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PubMed2000

In goldfish the discriminative ability for odours persists after reduction of the olfactory epithelium, and rapidly returns after olfactory nerve axotomy and crossing bulbs.

Goldfish are ideal vertebrates for the study of regeneration within the peripheral and the central olfactory system. The present behavioural investigations studied the effects of bilateral lesions on the animals' ability to qualitatively discriminate two amino acids (10(-6) M) and their performance in two more difficult tasks: (i) rewarded amino acid applied in a lower concentration, and (ii) rewarded stimulus contaminated. A 50 and 85% reduction of the olfactory epithelium resulted in no recordable behavioural deficit. After axotomy of olfactory nerves and lateral olfactory tractotomy, fishes were anosmic for seven to ten days. Following replacement of sensory cells in the epithelium, and after regeneration of olfactory tract fibres a full functional recovery i.e. a highly specific regeneration, was recorded. After three surgical modifications of the olfactory bulbs' position, (i) crossing olfactory tracts and bulbs, (ii) crossing tracts and turning bulbs, and (iii) turning bulbs upside down, a full functional recovery was recorded for amino-acid discrimination in a similar concentration. A permanent, and similar slight deficit was, however, found during application of different concentrations, and of contaminated stimuli when medial lateral halves of the bulb were in 'incorrect' position (i) and (ii), or olfactory bulbs were positioned in the vicinity of the contralateral epithelium (i) and (ii).

Animals↗
PubMed2005

Adult motor neurons show increased susceptibility to axotomy-induced death in mice lacking clusterin.

Clusterin is a highly conserved, amphiphatic glycoprotein present in most tissues. It has been shown to be involved in the regulation of lipid transportation, clearance of cellular debris from the extracellular space and intracellular signal transduction. Clusterin is markedly up-regulated after neural injury but the functional significance of this response is unclear. Here, we show that clusterin up-regulation is substantially greater in hypoglossal motor neurons after hypoglossal nerve avulsion compared with nerve transection. Quantitative analyses of motor neuron numbers after the same lesions in clusterin(-/-) and clusterin(+/+) mice showed significantly larger numbers of surviving motor neurons in clusterin(+/+) mice. These results suggest that clusterin has a neuroprotective role after axotomy.

Animals↗
PubMed1998

Rescue of alpha-SNS sodium channel expression in small dorsal root ganglion neurons after axotomy by nerve growth factor in vivo.

Small (18-25 microm diam) dorsal root ganglion (DRG) neurons are known to express high levels of tetrodotoxin-resistant (TTX-R) sodium current and the mRNA for the alpha-SNS sodium channel, which encodes a TTX-R channel when expressed in oocytes. These neurons also preferentially express the high affinity receptor for nerve growth factor (NGF), TrkA. Levels of TTX-R sodium current and of alpha-SNS mRNA are reduced in these cells after axotomy. To determine whether NGF participates in the regulation of TTX-R current and alpha-SNS mRNA in small DRG neurons in vivo, we axotomized small lumbar DRG neurons by sciatic nerve transection and administered NGF or Ringer solution to the proximal nerve stump using osmotic pumps. Ten to 12 days after pump implant, whole cell patch-clamp recording demonstrated that TTX-R current density was decreased in Ringer-treated axotomized neurons (154 +/- 45 pA/pF; mean +/- SE) compared with nonaxotomized control neurons (865 +/- 123 pA/pF) and was restored partially toward control levels in NGF-treated axotomized neurons (465 +/- 78 pA/pF). The V1/2 for steady-state activation and inactivation of TTX-R currents were similar in control, Ringer- and NGF-treated axotomized neurons. Reverse transcription polymerase chain reaction revealed an upregulation of alpha-SNS mRNA levels in NGF-treated compared with Ringer-treated axotomized DRG. In situ hybridization showed that alpha-SNS mRNA levels were decreased significantly in small Ringer-treated axotomized DRG neurons in vivo and also in small DRG neurons that were dissociated and maintained in vitro, so as to correspond to the patch-clamp conditions. NGF-treated axotomized neurons had a significant increase in alpha-SNS mRNA expression, compared with Ringer-treated axotomized cells. These results show that the administration of exogenous NGF in vivo, to the proximal nerve stump of the transected sciatic nerve, results in an upregulation of TTX-R sodium current and of alpha-SNS mRNA levels in small DRG neurons. Retrogradely transported NGF thus appears to participate in the control of excitability in these cells via actions that include the regulation of sodium channel gene expression in vivo.

