One eyelid has been sutured in each of three seven-day old kittens.Three months later the brains were fixed and stained by the Nissl method. In the contralateral lateral geniculate nucleus the cells of the deprived lamina A were smaller, more closely packed and paler staining than those i n the normally innervated, ipsilateral lamina A. However, these changes were seen in the medial parts of the contralateral lamina A only. The lateral parts, which extend beyond the border of lamina A1 and which project to the monocular parts of the visual cortex showed no change.These results show that some geniculate cells are not affected by deprivation. The observations are consistent with the view that during normal development geniculate cell axons from adjacent laminae compete with each other for synaptic surfaces upon binocular cortical neurons: that unilateral lid suture upsets the balance of this competition and that the reduced perikaryal growth in the lateral geniculate nucleus is secondary to the unbalanced axonal development, which occurs in the binocular portions of the geniculocortical projection but which cannot occur in the monocular portions, where there is no competition.

BackgroundCentral nervous system axons lack a robust regenerative response following spinal cord injury (SCI) and regeneration is usually abortive. Supraspinal pathways, which are the most commonly studied for their regenerative potential, demonstrate a limited regenerative ability. On the other hand, propriospinal (PS) neurons, with axons intrinsic to the spinal cord, have shown a greater regenerative response than their supraspinal counterparts, but remain relatively understudied in regards to spinal cord injury.ResultsUtilizing laser microdissection, gene-microarray, qRT-PCR, and immunohistochemistry, we focused on the intrinsic post-axotomy response of specifically labelled thoracic propriospinal neurons at periods from 3-days to 1-month following T9 spinal cord injury. We found a strong and early (3-days post injury, p.i) upregulation in the expression of genes involved in the immune/inflammatory response that returned towards normal by 1-week p.i. In addition, several regeneration associated and cell survival/neuroprotective genes were significantly up-regulated at the earliest p.i. period studied. Significant upregulation of several growth factor receptor genes (GFRa1, Ret, Lifr) also occurred only during the initial period examined. The expression of a number of pro-apoptotic genes up-regulated at 3-days p.i. suggest that changes in gene expression after this period may have resulted from analyzing surviving TPS neurons after the cell death of the remainder of the axotomized TPS neuronal population.ConclusionsTaken collectively these data demonstrate that thoracic propriospinal (TPS) neurons mount a very dynamic response following low thoracic axotomy that includes a strong regenerative response, but also results in the cell death of many axotomized TPS neurons in the first week after spinal cord injury. These data also suggest that the immune/inflammatory response may have an important role in mediating the early strong regenerative response, as well as the apoptotic response, since expression of all of three classes of gene are up-regulated only during the initial period examined, 3-days post-SCI. The up-regulation in the expression of genes for several growth factor receptors during the first week post-SCI also suggest that administration of these factors may protect TPS neurons from cell death and maintain a regenerative response, but only if given during the early period after injury.

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The glial scar formed at the site of traumatic spinal cord injury (SCI) has been classically hypothesized to be a potent physical and biochemical barrier to nerve regeneration. One longstanding hypothesis is that the scar acts as a physical barrier due to its increased stiffness in comparison to uninjured spinal cord tissue. However, the information regarding the mechanical properties of the glial scar in the current literature is mostly anecdotal and not well quantified. We monitored the mechanical relaxation behavior of injured rat spinal cord tissue at the site of mid-thoracic spinal hemisection 2 weeks and 8 weeks post-injury using a microindentation test method. Elastic moduli were calculated and a modified standard linear model (mSLM) was fit to the data to estimate the relaxation time constant and viscosity. The SLM was modified to account for a spectrum of relaxation times, a phenomenon common to biological tissues, by incorporating a stretched exponential term. Injured tissue exhibited significantly lower stiffness and elastic modulus in comparison to uninjured control tissue, and the results from the model parameters indicated that the relaxation time constant and viscosity of injured tissue were significantly higher than controls. This study presents direct micromechanical measurements of injured spinal cord tissue post-injury. The results of this study show that the injured spinal tissue displays complex viscoelastic behavior, likely indicating changes in tissue permeability and diffusivity.

