|10-20-2001, 01:14 PM||#1|
Join Date: Jul 2001
Location: Little Rock,AR
Dr. John Houle?
I was wondering if anyone has any information on Dr. John Houle? I read in Luba's book about him. He is doing research in chronics and he is from the University of Arkansas for Medical Research in Little Rock. I'm also from Little Rock and to see someone from my area working toward a cure is very exciting. Any additional info would be appreciated. I will let you guys know if I find out anything. Thanks, Josh
|10-20-2001, 10:25 PM||#2|
Join Date: Jul 2001
Location: New Brunswick, NJ, USA
Here is a web site that describes some of John's work http://anatomy.uams.edu/HTMLpages/an...tml/Houle.html
Here is a list of abstracts of his work related to spinal cord injury.
1. Houle JD and Jin Y (2001). Chronically injured supraspinal neurons exhibit only modest axonal dieback in response to a cervical hemisection lesion. Exp Neurol. 169 (1): 208-17. Summary: This study examined the extent of axon retraction (dieback) exhibited by injured brain stem neurons in a chronic spinal cord injury (SCI) condition. Adult female rats subjected to a cervical (C3) hemisection lesion were sacrificed 1, 4, 8, or 14 weeks after injury and the spinal cord from C1 to the lesion cavity was removed. One week prior to sacrifice, a microinjection of biotinylated dextran amine (BDA, 0.5 microliter) was made into the red nucleus, lateral vestibular nucleus, or medullary reticular formation of each animal. Horizontal cryostat sections were processed with avidin-HRP to detect supraspinal axons anterogradely labeled with BDA. Terminal end bulbs of axons were identified and their distance from the lesion site was measured by a computerized image analysis program. At all postinjury intervals, numerous rubrospinal, vestibulospinal, and reticulospinal tract axons were found immediately adjacent to the lesion site and over 60% of all terminals were within 500 micrometer at 1 and 4 weeks. The mean axonal distance of 450-500 micrometer from the lesion indicated that many injured axons had retracted farther than 500 micrometer from the lesion site; however, long-term maintenance of the mean axonal distance from the lesion at less than 500 micrometer indicated the absence of progressive dieback after SCI. While some modest changes occur in specific supraspinal pathways following SCI, axonal retraction does not appear to be a contributing factor to the diminished regenerative effort by certain brain stem neurons that has been observed at long postinjury intervals. Copyright 2001 Academic Press. <http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11312573> Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock, Arkansas, 72205, USA.
2. Jin Y, Tessler A, Fischer I and Houle JD (2000). Fibroblasts genetically modified to produce BDNF support regrowth of chronically injured serotonergic axons. Neurorehabil Neural Repair. 14 (4): 311-7. Summary: Cells genetically modified to release a variety of growth and/or neurotrophic factors have been used for transplantation into the injured spinal cord as a means to deliver therapeutic products. Axon growth into and through such transplants has been demonstrated after intervention after an acute injury. The present study examined their potential to support regeneration in a chronic injury condition. Five weeks after a cervical hemisection in adult rats, the lesion site was debrided of scar tissue and expanded in both rostral and caudal directions. Animals received a transplant of cultured normal fibroblasts (control) or fibroblasts genetically modified to produce brain-derived neurotrophic factor (BDNF). Six weeks later, animals were killed to determine the extent of growth of serotonergic axons into the transplant. Axons immunoreactive for serotonin (5-HT-ir) were found to cross the rostral interface of host spinal cord readily with either type of fibroblast cell transplant, but the number and density of 5-HT- ir axons extending into the BDNF-producing transplants was markedly greater than those in the control fibroblasts. Axons coursed in all directions among normal fibroblast transplants, whereas growth was more oriented along a longitudinal plane when BDNF was being released by the transplanted cells. The length of growth and the percentage of the transplant length occupied by 5-HT-ir axons were significantly greater in BDNF-producing transplants than in the normal fibroblasts. Many serotonergic axons approached the caudal end of the BDNF-producing cell transplants, although most failed to penetrate the host spinal cord distal to the lesion. These results indicate that whereas fibroblast cell transplants alone can support regrowth of axons from chronically injured supraspinal neurons, modification of these cells to produce BDNF results in a significant increase in the extent of growth into the transplant. <http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11402881> Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