Animals↗
PubMed2002

Protective effect of interleukin-3 and erythropoietin on motor neuron death after neonatal axotomy.

Several members of hematopoietic factors are known to have neuroprotective effects against axotomized motor neuron death. We carried out a study to determine whether interleukin-3 (IL-3) and erythropoietin (EPO) rescue spinal motor neuron death following axotomy. Unilateral sciatic nerve was transected in neonatal rats. Different doses of IL-3, EPO, or vehicle were administered daily for two weeks by intraperitoneal injection. After treatment, the number of spinal motor neurons was determined at the level of L4 segment In comparison with vehicle, both IL-3 (10 microg kg(-1)) and EPO (5.0 mg kg(-1)) significantly prevented the loss of motor neurons. Protective potentials is the same between them. These results suggest that IL-3 and EPO play a role for motor neuron survival in vivo and suggest the potential use of these hematopoietic factors in treating diseases that involve degeneration and death of motor neurons, such as motor neuropathy and amyotrophic lateral sclerosis.

Animals↗
PubMed2004

A neuronal isoform of protein kinase G couples mitogen-activated protein kinase nuclear import to axotomy-induced long-term hyperexcitability in Aplysia sensory neurons.

The induction of a long-term hyperexcitability (LTH) in vertebrate nociceptive sensory neurons (SNs) after nerve injury is an important contributor to neuropathic pain in humans, but the signaling cascades that induce this LTH have not been identified. In particular, it is not known how injuring an axon far from the cell soma elicits changes in gene expression in the nucleus that underlie LTH. The nociceptive SNs of Aplysia (ap) develop an LTH with electrophysiological properties after axotomy similar to those of mammalian neurons and are an experimentally useful model to examine these issues. We cloned an Aplysia PKG (cGMP-dependent protein kinase; protein kinase G) that is homologous to vertebrate type-I PKGs and found that apPKG is activated at the site of injury in the axon after peripheral nerve crush. The active apPKG is subsequently retrogradely transported to the somata of the SNs, but apPKG activity does not appear in other neurons whose axons are injured. In the soma, apPKG phosphorylates apMAPK (Aplysia mitogen-activated protein kinase), resulting in its entry into the nucleus. Surprisingly, studies using recombinant proteins in vivo and in vitro indicate that apPKG directly phosphorylates the threonine moiety in the T-E-Y activation site of apMAPK when the -Y- site contains a phosphate. We used inhibitors of nitric oxide synthase, soluble guanyl cyclase, or PKG after nerve injury, and found that each prevented the appearance of the LTH. Moreover, blocking apPKG activation prevented the nuclear import of apMAPK. Consequently, the nitric oxide-PKG-MAPK pathway is a potential target for treatment of neuropathic pain.

Active Transport, Cell Nucleus↗
PubMed2006

Stimulation of nicotinamide adenine dinucleotide biosynthetic pathways delays axonal degeneration after axotomy.

