Retrograde Regeneration Research Articles

Pectoralis Major Reinnervation by Retrograde Nerve Regeneration after Complete Paralysis of the Brachial Plexus.

Spontaneous neuronal recovery is an expected phenomenon in brachial plexus palsy patients. However, the spontaneous recovery owing to retrograde regeneration is an evolving phenomenon with dearth of adequate research on it. Pectoralis major contraction on stimulation of median nerve (in the arm) is an unexpected phenomenon, in the absence of any anomalous communication and with distal coaptation site of intraplexal nerve repair. We presumably attribute it to the retrograde regrowth of axons. The case described supports our hypothesis. Level of Evidence: Level V (Therapeutic).

Successful retrograde regeneration using a sensory branch for motor nerve transfer.

The objective of this study was to test whether regenerating motor axons from a donor nerve can travel in a retrograde fashion using sensory branches to successfully reinnervate a motor nerve end organ. This study has two parts. In part I, rats (n = 30) were assigned to one of five groups for obturator nerve (ON)-to-femoral nerve transfer: group 1, ON-to-saphenous nerve (SN) distal stump; group 2, ON-to-SN proximal stump without femoral nerve proper (FNP) injury; group 3, ON-to-SN proximal stump with FNP crush injury; group 4, ON-to-SN proximal stump with FNP transection injury; and group 5, gold standard transfer, ON-to-motor femoral nerve (MFN) branch. At 8 weeks, retrograde labeling was done from the distal MFN, and the spinal cords were examined to assess the degree of obturator motor axon regeneration across the five groups. In part II, only group 4 was examined (n = 8). Through use of immunostaining and optical tissue clearing methods, the nerve transfer networks were cleared and imaged using light-sheet fluorescence microscopy to visualize the regeneration pathways in 2D and 3D models at 2- and 8-week time points. Proximal FNP transection (group 4) enabled a significantly higher number of retrogradely regenerated motor axons compared with control groups 1-3. Moreover, group 4 had modest, but nonsignificant, superiority of motor neuron counts compared with the positive control group, group 5. Optical tissue clearing demonstrated that the axons traveled in a retrograde fashion from the recipient sensory branch to the FNP mixed stump, then through complex turns, down to distal branches. Immunostaining confirmed the tissue clearing findings and suggested perineurium disruption as a means by which axons could traverse across fascicular boundaries. Sensory branches can transmit regenerating axons from donor nerves back to main mixed recipient nerves, then distally toward target organs. The extent of retrograde regeneration is markedly influenced by the type and severity of injury sustained by the recipient nerve. Using a sensory branch as a bridge for retrogradely regenerating axons can open new potential horizons in nerve repair surgery for severely injured mixed nerves.

Initiation and development of a mesoscale convective system in the Ebro River Valley and related heavy precipitation over northeastern Spain during HyMeX IOP 15a

During Intensive Observation Period 15a (20 October 2012) of the first Special Observation Period of the Hydrological cycle in the Mediterranean Experiment, northeastern Spain experienced heavy precipitation (130 mm in 24 h) associated with a retrograde regeneration mesoscale convective system (MCS) developing in the exit region of the Ebro River Valley (ERV). The life cycle of the MCS that brought intense hourly rainfall (34 mm) from the foothills of the Iberian Plateau to the central Pyrenees, as well as the detailed structure of the moist marine flow upstream, were analysed using a combination of ground‐based, airborne and space‐borne observations as well as model analyses. Over the Balearic Sea, the southwesterlies along the northeastern flank of a surface low converged with southeasterlies from North Africa, creating a near‐surface moisture tongue in the region of the Balearic Islands, and a southeast–northwest oriented convergence line within a cloud cluster advecting from northern Africa. Airborne lidar measurements, acquired upstream of the ERV, evidenced water vapour mixing ratios in excess of 15 g kg−1 in the marine atmospheric boundary layer. In the mid‐level (700 hPa), the presence of an elevated moisture plume from tropical Africa contributed about one third to the large moisture content present over the western Mediterranean Sea. In this moist environment, the MCS was initiated over the orography of the northeastern tip of the Iberian plateau, due to the combined influence of the approaching convergence line ahead of the surface low and the convergence resulting from weak northwesterlies channelled in the ERV and the easterlies impinging on the coastal range. After the initiation phase, the MCS further developed over the foothills of the Iberian Plateau and moved into the ERV and along the southern flank of the Pyrenees, thanks to the penetration of the warm and moist maritime southeasterly flow through the narrow gap between the northeastern part of the Iberian Plateau and the Catalan coastal range.