3. Dupont-Versteegden EE, Murphy RJ, Houle JD, Gurley CM and Peterson CA (2000). Mechanisms leading to restoration of muscle size with exercise and transplantation after spinal cord injury. Am J Physiol Cell Physiol. 279 (6): C1677-84. Summary: We have shown that cycling exercise combined with fetal spinal cord transplantation restored muscle mass reduced as a result of complete transection of the spinal cord. In this study, mechanisms whereby this combined intervention increased the size of atrophied soleus and plantaris muscles were investigated. Rats were divided into five groups (n = 4, per group): control, nontransected; spinal cord transected at T10 for 8 wk (Tx); spinal cord transected for 8 wk and exercised for the last 4 wk (TxEx); spinal cord transected for 8 wk with transplantation of fetal spinal cord tissue into the lesion site 4 wk prior to death (TxTp); and spinal cord transected for 8 wk, exercised for the last 4 wk combined with transplantation 4 wk prior to death (TxExTp). Tx soleus and plantaris muscles were decreased in size compared with control. Exercise and transplantation alone did not restore muscle size in soleus, but exercise alone minimized atrophy in plantaris. However, the combination of exercise and transplantation resulted in a significant increase in muscle size in soleus and plantaris compared with transection alone. Furthermore, myofiber nuclear number of soleus was decreased by 40% in Tx and was not affected in TxEx or TxTp but was restored in TxExTp. A strong correlation (r = 0.85) between myofiber cross-sectional area and myofiber nuclear number was observed in soleus, but not in plantaris muscle, in which myonuclear number did not change with any of the experimental manipulations. 5'-Bromo-2'-deoxyuridine-positive nuclei inside the myofiber membrane were observed in TxExTp soleus muscles, indicating that satellite cells had divided and subsequently fused into myofibers, contributing to the increase in myonuclear number. The increase in satellite cell activity did not appear to be controlled by the insulin-like growth factors (IGF), as IGF-I and IGF-II mRNA abundance was decreased in Tx soleus and plantaris, and was not restored with the interventions. These results indicate that, following a relatively long postinjury interval, exercise and transplantation combined restore muscle size. Satellite cell fusion and restoration of myofiber nuclear number contributed to increased muscle size in the soleus, but not in plantaris, suggesting that cellular mechanisms regulating muscle size differ between muscles with different fiber type composition. <http://www.ncbi.nlm.nih.gov/htbin-po...r&uid=11078681
http://ajpcell.physiology.org/cgi/co...t/279/6/C1677> Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
4. Houle JD, Morris K, Skinner RD, Garcia-Rill E and Peterson CA (1999). Effects of fetal spinal cord tissue transplants and cycling exercise on the soleus muscle in spinalized rats. Muscle Nerve. 22 (7): 846-56. Summary: Studies were carried out to determine if an intraspinal transplant (Trpl) of fetal spinal cord tissue or hind limb exercise (Ex) affected the changes in myosin heavy chain (MyHC) composition or myofiber size that occur following a complete transection (Tx) of the lower thoracic spinal cord of the adult rat. In one group of animals, transplants were made acutely, whereas in a second group, daily cycling exercise was initiated 5 days after injury, with animals in both groups being sacrificed 90 days after injury. The soleus muscle is normally composed of myofibers expressing either type I (90%) or type IIa (10%) MyHC. Following a spinal transection, expression of type I MyHC isoform decreased (18% of myofibers), type IIa MyHC expression increased (65% of myofibers), and the majority of myofibers (80%) expressed type IIx MyHC. Most myofibers coexpressed multiple MyHC isoforms. Compared with Tx only, with Ex or with Trpl, there was a decrease in the number of myofibers expressing type I or IIa isoforms but little change in expression of IIx MyHC. Myofibers expressing the IIb isoform appeared in several transplant recipients but not after exercise. Transection resulted in atrophy of type I myofibers to approximately 50% of normal size, whereas myofibers were significantly larger after exercise (74% of control) and in Trpl recipients (77% of control). Type IIa myofibers also were significantly larger in Trpl recipients compared with the Tx only group. Overall, the mean myofiber size was significantly greater after exercise and in Trpl recipients compared with myofibers in Tx only animals. Thus, although neither strategy shifted the MyHC profile towards the control, both interventions influenced the extent of atrophy observed after spinalization. These data suggest that palliative strategies can be developed to modulate some of the changes in hind limb muscles that occur following a spinal cord injury. <http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10398201> Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
