CNS Axon Regeneration in the Long Primary Afferent System in E15/E16 Hypoxic-Conditioned Fetal Rats: A Thrust-Driven Concept
Abstract
1. Introduction
2. Materials and Methods
2.1. A Summary
1 | 2 | 3 | 1 | 2 | 3 |
---|---|---|---|---|---|
Case ID | litter-ratio | Figure | Case ID | litter-ratio | Figure |
(Tx: n = p0) | (Tx: n = p0) | ||||
C39.E18.E20 | N/A | T47.E16.p4 | (1:2 = 2) | ||
C44.Sx.p4 | N/A | T60.E16+12h.p135 | (1:10 = 10) | ||
D14.D5.E21 | N/A | T62.E16.5.p17 | (2:11 = 11) | ||
D15.E17.E20 | N/A | T65.E16.5.p48 | (1:10 = 10) | ||
D20.D17.E18 | N/A | T68.E16.5.p370 | (1:11 = 11) | ||
N45.E17.p8 | (1:4 = 4) | T77.E17.p35 | (1:12 = 12) | ||
N46.E18.p10 | (2:15 = 15) | T78.E16+2h.p40 | (1:8) = 7 | Figure 3 | |
P1.E18.p48 | (2:15 = 14 + 1 †) | V1.E16+6h.p600 | (1:10 = 9) | Figure 5 | |
P17.E17.p90 | (2:10 = 10) | V2.E16-1h.p240 | (2:14 = 13) | ||
P20.E18.p600 | (2:9 = 8) | V3.E16-1h.p195 | (1:13 = 12 + 1 †) | ||
R9.s6.E17.p44 | (4:11 = 11) | V31.E16-3h.p145 | (1:13 = 13) | ||
T8.E17.p180 | (2:15 = 15) | V38.E16-3h.p210 | (1:15 = 15) | ||
T9.2.E18.p225 | (3:15 = 12) | V51.E16-4h.p2 | (1:9 = 9) | ||
T12.E17.p7 | (2:15 = 15) | V63.E16-2h.p1.5 | (1:11 = 11) | ||
T13.E17.p7 | (2:14 = 12) | V67.E16+7h.p9 | (1:7 = 7) | ||
T15.E17.p305 | (3:16 = 14) | V72.E16+8h.p1.5 | (1:14 = 14) | ||
T16.E17.p40 | (2:15 = 13) | W2.E16-7h.p9 | (2:10 = 10) | Figure 6A,D | |
T20.E17.p700 | (1:9 = 7) | W2.E16-6.5h.p42 | (2:10 = 10) | Figure 6E,H | |
T23.E16.p360 | (1:6 = 6) | W6.E16.p32 | (2:14 = 14) | ||
T34.E17.p100 | (1:8 = 8) | W14.E16-8h.p14 | (2:15 = 15) | Figure 8 | |
T42.E16.p240 | (1:9 = 9) | Figure 4 | W17.E16.p64 | (1:14 = 14) | |
T45.E16.p7 | (1:4 = 4) | W20.E16-9h.p6 | (2:11 = 9) | Figure 7 | |
T46.E16.p3 | (1:13 = 12 + 1 †) |
2.2. Preamble to the Long Primary Afferent System’s Development
2.3. The Impact of Hypoxia During the Critical Period
2.4. The Watershed: Axons Share the Critical Period Restricting Intrinsic Regeneration
3. Results
3.1. Regeneration Comes to a Halt Before Neap Tide
3.2. Six Bell Ringer Cases Exhibiting All Dynamic Features
* | asterisk | a single asterisk indicates a TH.1 i-FS | ||||||
** | asterisks | a tandem asterisk indicates a TH.2 i-FS | ||||||
*** | asterisks | three asterisks indicate downstream TH.3 colls | ||||||
g.nu | gracile nucleus | |||||||
4th V | fourth ventricle | |||||||
L|Th|C | Lumbar|Thoracic|Cervical segment of the spinal cord | |||||||
c <== ==> r | caudal <== ==> rostral direction of the spinal cord | |||||||
d <== ==> v | dorsal <== ==> ventral in a sagittal section of the spinal cord | |||||||
L/R | left side/right side | of the spinal cord in a horizontal section | ||||||
N | fix pinhole | an artifact from tissue processing; a number identifies the spinal cord’s level derived from the gelatine block’s count | ||||||
spinal level of Tx | ||||||||
depicted level in the Figure |
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Glossary
a-FS | abrupt front stop | A bundle of WM-facing i-FSs manifests in neonates. The a-FS abuts the rostral lesion site, and the phenotype demonstrates the blocked development [12] |
CP | critical period | Upstream time slot(s) delineating elongation in each (and all) pioneering long primary afferent axon(s), as well as axon regeneration |