The propriospinal system is important in mediating reflex control and in coordination during locomotion. Propriospinal neurons (PNs) present varied patterns of projections with ascending and/or descending fibers. Following spinal cord contusion injury (SCI) in the rat, certain supraspinal pathways, such as the corticospinal tract, appear to be completely abolished, whereas others, such as the rubrospinal and vestibuospinal tracts, are only partially damaged. The amount of damage to propriospinal axons following different severities of SCI is not fully known. In the present study retrograde and anterograde tracing techniques were used to assess the projection patterns of propriospinal neurons in order to determine how this system is affected following SCI. Our findings reveal that PNs have differential vulnerabilities to SCI. While short thoracic propriospinal axons are severely damaged after injury, 5-7% of long descending propriospinal tract (LDPT) projections survive following 50 and 12.5-mm weight drop contusion lesions, respectively, albeit with a reduced intensity of retrograde label. Even though the axons of short thoracic propriospinal cells are damaged, their cell bodies of origin remain intact 2 weeks after injury, indicating that they have not undergone postaxotomy retrograde cell death at this time point. Thus, short PNs may constitute a very attractive population of cells to study regenerative approaches, whereas LDPT neurons with spared axons could be targeted with therapeutic interventions, seeking to enhance recovery of function following incomplete lesions to the spinal cord.

Olfactory ensheathing cells (OECs) and Schwann cells (SCs) obtained from adult transgenic rats expressing alkaline phosphatase (AP) were studied following implantation into intact spinal cord and after dorsal column crush (DCC) injury, either within the lesion or near the lesion borders. We observed no evidence of migration of AP OECs or AP SCs after lesion site injections, with most cells remaining in or nearby the injection/lesion site. Acute injection of either cell type outside of the lesion site resulted in the presence of cells in the lesion even two hours after injection. However, after a 2-week delay between DCC injury and cell injection, only OECs injected 2.5-mm outside of a DCC lesion entered the lesion, while SCs did not pass a region of increased astroglial immunoreactivity. GFAP-immunoreactivity also revealed differences in the astroglial scar at the lesion border with openings apparent in this region only in the OEC group. SCs induced greater ingrowth of CGRP-positive axons within the lesion, two weeks post-injury. Equivalent numbers of GAP-43-positive axons grew within the lesion after SC or OEC implantation. These findings show that, although there is no active migration for either cell type, both OECs and SCs are able to support axonal regrowth and/or sprouting into the lesion. The openings in the astroglial boundary at the lesion site may give OECs a potential advantage over SCs in promoting axonal growth through the astroglial scar.

BackgroundPropriospinal neurons, with axonal projections intrinsic to the spinal cord, have shown a greater regenerative response than supraspinal neurons after axotomy due to spinal cord injury (SCI). Our previous work focused on the response of axotomized short thoracic propriospinal (TPS) neurons following a low thoracic SCI (T9 spinal transection or moderate spinal contusion injury) in the rat. The present investigation analyzes the intrinsic response of cervical propriospinal neurons having long descending axons which project into the lumbosacral enlargement, long descending propriospinal tract (LDPT) axons. These neurons also were axotomized by T9 spinal injury in the same animals used in our previous study.ResultsUtilizing laser microdissection (LMD), qRT-PCR, and immunohistochemistry, we studied LDPT neurons (located in the C5-C6 spinal segments) between 3-days, and 1-month following a low thoracic (T9) spinal cord injury. We examined the response of 89 genes related to growth factors, cell surface receptors, apoptosis, axonal regeneration, and neuroprotection/cell survival. We found a strong and significant down-regulation of ~25% of the genes analyzed early after injury (3-days post-injury) with a sustained down-regulation in most instances. In the few genes that were up-regulated (Actb, Atf3, Frs2, Hspb1, Nrap, Stat1) post-axotomy, the expression for all but one was down-regulated by 2-weeks post-injury. We also compared the uninjured TPS control neurons to the uninjured LDPT neurons used in this experiment for phenotypic differences between these two subpopulations of propriospinal neurons. We found significant differences in expression in 37 of the 84 genes examined between these two subpopulations of propriospinal neurons with LDPT neurons exhibiting a significantly higher base line expression for all but 3 of these genes compared to TPS neurons.ConclusionsTaken collectively these data indicate a broad overall down-regulation in the genes examined, including genes for neurotrophic/growth factor receptors as well as for several growth factors. There was a lack of a significant regenerative response, with the exception of an up-regulation of Atf3 and early up-regulation of Hspb1 (Hsp27), both involved in cell stress/neuroprotection as well as axonal regeneration. There was no indication of a cell death response over the first month post-injury. In addition, there appear to be significant phenotypic differences between uninjured TPS and LDPT neurons, which may partly account for the differences observed in their post-axotomy responses. The findings in this current study stand in stark contrast to the findings from our previous work on TPS neurons. This suggests that different approaches will be needed to enhance the capacity for each population of propriospinal neuron to survive and undergo successful axonal regeneration after SCI.