5. Houle JD and Ye JH (1999). Survival of chronically-injured neurons can be prolonged by treatment with neurotrophic factors. Neuroscience. 94 (3): 929-36. Summary: Axonal regeneration by chronically-injured supraspinal neurons can be enhanced by neurotrophic factor treatment at the site of injury, although the number of regenerating neurons decreases as the interval between spinal cord injury and treatment increases. This study investigated whether this decline in regenerative response could be due to continued loss of neurons during the post-injury period. Adult rats received a cervical hemisection lesion and axotomized neurons were labeled by retrograde transport of True Blue from the lesion site. Animals were killed one, four or eight weeks after injury and surviving neurons (True Blue-labeled) were counted in the red nucleus and lateral vestibular nucleus. The neuron number in the lateral vestibular nucleus was stable for eight weeks after spinal cord injury, while survival in the red nucleus decreased by 25% between four and eight weeks. To test how neurons respond to a second injury with or without trophic factor treatment, at four, eight, 14 or 22 weeks after injury the lesion cavity was enlarged by 0.5 mm in a rostral direction. Gel foam saturated with ciliary neurotrophic factor, brain-derived neurotrophic factor or basic fibroblast growth factor was placed into the cavity. Animals were killed four weeks later. Re-injury of the spinal cord caused a significant decrease in neuron survival in both the red nucleus and lateral vestibular nucleus, the effects of which were lessened by treatment with ciliary neurotrophic factor or brain-derived neurotrophic factor for the red nucleus and with ciliary neurotrophic factor for the lateral vestibular nucleus, when re-injured at four or eight weeks. Basic fibroblast growth factor did not affect neuron survival at any time post-injury. Ciliary neurotrophic factor was not effective with longer delays (14 or 22 weeks) between the initial injury and re-injury. These results indicate a delayed pattern of secondary neuronal cell loss after spinal cord injury that is exaggerated by re-injury, but which can be ameliorated by treatment with neurotrophic factors. <http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10579585> Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock 72205, USA. email@example.com
6. Dupont-Versteegden EE, Murphy RJ, Houle JD, Gurley CM and Peterson CA (1999). Activated satellite cells fail to restore myonuclear number in spinal cord transected and exercised rats. Am J Physiol. 277 (3 Pt 1): C589-97. Summary: In this study, possible mechanisms underlying soleus muscle atrophy after spinal cord transection and attenuation of atrophy with cycling exercise were studied. Adult female Sprague-Dawley rats were divided into three groups; in two groups the spinal cord was transected by a lesion at T10. One group was transected and killed 10 days later, and another group was transected and exercised for 5 days starting 5 days after transection. The third group served as an uninjured control. All animals received a continuous-release 5'-bromo-2'-deoxyuridine pellet 10 days before they were killed. Transection alone and transection with exercise lead to activation of satellite cells, but only the exercise group showed a trend toward an increase in the number of proliferating satellite cells. In all cases the number of activated satellite cells was significantly higher than the number that divided. Although the number of cells undergoing proliferation increased with exercise, no increase in fusion of satellite cells into muscle fibers was apparent. Spinal cord transection resulted in a 25% decrease in myonuclear number, and exercise was not associated with a restoration of myonuclear number. The number of apoptotic nuclei was increased after transection, and exercise attenuated this increase. However, the decrease in apoptotic nuclei with exercise did not significantly affect myonuclear number. We conclude that apoptotic nuclear loss likely contributes to loss of nuclei during muscle atrophy associated with spinal cord transection and that exercise can maintain muscle mass, at least in the short term, without restoration of myonuclear number. <http://www.ncbi.nlm.nih.gov/htbin-po...r&uid=10484346
http://ajpcell.physiology.org/cgi/co...ct/277/3/C589> Department of Geriatrics, University of Arkansas for Medical Sciences, and Central Arkansas Veterans Health Care System, Little Rock, Arkansas 72205, USA.