Convective initiation and maintenance processes of two back‐building mesoscale convective systems leading to heavy precipitation events in Southern Italy during HyMeX IOP 13

During Intensive Observation Period 13 (15 to 16 October 2012) of the first Special Observing Period of the Hydrological cycle in the Mediterranean Experiment (HyMeX), Southern Italy (SI) was affected by two consecutive heavy precipitation events (HPEs). Both HPEs were associated with multi‐cell V‐shaped retrograde regeneration mesoscale convective systems (MCSs). The life cycle of two MCSs in connection with their dynamic and thermodynamic environments were analysed using a combination of ground‐based, airborne and spaceborne observations and numerical simulations. Rain gauges revealed that heavy precipitation occurred in two phases: the first one from 1300 to 1700 UTC (35 mm h−1) was caused by a V‐shaped system initiating over the Tyrrhenian Sea in the early morning of 15 October. Convection was triggered by the low‐level convergence between the southwesterlies ahead of an upper‐level trough positioned over southeastern France and very moist southerlies from the Strait of Sicily. The convection was favoured by high convective available potential energy (1500 J kg−1) resulting from warm and moist conditions at low levels associated with high sea surface temperatures in the Strait of Sicily. In addition, humidity at mid‐level was enriched by the presence of an elevated moisture plume from tropical Africa, favouring the efficiency of the convection to produce more precipitation. The second phase of heavy precipitation (2300 UTC on 15 October to 0200 UTC on 16 October, 34 mm h−1) was caused by a MCS initiating over Algeria around 1300 UTC, which subsequently travelled over the Strait of Sicily toward Sicily and SI. Convection was maintained by the combination of large low‐level moisture contents and a marked convergence ahead of the cold front. Unlike other MCSs forming in the same region earlier on that day, this huge V‐shaped system did affect SI because the strong upper‐level flow progressively backed from southwesterly to south southwesterly.

Sensing nerve injury at the axonal ER: activated Luman/CREB3 serves as a novel axonally synthesized retrograde regeneration signal.

Luman/cAMP response element binding protein 3 is an endoplasmic reticulum (ER) transmembrane basic leucine zipper transcription factor whose mRNA and protein localize to adult sensory axons, the latter with axonal ER components along the axon length. Here we show that axon-derived Luman plays an important role in relaying information about axonal injury to the neuronal cell body. Axotomy induces axonal Luman synthesis and also release from the axonal ER of Luman's transcriptionally active amino terminus, which is transported to the cell body in an importin-mediated manner. Visualization of the activation and retrograde translocation of Luman into the nucleus in real time both in vivo and in vitro was accomplished using a specially created N- and C-terminal-tagged Luman adenoviral vector. Small interfering RNA used to reduce Luman expression either neuronally or just axonally significantly impaired the ability of 24-h injury-conditioned sensory neurons to extend the regeneration-associated elongating form of axon growth but had no impact on axon outgrowth in naïve neurons. Collectively, these findings link injury-associated axonal ER responses proximal to the site of injury to the intrinsic regenerative growth capacity of adult sensory neurons.

Posttraumatic abducens to oculomotor nerve misdirection

Paradoxical patterns of extraocular muscle, eyelid, or pupillary movements can occur following injury between divisions of the oculomotor nerve, trigeminal and abducens nerves, and trigeminal and oculomotor nerves. We report three cases of unusual ocular motility and eyelid movements that are a result of aberrant connections between the abducens and oculomotor nerves. Three patients with unusual eye movement abnormalities after trauma were studied. A complete ophthalmic examination plus neuroradiologic evaluation were performed. Each patient manifested an aberrant connection between the 6th and 3rd cranial nerves resulting in third nerve function during sixth nerve stimulation. Two patients demonstrated complete third nerve palsies except for adduction on attempted abduction. The third showed improved bilateral ptosis on abduction. The neuroanatomical abnormalities involve intraorbital structures in one patient and central nervous system pathways in the others. Explanations such as retrograde regeneration, ephaptic transmission, or denervation supersensitivity do not appear to explain these unusual eye movements. The most likely mechanism involves some form of peripheral neuronal misdirection. These rare sixth to third nerve misdirection cases add support to the "neuronal misdirection hypothesis" of aberrant eye movements after trauma.

Retrograde impulse activity and horseradish peroxidase tracig of nerve fibers entering neuroma studied in vitro

Neuroma formation was induced in rat sciatic nerve by tight ligature. At various times after placement of the ligature, the nerves were excised, desheathed, split longitudinally proximal to the neuroma, and studied in vitro in a nerve chamber. Stimulation of one of the arbitrarily formed proximal branches was found to generate impulse activity in the other branch. Since similar branch to branch activation did not occur in control preparations, it appeared that some form of axon to axon interaction occurred within the neuroma, or alternatively that retrograde regeneration allowed continuity of nerve fibers in proximal divisions of the nerve trunk. Attempts at morphological demonstration of the continuity alternative were made by applying horseradish peroxidase to cut fibers of one proximal division. Although labeled axons did turn retrogradely within the neuroma, they were not found to enter the other nerve division.