Unequivocal Regeneration of Rat Optic Nerve Axons into Sciatic Nerve Isografts

Berry, Martin; Rees, L.; Sievers, Jobst

doi:10.1007/978-1-4612-4846-0_2

Cited by 15 publications

(17 citation statements)

References 40 publications

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“…Neurons in the central nervous system (CNS) of adult mammals cannot normally regenerate their axons following injury, but it is now well established that axotomised CNS neurons can regenerate axons for long distances through segments of peripheral nerve implanted into the brain or spinal cord or attached to the retinal stump of severed optic nerves (David and Aguayo, 1981;Benfey et al, 1985;Aguayo, 1985;Berry et al, 1986). Not all populations of CNS neurons show the same propensity for axonal regeneration.…”

Section: Indexing Terms: Axotomy; Cns Regeneration; Nerve Graft; Cellmentioning

confidence: 99%

The cell recognition molecule CHL1 is strongly upregulated by injured and regenerating thalamic neurons

et al. 2000

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Close homologue of L1 (CHL1) is a cell recognition molecule known to promote axonal growth in vitro. We have investigated the expression of CHL1 mRNA by regenerating central nervous system (CNS) neurons, by using in situ hybridisation 3 days to 10 weeks following the implantation of living and freeze-killed peripheral nerve autografts into the thalamus of adult rats. At all survival times after implantation of living grafts, neurons of the thalamic reticular nucleus (TRN), close to the graft tip and up to 1 mm away from it, displayed strong signal for CHL1 mRNA, even though TRN neurons show very low levels of CHL1 mRNA expression in unoperated animals. When the cell bodies of regenerating neurons were identified by retrograde labelling from the distal portion of the grafts, 4-6 weeks after operation, most of the labelled cells were found in the TRN and could be shown to haveupregulated CHL1 mRNA. In addition, some neurons in dorsal thalamic nuclei near the graft tip transiently upregulated CHL1 mRNA during the first 3 weeks after graft implantation, and glial cells showing CHL1 mRNA expression were present at the brain/graft interface 3 days to 2 weeks after operation. Freeze-killed grafts, into which axons do not regenerate, caused a transient upregulation of CHL1 in very few TRN neurons near the graft tip and in glial cells at the brain/graft interface but did not produce prolonged CHL1 mRNA expression. CHL1 can therefore be added to the list of molecules (including GAP-43, L1, and c-jun) strongly expressed by CNS neurons that regenerate their axons into nerve grafts, but not by those neurons that fail to regenerate their axons.

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Section: Indexing Terms: Axotomy; Cns Regeneration; Nerve Graft; Cellmentioning

confidence: 99%

The cell recognition molecule CHL1 is strongly upregulated by injured and regenerating thalamic neurons

et al. 2000

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“…Several studies have documented the intrinsic ability of retinal ganglion cells (RGC) of adult rodents to respond to injury with formation of a growth cone and to elongate within the permissive and supporting environment of a grafted piece of an autologous peripheral nerve (PN) (Aguayo, 1985;So and Aguayo, 1985;Berry et al, 1986;Politis and Spencer, 1986;Vidal-Sanz et al, 1987;Thanos, 1988;Carter et al, 1989;Keirstead et al, 1989;Thanos et al, 1993). The PN pieces subserve at least three relevant functions: (1) They provide a permissive biological substrate for axonal growth (Aguayo, 1985).…”

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confidence: 99%

Type-specific stabilization and target-dependent survival of regenerating ganglion cells in the retina of adult rats

Thanos

Mey

1995

J. Neurosci.

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Axotomy-induced degradation of retinal ganglion cells (RGC) can be delayed if the destructive features of activated microglial cells are pharmacologically neutralized, and prevented if the axons are permitted to regrow into transplanted autologous peripheral nerve (PN) pieces. This study was undertaken to classify the regenerating rat RGC and to examine target-dependent effects on survival of subsets of neurons. In analogy to the normal rat retina, we have categorized the retrogradely labeled, regenerating RGC into five classes which are morphologically distinct and reminiscent of normal RGC correlates (types I, II, III, delta-cells, and displaced RGC). Six weeks after transplantation of peripheral nerve to the transected optic nerve, large, type I-like cells (RI) constituted 5.7 +/- 2.0% of the total population. Smaller, round to oval cells of type RII represented the majority of labeled neurons (64.5 +/- 6.1%). Cells of type RIII constituted 4.6 +/- 1.7% of the total population and had very typical, middlesized, polarized perikarya and large dendrites. Less frequent (< 1%) were R-delta and displaced RGC. Transplantation of a PN graft which was not reconnected with a central target (blind-ending group) and monitoring of the extant neurons showed a progressive disappearance of the regenerating RGC, such that 6 months after surgery predominantly few large cells survived. When the retinas were treated with macrophage/microglia- inhibiting factor (MIF), and the regenerating axons were guided into the pretectum, predominantly large RGC of type RI survived. Guidance of the axons into their major natural target, the superior colliculus (SC), resulted in selective survival of many small, RII-like RGC. Calculation of the dendritic coverage factors for the major types of RGC revealed that dendrites of the most abundant small cells of type RII overlapped uniformly and covered the retinal surface completely, whereas cells of types RI and RIII did not suffice for surface coverage. The results suggest that combined suppression of axotomy- induced microglial activation and guidance of regenerating axons with a PN graft into central targets is a suitable technique to produce sufficient numbers of regenerating axons which may retrieve some functional properties. Target-specific neuronal contacts are likely involved in morphological stabilization and better survival of regenerating neurons.