7. Houle JD, Schramm P and Herdegen T (1998). Trophic factor modulation of c-Jun expression in supraspinal neurons after chronic spinal cord injury. Exp Neurol. 154 (2): 602-11. Summary: Cervical, but not thoracic spinal cord injury upregulates, in certain brainstem neurons, the expression of c-Jun, an inducible transcription factor that may be involved in the regenerative program/cell body response to injury. This study was designed to evaluate changes in c- Jun expression over a long period after spinal cord injury and to determine if such expression could be influenced by trophic or growth factors. Adult rats received a cervical (C3) hemisection lesion. Four or eight weeks later the lesion site was exposed, scar tissue in the cavity was removed and gel foam saturated with ciliary neurotrophic factor (CNTF), basic fibroblast growth factor (FGF2), or phosphate- buffered saline (PBS) as a control was placed into the cavity. Animals were sacrificed 7 days after treatment. In response to axotomy, c-Jun expression remained elevated in the red nucleus (RN) and vestibular complex (VST) at 4 weeks after injury, with no changes observed following scar tissue removal and PBS treatment. In contrast, treatment with CNTF further increased expression by RN neurons, but not VST neurons. Treatment with FGF2 had no significant effect on c-Jun expression at 4 weeks after injury. After 8 weeks, c-Jun expression approached baseline levels; however, removal of scar tissue, with subsequent secondary injury, caused an upregulation of c-Jun expression in both RN and VST neurons, which could be enhanced by CNTF, but not FGF2, treatment. At long postinjury intervals, interventive therapy known to promote axonal regeneration from chronically injured neurons leads to a reinduction of c-Jun expression. This reinduction may be related to the initiation of the regenerative effort of these neurons, although the lack of c-Jun upregulation by certain types of neurons does not appear to prevent a regenerative response by these cells. <http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9878195> Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock, Arkansas, 72205, USA.
8. Dupont-Versteegden EE, Houle JD, Gurley CM and Peterson CA (1998). Early changes in muscle fiber size and gene expression in response to spinal cord transection and exercise. Am J Physiol. 275 (4 Pt 1): C1124-33. Summary: Muscles of spinal cord-transected rats exhibit severe atrophy and a shift toward a faster phenotype. Exercise can partially prevent these changes. The goal of this study was to investigate early events involved in regulating the muscle response to spinal transection and passive hindlimb exercise. Adult female Sprague-Dawley rats were anesthetized, and a complete spinal cord transection lesion (T10) was created in all rats except controls. Rats were killed 5 or 10 days after transection or they were exercised daily on motor-driven bicycles starting at 5 days after transection and were killed 0.5, 1, or 5 days after the first bout of exercise. Structural and biochemical features of soleus and extensor digitorum longus (EDL) muscles were studied. Atrophy was decreased in all fiber types of soleus and in type 2a and type 2x fibers of EDL after 5 days of exercise. However, exercise did not appear to affect fiber type that was altered within 5 days of spinal cord transection: fibers expressing myosin heavy chain 2x increased in soleus and EDL, and extensive coexpression of myosin heavy chain in soleus was apparent. Activation of satellite cells was observed in both muscles of transected rats regardless of exercise status, evidenced by increased accumulation of MyoD and myogenin. Increased expression was transient, except for MyoD, which remained elevated in soleus. MyoD and myogenin were detected both in myofiber and in satellite cell nuclei in both muscles, but in soleus, MyoD was preferentially expressed in satellite cell nuclei, and in EDL, MyoD was more readily detectable in myofiber nuclei, suggesting that MyoD and myogenin have different functions in different muscles. Exercise did not affect the level or localization of MyoD and myogenin expression. Similarly, Id-1 expression was transiently increased in soleus and EDL upon spinal cord transection, and no effect of exercise was observed. These results indicate that passive exercise can ameliorate muscle atrophy after spinal cord transection and that satellite cell activation may play a role in muscle plasticity in response to spinal cord transection and exercise. Finally, the mechanisms underlying maintenance of muscle mass are likely distinct from those controlling myosin heavy chain expression. <http://www.ncbi.nlm.nih.gov/htbin-po...=r&uid=9755066
http://ajpcell.physiology.org/cgi/co...l/275/4/C1124> Department of Geriatrics, University of Arkansas for Medical Sciences, Geriatric Research, Education, Clinical Center, McClellan Department of Veterans Affairs Hospital, Little Rock, Arkansas 72205, USA.