Axonal degeneration occurs in many neurodegenerative diseases and after traumatic injury and is a self-destructive program independent from programmed cell death. Previous studies demonstrated that overexpression of nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1) or exogenous application of nicotinamide adenine dinucleotide (NAD) can protect axons of cultured dorsal root ganglion (DRG) neurons from degeneration caused by mechanical or neurotoxic injury. In mammalian cells, NAD can be synthesized from multiple precursors, including tryptophan, nicotinic acid, nicotinamide, and nicotinamide riboside (NmR), via multiple enzymatic steps. To determine whether other components of these NAD biosynthetic pathways are capable of delaying axonal degeneration, we overexpressed each of the enzymes involved in each pathway and/or exogenously administered their respective substrates in DRG cultures and assessed their capacity to protect axons after axotomy. Among the enzymes tested, Nmnat1 had the strongest protective effects, whereas nicotinamide phosphoribosyl transferase and nicotinic acid phosphoribosyl transferase showed moderate protective activity in the presence of their substrates. Strong axonal protection was also provided by Nmnat3, which is predominantly located in mitochondria, and an Nmnat1 mutant localized to the cytoplasm, indicating that the subcellular location of NAD production is not crucial for protective activity. In addition, we showed that exogenous application of the NAD precursors that are the substrates of these enzymes, including nicotinic acid mononucleotide, nicotinamide mononucleotide, and NmR, can also delay axonal degeneration. These results indicate that stimulation of NAD biosynthetic pathways via a variety of interventions may be useful in preventing or delaying axonal degeneration.

Animals↗
PubMed2002

TrkB gene transfer protects retinal ganglion cells from axotomy-induced death in vivo.

Injury-induced downregulation of neurotrophin receptors may limit the response of neurons to trophic factors, compromising their ability to survive. We tested this hypothesis in a model of CNS injury: retinal ganglion cell (RGC) death after transection of the adult rat optic nerve. TrkB mRNA rapidly decreased in axotomized RGCs to approximately 50% of the level in intact retinas. TrkB gene transfer into RGCs combined with exogenous BDNF administration markedly increased neuronal survival: 76% of RGCs remained alive at 2 weeks after axotomy, a time when >90% of these neurons are lost without treatment. Activation of mitogen-activated protein kinase, but not phosphatidylinositol-3 kinase, was required for TrkB-induced survival. These data provide proof-of-principle that enhancing the capacity of injured neurons to respond to trophic factors can be an effective neuroprotective strategy in the adult CNS.

Animals↗
PubMed1999

Differential expression of the mRNA for the vanilloid receptor subtype 1 in cells of the adult rat dorsal root and nodose ganglia and its downregulation by axotomy.

Sensitivity to the pungent vanilloid, capsaicin, defines a subpopulation of primary sensory neurons that are mainly polymodal nociceptors. The recently cloned vanilloid receptor subtype 1 (VR1) is activated by capsaicin and noxious heat. Using combined in situ hybridization and histochemical methods, we have characterized in sensory ganglia the expression of VR1 mRNA. We show that this receptor is almost exclusively expressed by neurofilament-negative small- and medium-sized dorsal root ganglion cells. Within this population, VR1 mRNA is detected at widely varying levels in both the NGF receptor (trkA)-positive, peptide-producing cells that elicit neurogenic inflammation and the functionally less characterized glial cell line-derived neurotrophic factor-responsive cells that bind lectin Griffonia simplicifolia isolectin B4 (IB4). Cells without detectable levels of VR1 mRNA are found in both classes. A subpopulation of the IB4-binding cells that produce somatostatin has relatively low levels of VR1 mRNA. A previously uncharacterized population of very small cells that express the receptor tyrosine kinase (RET) and that do not label for trkA or IB4-binding has the highest relative levels of VR1 mRNA. The majority of small visceral sensory neurons of the nodose ganglion also express VR1 mRNA, in conjunction with the BDNF receptor trkB but not trkA. Axotomy results in the downregulation of VR1 mRNA in dorsal root ganglion cells. Our data emphasize the heterogeneity of VR1 mRNA expression by subclasses of small sensory neurons, and this may result in their differential sensitivity to chemical and noxious heat stimuli. Our results also indicate that peripherally derived trophic factors may regulate levels of VR1 mRNA.