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“…Nigrostriatal axons are nonmyelinated (Hattori et al, 1973) and were the most consistently successful axons at regenerating in the present study. However, the axons of retinal ganglion cells are almost entirely myelinated within the optic nerve, yet they produce many regenerative axonal sprouts after injury (Hall and Berry, 1989;Zeng et al, 1994) and regenerate vigorously into peripheral nerve grafts (So and Aguayo, 1985;Berry et al, 1986). Another explanation of the differential regeneration of CNS axons is that there are differences between neurons in the intrinsic determinants of axonal growth.…”

Section: Mechanisms Of Differential Regenerative Axonal Growthmentioning

confidence: 96%

“…It is now widely accepted that living peripheral nerve tissue implanted into the brain, spinal cord, or primary visual pathway can promote the regeneration of axons from central nervous system (CNS) neurons (Aguayo, 1985;Berry et al, 1986). However, it is much less well appreciated that CNS neurons differ in their ability to respond to such grafts and that not all populations of CNS neurons are able to mount an effective regenerative response to injury, even in the presence of a peripheral nerve graft.…”

mentioning

confidence: 99%

Differential effects of autologous peripheral nerve grafts to the corpus striatum of adult rats on the regeneration of axons of striatal and nigral neurons and on the expression of GAP-43 and the cell adhesion molecules N-CAM and L1

et al. 1998

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A segment of tibial nerve was autografted to the right corpus striatum of deeply anesthetized adult rats; the distal graft was left beneath the scalp. Horseradish peroxidase (HRP) conjugates were injected into the distal graft after 2-30 weeks, and the animals were killed 2-3 days later. Small numbers of neostriatal perikarya were HRP labeled at all survival times; most were large (ca. 20 microm in diameter), and many contained acetycholine esterase (AChE). Many more neurons were labelled in the substantia nigra pars compacta (SNpc) 4 weeks or more after grafting. When the graft encroached on the globus pallidus, numerous pallidal neurons, most of them AChE positive, were also labeled. Nigrostriatal neurons, a population of pallidal cholinergic neurons, and a subclass (or classes) of neostriatal neurons, including cholinergic interneurons, thus can be classified as central nervous system (CNS) neurons with a relatively strong regenerative response. In a second experimental series, animals were killed 1-4 weeks after grafting, and sections were probed for the expression of mRNAs encoding growth-associated protein 43 (GAP-43) and the cell adhesion molecules N-CAM and L1. Subpopulations of mostly large neurons scattered throughout the neostriatum gave moderate signals for GAP-43 and N-CAM mRNAs and a stronger signal for L1 mRNAs. Most SNpc neurons were strongly labeled with all three probes. Neostriatal grafts had no apparent effect on the expression of any of the mRNAs in the SNpc or on L1 and N-CAM mRNAs in the striatum. However, GAP-43 mRNA levels were increased in a few, mainly large neostriatal neurons around the graft tip, resembling the HRP-labeled cells. In contrast, previous work has shown upregulation (from an undetectable level) of GAP-43 and L1 mRNAs in neurons regenerating axons into grafts placed in the thalamus and cerebellum. Thus, GAP-43 and L1 mRNA expression, but not necessarily marked upregulation, may correlate with, and be intrinsic determinants of, the ability of CNS neurons to regenerate their axons.

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Unequivocal Regeneration of Rat Optic Nerve Axons into Sciatic Nerve Isografts

Cited by 15 publications

References 40 publications

The cell recognition molecule CHL1 is strongly upregulated by injured and regenerating thalamic neurons

The cell recognition molecule CHL1 is strongly upregulated by injured and regenerating thalamic neurons

Type-specific stabilization and target-dependent survival of regenerating ganglion cells in the retina of adult rats

Differential effects of autologous peripheral nerve grafts to the corpus striatum of adult rats on the regeneration of axons of striatal and nigral neurons and on the expression of GAP-43 and the cell adhesion molecules N-CAM and L1

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