9. Ye JH and Houle JD (1997). Treatment of the chronically injured spinal cord with neurotrophic factors can promote axonal regeneration from supraspinal neurons. Exp Neurol. 143 (1): 70-81. Summary: Axonal regeneration has been demonstrated by supraspinal neurons long after a spinal cord injury, although this potential seems limited to a few neurons in specific nuclear groups. Whether the regenerative response could be enhanced by exposure to neurotrophic factors was examined in this study. Neurons injured during a cervical spinal cord hemisection lesion were labeled with true blue (TB). Four weeks after spinal cord injury, gel foam saturated with brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), ciliary neurotrophic factor (CNTF), or saline as a control was placed into the lesion cavity. The gel foam was replaced with fresh factor after 3 days, and 4 days later a peripheral nerve (PN) graft was apposed to the rostral cavity wall. Four weeks later neurons that grew an axon into the PN graft were labeled with nuclear yellow (NY). Cells that were double labeled (TB and NY) represented chronically injured neurons capable of axon regeneration. Cells labeled with NY only were either acutely injured neurons capable of axonal regrowth or uninjured neurons that had sprouted into the PN graft. The total number of TB/NY-labeled neurons was significantly increased following exposure to BDNF, NT-3, or CNTF. Specific regions most influenced by NT-3 and BDNF were the reticular formation and red nucleus. Treatment with CNTF resulted in a significant increase in most brain regions with a major contribution to descending pathways in the spinal cord, the motor cortex being the exception, with no evidence of axonal regeneration by neurons forming the corticospinal tract. The total number of NY-only labeled neurons also was significantly greater after treatment with BDNF or CNTF. These results demonstrate the potential to increase the regenerative response of specific chronically injured supraspinal neurons by application of neurotrophic factors to the injury site. <http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9000447> Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
10. Skinner RD, Houle JD, Reese NB and Garcia-Rill EE (1997). Electrophysiological investigations of neurotransplant-mediated recovery after spinal cord injury. Adv Neurol. 72: 277-90. Summary: <http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8993705> Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
11. Prewitt CM, Niesman IR, Kane CJ and Houle JD (1997). Activated macrophage/microglial cells can promote the regeneration of sensory axons into the injured spinal cord. Exp Neurol. 148 (2): 433-43. Summary: A prominent role for phagocytic cells in the regenerative response to CNS or PNS injury has been suggested by numerous studies. In the present work we tested whether increasing the presence of phagocytic cells at a spinal cord injury site could enhance the regeneration of sensory axons from cut dorsal roots. Nitrocellulose membranes treated with TGF-beta or coated with microglial cells were cotransplanted with fetal spinal cord tissue into an injured adult rat spinal cord. Cut dorsal roots were apposed to both sides of the nitrocellulose. Four weeks later, animals were sacrificed and spinal cord tissue sections were processed for immunocytochemical detection of calcitonin gene- related peptide (CGRP-ir) to identify regenerated sensory axons. Adjacent sections were processed with the antibody ED-1 or the lectin GSA-B4 for detection of macrophage/microglial cells in association with the regrowing axons. Qualitative and quantitative data indicate a correlation between the pattern and extent of axonal regeneration and the presence of phagocytic cells along the nitrocellulose implant. Axonal regeneration could be experimentally limited by implanting a nitrocellulose strip treated with macrophage inhibitory factor. These results indicate that increasing the presence of activated macrophage/microglial cells at a spinal cord injury site can provide an environment beneficial to the promotion of regeneration of sensory axons, possibly by the release of cytokines and interaction with other nonneuronal cells in the immediate vicinity. <http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9417823> Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
