad and Stumpf that the retina has a direct link to the limbic system.

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