Animals↗
PubMed2002

Traumatically induced axotomy adjacent to the soma does not result in acute neuronal death.

Traumatic axonal injury (TAI), a consequence of traumatic brain injury (TBI), results from progressive pathologic processes initiated at the time of injury. Studies attempting to characterize the pathology associated with TAI have not succeeded in following damaged and/or disconnected axonal segments back to their individual neuronal somata to determine their fate. To address this issue, 71 adult male Sprague Dawley rats were subjected to moderate central fluid percussion injury and killed between 30 min and 7 d after injury. Antibodies to the C terminus of beta-amyloid precursor protein (APP) identified TAI in continuity with individual neuronal somata in the mediodorsal neocortex, the hilus of the dentate gyrus, and the dorsolateral thalamus. These somata were followed with immunocytochemical markers of neuronal injury targeting phosphorylated 200 kDa neurofilaments (RMO-24), altered protein translation (phosphorylated eukaryotic translation initiation factor 2 alpha), and cell death [terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)], with parallel electron microscopic (EM) assessment. Despite the finding of TAI within 20-50 micrometer of the soma, no evidence of cell death, long associated with proximal axotomy, was seen via TUNEL or routine light microscopy/electron microscopy. Rather, there was rapid onset (<6 hr after injury) subcellular change associated with impaired protein synthesis identified by EM, immunocytochemical, and Western blot analyses. When followed 7 d after injury, these abnormalities did not reveal dramatic progression. Rather, some somata showed evidence of potential reorganization and repair. This study demonstrates a novel somatic response to TAI in the perisomatic domain and also provides insight into the multifaceted pathology associated with TBI.

Amyloid beta-Protein Precursor↗
PubMed2003

Fas/tumor necrosis factor receptor death signaling is required for axotomy-induced death of motoneurons in vivo.

Activation of the Fas death receptor leads to the death of motoneurons in culture. To investigate the role of Fas in programmed cell death and pathological situations, we used several mutant mice deficient for Fas signaling and made a novel transgenic FADD-DN (FAS-associated death domain-dominant-negative) strain. In vitro, motoneurons from all of these mice were found to be resistant to Fas activation and to show a delay in trophic deprivation-induced death. During normal development in vivo, no changes in motoneuron survival were observed. However, the number of surviving motoneurons was twofold higher in animals deficient for Fas signaling after facial nerve transection in neonatal mice. These results reveal a novel role for Fas as a trigger of axotomy-induced death and suggest that the Fas pathway may be activated in pathological degeneration of motoneurons.

Actins↗
PubMed2003

Downregulation of voltage-gated potassium channel alpha gene expression by axotomy and neurotrophins in rat dorsal root ganglia.

Injury to peripheral nerves causes a neuropathic pain which is difficult to relieve, but the underlying mechanism remains largely unknown. In previous studies we reported that voltage-gated potassium (Kv) channel alpha genes are downregulated in the dorsal root ganglia (DRG) following chronic constriction of the sciatic nerve [Kim et al. (2002)], suggesting a relationship between electrical abnormalities of the injured neurons and Kv gene expression. Here, we examined expression of the Kv 1.2, 1.4, and 4.2 genes in the DRG following transection of the sciatic nerve, and investigated the effect of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) on expression of those mRNAs, using the reverse transcription-polymerase chain reaction. Expression of these mRNAs was reduced by axotomy and by exposure to BDNF, and NT-3 treatment. However no significant change was detected following NGF treatment. Our findings suggest that downregulation of Kv channel gene expression in DRG neurons by neurotrophins may play an important role in long-term changes of neuronal excitability following nerve injury.

Animals↗
PubMed1998

Short-term afferent axotomy increases both strength and depression at Ia-motoneuron synapses in Rat.