12. Houle JD and Ziegler MK (1994). Bridging a complete transection lesion of adult rat spinal cord with growth factor-treated nitrocellulose implants. J Neural Transplant Plast. 5 (2): 115-24. Summary: The ability of a substrate bound neurotrophic factor to promote growth of ascending sensory axons across a complete transection lesion of the rat spinal cord was examined in a transplantation model. Aspiration lesions created a 3 mm long cavity in the upper lumbar spinal cord of adult rats. Five weeks after injury two strips of nerve growth factor- treated nitrocellulose were implanted, each in a medio-lateral position, and apposed to the rostral and caudal surfaces of the cavity. Control animals received untreated nitrocellulose implants. Fetal spinal cord tissue was transplanted alongside and between these strips. Six weeks post transplantation, animals were sacrificed and vibratome sections through the grafts were processed for immunocytochemical demonstration of ingrowing axons expressing calcitonin gene-related peptide (CGRP-IR). Immunolabeled axons were abundant at the caudal interface between host tissue and the NGF-treated nitrocellulose implants, with dense fascicles of fibers abutting the grafts. As the distance from the caudal surface increased some CGRP-IR fibers extended into the fetal tissue although most appeared to remain oriented in a longitudinal course adjacent to the nitrocellulose. Labeled axons were evident along the entire length of the nitrocellulose and appeared to aggregate at the rostral tip of the implant, with many fibers extending into the host spinal cord rostral to the lesion/transplant site. When untreated nitrocellulose was implanted, fewer labeled axons appeared to extend beyond the caudal host-graft interface. Most CGRP-IR axons displayed limited association or contact with the untreated nitrocellulose in this condition. Computer-assisted quantitative analysis indicated that NGF-treated nitrocellulose supported regrowing host axons for nearly three times the length exhibited by axons associated with non-treated nitrocellulose implants. These results indicate that substrate bound nerve growth factor has the capacity to enhance the regrowth of ascending sensory axons across a traumatic spinal cord injury site. The potential to reestablish functional contacts across such a lesion may be heightened by the ability of neurotrophic factors to promote more extensive axonal regrowth. <http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=7703291> Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock 72205.
13. Houle J (1992). The structural integrity of glial scar tissue associated with a chronic spinal cord lesion can be altered by transplanted fetal spinal cord tissue. J Neurosci Res. 31 (1): 120-30. Summary: The potential for fetal spinal cord (FSC) tissue transplants to modify an established glial scar or to restrict the reformation of a scar following surgical manipulation of a chronic lesion site was studied in the injured rat spinal cord. Six to eight weeks after preparation of a hemisection lesion cavity, glial scar tissue was left intact in one group, whereas in a second group it was excised prior to transplantation of a suspension of FSC tissue. From the first group, examination of serial sections through the graft-host interface that had been immunoreacted for glial fibrillary acidic protein (GFAP) demonstrated that in many cases the glial scar no longer was a continuous wall separating the two tissues. Quantitation of the area occupied by these discrete gaps in the scar provided an Index of Fusion, indicating the extent of direct contact between the transplant and host spinal cord. In some animals this constituted as much as 60% of the interface, while in others there were no breaks in the scar (0% fusion). Reinjury of the spinal cord lead to a rapid astrocytic response culminating in the reestablishment of a dense matrix of glial cells and processes covered by a basal lamina. This reformed scar effectively isolated the spinal cord from the external environment of the cavity. When FSC tissue was transplanted after first removing scar tissue the continuity of reformed glial scarring at the graft-host interface was altered. Distinct gaps in the scar appeared randomly along the interface. The mean Index of Fusion for animals receiving a moderate reinjury (removal of scar tissue only) was not as high as for those animals in which a more severe reinjury (expansion of the cavity by 0.5 mm) was performed before transplantation. The extent of graft- host fusion was not significantly improved when scar tissue was removed prior to transplantation. These findings support the hypothesis that the presence of FSC tissue will have an effect on the persistence of glial scar tissue in a chronic lesion site as well as limit the extent to which a new scar is formed in response to a second injury to the spinal cord. <http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=1613818> Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock 72205.