CG | central gray | neuropil |
colls | TH.3-staged collaterals = collateral sprouting after the TH.3 transit. They confirm accomplished development, e.g., in gracile nuclei | |
DRG | dorsal root ganglion | involving the lumbar segments L4, L5, and L6 (HRP-tracing at the left side, only) |
DC | dorsal column | |
E16-8h | 15th day of gestation | M0 is scheduled 15 days + 16 h after mating, restricted to 1 h |
E16 | day of conception without surveillance of mating time | |
f-ES | fast elongation stop | a hypothetical phenomenon of pioneering TH.0-staged axons arriving at the medulla and swiftly slowing down |
fringe | The CG adjacent to the DC white matter | |
high tide | In the rostral DC, pioneering axons target the gracile nuclei in high-tide waves at spring tide | |
i-FS | intrinsic front stop | The hypothetical TH.1- and TH.2-stage axon mimicries generate phenotypes, which demonstrate blocked development. At high tide, the i-FSs regenerate toward the medulla. At low tide, the TH.1 fiber tips remain caudally distanced from the lesion site, while the TH.2 i-FSs terminate caudally in the lesion site. |
HRP | Horseradish peroxidase | |
low tide | In the lower thoracic DC, pioneering axons target Clarke’s nucleus in low-tide waves at neap tide Horseradish peroxidase | |
M0 | The moment of Tx is referenced to the hour (or day) of conception and serves as the case ID in combination with survival time (Table 1). M0 has a temporospatial link with a location on the assembly line determined by the axon features, demonstrating variability. This underlines that the development of fetuses is prone to differ | |
neap tide | See low tide | |
s-ES | slow elongation switch | The hypothetical phenomenon of TH.1 axons transitioning into the consecutive TH.2 stage |
spring tide | See high tide | |
tc | Terminal club: fiber termination with a configuration comparable to i-FS | |
THs | transition hubs | TH.0, TH.1, TH.2, and TH.3 are hypothetical transition hubs situated on the developmental cascade. TH.0 axons were reprogrammed into the TH.1 i-FS mimicry, and TH.1 into the TH.2 i-FS substitute |
TH.0 | staged axon | Pioneering primary afferent axon in a high-tide, as well as a low-tide wave |
Tx | dorsal myelotomy | The microsurgical procedure |
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de Beer, F.C.; Steinbusch, H.W.M. CNS Axon Regeneration in the Long Primary Afferent System in E15/E16 Hypoxic-Conditioned Fetal Rats: A Thrust-Driven Concept. Anatomia 2025, 4, 12. https://doi.org/10.3390/anatomia4030012
de Beer FC, Steinbusch HWM. CNS Axon Regeneration in the Long Primary Afferent System in E15/E16 Hypoxic-Conditioned Fetal Rats: A Thrust-Driven Concept. Anatomia. 2025; 4(3):12. https://doi.org/10.3390/anatomia4030012
Chicago/Turabian Stylede Beer, Frits C., and Harry W. M. Steinbusch. 2025. "CNS Axon Regeneration in the Long Primary Afferent System in E15/E16 Hypoxic-Conditioned Fetal Rats: A Thrust-Driven Concept" Anatomia 4, no. 3: 12. https://doi.org/10.3390/anatomia4030012
APA Stylede Beer, F. C., & Steinbusch, H. W. M. (2025). CNS Axon Regeneration in the Long Primary Afferent System in E15/E16 Hypoxic-Conditioned Fetal Rats: A Thrust-Driven Concept. Anatomia, 4(3), 12. https://doi.org/10.3390/anatomia4030012