Synaptic efficacy at the rat Ia-motoneuron synapse has been reported to increase in vivo, within 3 d of sectioning a single muscle nerve (). We provide an indirect test of the hypothesis that this increase is caused by altered probability of transmitter release of axotomized afferents. Experiments consisted of in vivo recording of maximal composite group I EPSPs evoked in intact rat medial gastrocnemius (MG) motoneurons by stimulation of the lateral gastrocnemius-soleus nerve (LG-S). We compared the maximal LG-S EPSP amplitude and the response to high-frequency stimulation (modulation) recorded in untreated rats, with the same measures recorded in rats that had the LG-S nerve axotomized 3 d before data collection. In confirmation of previous work, the mean amplitude of LG-S EPSPs evoked by stimulation of axotomized afferents was significantly larger than that measured in untreated rats (3.9 +/- 0. 34 and 2.3 +/- 0.19 mV, respectively). The increase in EPSP amplitude was accompanied by significantly greater negative modulation (depression) of EPSP amplitude during high-frequency stimulation (-39 +/- 4% and -53 +/- 4%, untreated and treated, respectively). Modulation would not be expected to change if the increase in EPSP amplitude was attributable solely to a greater number of afferent connections (). Therefore, the present results are consistent with the hypothesis that the initial axotomy-induced increase in synaptic efficacy occurs because of an increase in the probability of transmitter release. Furthermore, these results suggest that the probability of transmitter release at this synapse is regulated by either afferent activity and/or trophic communication with the target muscle.

Animals↗
PubMed1998

Peripheral axotomy induces long-term c-Jun amino-terminal kinase-1 activation and activator protein-1 binding activity by c-Jun and junD in adult rat dorsal root ganglia In vivo.

One of the earliest documented molecular events after sciatic nerve injury in adult rats is the rapid, long-term upregulation of the immediate early gene transcription factor c-Jun mRNA and protein in lumbar dorsal root ganglion (DRG) neurons, suggesting that c-Jun may regulate genes that are important both in the early post-injury period and during later peripheral axonal regeneration. However, neither the mechanism through which c-Jun protein is increased nor the level of its post-injury transcriptional activity in axotomized DRGs has been characterized. To determine whether transcriptional activation of c-Jun occurs in response to nerve injury in vivo and is associated with axonal regeneration, we have assayed axotomized adult rat DRGs for evidence of jun kinase activation, c-Jun phosphorylation, and activator protein-1 (AP-1) binding. We report that sciatic nerve transection resulted in chronic activation of c-Jun amino-terminal kinase-1 (JNK) in L4/L5 DRGs concomitant with c-Jun amino-terminal phosphorylation in neurons, and lasting AP-1 binding activity, with both c-Jun and JunD participating in DNA binding complexes. The timing of JNK activation was dependent on the distance of the axotomy site from the DRGs, suggesting the requirement for a retrograde transport-mediated signal. AP-1 binding and c-Jun protein returned to basal levels in DRGs as peripheral regeneration was completed but remained elevated in the case of chronic sprouting, indicating that c-Jun may regulate target genes that are involved in axonal outgrowth.

Animals↗
PubMed1997

Brain-derived neurotrophic factor spares choline acetyltransferase mRNA following axotomy of motor neurons in vivo.

Choline acetyltransferase (ChAT) is a functional and specific marker gene for neurons such as primary motor neurons that synthesize and release acetylcholine as a neurotransmitter. In adult mammals, transection of the peripheral nerve results in a loss of immunoreactivity for ChAT in the injured motor neurons without affecting their cell number. Using a quantitative RNase protection assay, we have investigated dynamic changes in ChAT mRNA levels following axotomy of motor neurons in the brainstem of adult rats. One week after transection of the left hypoglossal nerve, levels of ChAT mRNA in the ipsilateral side of the hypoglossal motor nucleus decreased dramatically to around 10% when compared to the uninjured contralateral side. When cut axons were chronically exposed to brain-derived neurotrophic factor (BDNF) for 1 week, ChAT mRNA levels were maintained at 63% of control levels. Thus, BDNF can abrogate the injury-induced loss of ChAT mRNA in mature motor neurons in vivo. In contrast, neither neurotrophin 4/5 nor nerve growth factor could prevent the decrease in message. This effect of BDNF on ChAT mRNA levels following peripheral injury to motor neurons demonstrates the existence of regulatory pathways responsive to neurotrophic factors that can "rescue" or "protect" cholinergic gene expression.