14. Houle JD (1991). Demonstration of the potential for chronically injured neurons to regenerate axons into intraspinal peripheral nerve grafts. Exp Neurol. 113 (1): 1-9. Summary: Experiments were carried out to determine if neurons damaged by injury to the spinal cord retain the ability to regenerate their axonal process for a prolonged period of time after the initial response to injury and if peripheral nerve (PN) grafts could support the regrowth of these processes. True blue (TB) was injected into one side of the adult rat lumbar spinal cord to label neurons with axons coursing through this region. Seven days later spinal cord tissue surrounding the injection sites was removed by aspiration to create a hemisection cavity 3-4 mm in length. Four weeks later scar tissue lining the lesion cavity was removed prior to grafting 1 cm segments of autologous tibial nerve to the rostral and the caudal surfaces of the cavity wall. The distal end of each graft was ligated and left unapposed to spinal cord tissue. Four weeks later the distal end of each PN graft was exposed to nuclear yellow (NY) to retrogradely label neurons that had grown an axon into the graft. Neurons containing both TB and NY were deemed capable of axonal regeneration while in a chronically injured state. Double-labeled (TB/NY) neurons were found in the ipsilateral spinal cord in laminae IV through X, excluding IX, and in Laminae VI and VII contralateral to the lesion. Most neurons were located within 10 mm of the lesion, with the majority caudal to the lesion. Nearly 50% (range 24-74%) of lumbar dorsal root ganglion neurons containing TB also were labeled with NY.(ABSTRACT TRUNCATED AT 250 WORDS). <http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=2044676> Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock 72205.
15. Houle JD and Reier PJ (1989). Regrowth of calcitonin gene-related peptide (CGRP) immunoreactive axons from the chronically injured rat spinal cord into fetal spinal cord tissue transplants. Neurosci Lett. 103 (3): 253-8. Summary: Fetal spinal cord tissue was transplanted into either a hemisection or complete transection lesion site at lumbar levels of the adult rat spinal cord that had been produced 3, 6, or 11 weeks prior to grafting. Tissue sections containing the graft and adjacent regions of the host spinal cord were processed for calcitonin gene-related peptide immunoreactivity (CGRP-IR) 2-6 months later. Numerous CGRP-IR axons within laminae I, II, V and X of the host spinal cord were observed crossing the graft-host interface as they spread diffusely throughout the caudal-rostral extent of the transplants. Many of these immunolabeled axons terminated in a distinct bouton-like formation. These results indicate that within the chronically injured spinal cord at least one-specific neuronal population retains the potential for regrowth in a long-term injury condition and that this capacity for axonal elongation can be sustained by the presence of fetal spinal cord tissue grafts. <http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=2682392> Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock 72205.
16. Tessler A, Himes BT, Houle J and Reier PJ (1988). Regeneration of adult dorsal root axons into transplants of embryonic spinal cord. J Comp Neurol. 270 (4): 537-48. Summary: Transplants of the embryonic rat spinal cord survive and differentiate in the spinal cords of adult and newborn host rats. Very little is known about the extent to which these homotopic transplants can provide an environment for regeneration of adult host axons that normally terminate in the spinal cord. We have used horseradish peroxidase injury filling and transganglionic transport methods to determine whether transected dorsal roots regenerate into fetal spinal cord tissue grafted into the spinal cords of adult rats. Additional transplants were examined for the presence of calcitonin gene-related peptide-like immunoreactivity, which in the normal dorsal horn is derived exclusively from primary afferent axons. Host animals had one side of the L4-5 spinal cord resected and replaced by a transplant of E14 or E15 spinal cord. Adjacent dorsal roots were sectioned and juxtaposed to the graft. The dorsal roots and their projections into the transplants were then labeled 2-9 months later. The tracing methods that used transport or diffusion of horseradish peroxidase demonstrated that severed host dorsal root axons had regenerated and grown into the transplants. In addition, some donor and host neurons had extended their axons into the periphery to at least the midthigh level as indicated by retrograde labeling following application of tracer to the sciatic nerve. Primary afferent axons immunoreactive for calcitonin gene-related peptide were among those that regenerated into transplants, and the projections shown by this immunocytochemical method exceeded those demonstrated by the horseradish peroxidase tracing techniques. Growth of the host dorsal roots into transplants indicates that fetal spinal cord tissue permits regeneration of adult axotomized neurons that would otherwise be aborted at the dorsal root/spinal cord junction. This transplantation model should therefore prove useful in studying the enhancement and specificity of the regrowth of axons that normally terminate in the spinal cord. <http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=3259590> Department of Anatomy, Medical College of Pennsylvania, Philadelphia 19129.
17. Reier PJ, Houle JD, Jakeman L, Winialski D and Tessler A (1988). Transplantation of fetal spinal cord tissue into acute and chronic hemisection and contusion lesions of the adult rat spinal cord. Prog Brain Res. 78: 173-9. Summary: <http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=3247421>
18. Reier PJ and Houle JD (1988). The glial scar: its bearing on axonal elongation and transplantation approaches to CNS repair. Adv Neurol. 47: 87-138. Summary: <http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=3278533> Department of Neurological Surgery, J. Hillis Miller Health Center, University of Florida College of Medicine, Gainesville 32610.
19. Houle JD and Reier PJ (1988). Transplantation of fetal spinal cord tissue into the chronically injured adult rat spinal cord. J Comp Neurol. 269 (4): 535-47. Summary: Transplants of fetal central nervous system (CNS) tissue into the acutely injured rat spinal cord have been demonstrated to differentiate and partially integrate with the adjacent host neuropil. In the present study, we examined the potential for applying a transplantation approach to chronic spinal cord lesions. In particular, we were interested in learning whether host-graft fusion would be adversely affected by an advanced histopathology characterized in part by glial scar formation. Hemisection cavities were prepared at lumbar levels of the adult rat spinal cord 2-7 weeks prior to the transplantation of spinal cord tissue obtained from 14-day rat fetuses. Graft survival, differentiation, and integration with the host spinal cord were subsequently evaluated by light microscopic techniques at post- transplantation intervals of 1-6 months. Immunocytochemistry was also employed to examine the extent of astrocytic scar formation at the host- graft interface and serotoninergic innervation of the grafts. In some other cases, anterograde and retrograde transport of wheat germ agglutinin-conjugated horseradish peroxidase was used to determine whether axonal projections were formed between the host spinal cords and grafts. By 2 weeks after injury the initial lesion cavities were surrounded by a continuous astrocytic scar which remained intact for at least 7 weeks after injury in nongrafted control animals. In other animals, transplantation into these advanced lesions resulted in well- differentiated grafts with a 90% long-term survival rate. Although dense gliosis was still present along the lesion surfaces of the recipient spinal cord, foci of confluent host-graft neuropil were observed where interruptions in the scar had occurred. Donor tissue integrated most often with the host spinal cord at interfaces with host gray matter; however, some implants also exhibited sites of fusion with damaged host white matter. Thus, some regions of confluent graft and host neuropil could be routinely identified, despite the presence of a dense glial scar along the walls of the chronic lesion site at the time of transplantation. Anterograde and retrograde tract-tracing results suggested that some axonal projections into these grafts had originated from host neurons located immediately adjacent to the donor-recipient interface. In addition, immunocytochemistry revealed some host serotoninergic axons (presumably of supraspinal origin) traversing nongliotic interfaces. The results of this study raise the possibility that grafted fetal CNS tissue has a capacity for stimulating partial regression of an established glial scar.(ABSTRACT TRUNCATED AT 400 WORDS). <http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=2453536> Department of Neurological Surgery, College of Medicine, University of Florida, Gainesville 32610.