Animals↗
PubMed1984

Astrocytic membrane morphology: differences between mammalian and amphibian astrocytes after axotomy.

Previous studies have shown that astrocytes in some nonmammalian species provide a favorable environment for axonal elongation, whereas mammalian astrocytes are thought to inhibit fiber outgrowth. The present study was performed to determine whether any plasma membrane differences exist between these glial elements which could account for their contrasting effects upon axonal outgrowth. Astrocytic scars were formed in optic nerves of rats, newts, and frogs by enucleation. Subsequently, the astrocytic membranes were examined with the freeze-fracture technique. Orthogonal arrays of small intramembranous particles (IMPs) are a prominent component of the plasma membranes of normal mammalian astrocytes; these arrays are most numerous in astrocytic membranes that form an interface between the CNS and nonneural tissue. Astrocytic membranes within the normal CNS parenchyma, however, possess much lower densities of arrays. Following axotomy and Wallerian degeneration, the density of arrays increased threefold within the parenchyma of the optic nerve, while remaining constant at the glia limitans. In striking contrast, only a few aggregates of IMPs that resembled orthogonal arrays could be found in normal and reactive astrocytes of amphibians, although the cytology of these glial cells and density of the scars are otherwise similar to those of their mammalian counterparts. These findings suggest (1) that a proliferation of orthogonal arrays in astrocytic plasma membranes is a prominent feature of gliosis in the mammalian CNS and (2) that differences in the composition of reactive mammalian and amphibian astrocytic membranes may account for variations in axonal-glial interactions within the injured CNS.

Aging↗
PubMed1986

Electrophysiological and morphological correlates of axotomy-induced deafferentation of the goldfish Mauthner cell.

Axotomy-induced changes in afferent synapses to the goldfish Mauthner cell have been analyzed with intracellular recordings and with electron microscopy. The studies encompassed 7-208 days after cervical spinal cord transection. The physiological findings suggest a persistent and specific reduction in excitatory chemical inputs to the soma and proximal lateral dendrite, with no changes in somatic inhibition or in the electrotonic and chemical inputs to the more distal regions of the lateral dendrite. Corroborative morphological evidence includes swelling of the M-cell soma, as indicated by a 35% increase in the length of its minor diameter, an increased spacing and a quantitatively lower density of terminals on the soma, and the appearance of astrocytic processes partially or completely engulfing the terminals in that region. Similar changes were observed on the inferior dendrites projecting from the ventral surface of the soma, although these dendrites do not exhibit the chromatolytic changes observed at the soma. In contrast, there are no noticeable changes in either the synaptic investment of the lateral dendrite or its ultrastructure. Quantitative and qualitative data support the conclusion that there is a restricted and specific reduction in the proximal excitatory inputs to the M-cell. The evidence also suggests that electrotonic junctions between afferents and the M-cell remain intact, functionally and structurally.

Afferent Pathways↗
PubMed1988

Neuronal surface changes in the dorsal vagal motor nucleus of the guinea pig in response to axotomy.

Ultrastructural changes occurring in the dorsal motor nucleus of the vagus of the guinea pig after nerve transection were investigated. Two neuronal populations could be distinguished. Large neurons corresponding to the vagal motoneurons showed chromatolysis. They were found to develop complex changes in cell surface, which appeared either as a folding up and formation of flaplike processes or as invagination of adjacent neuronal or glial elements. Large processes often covered part of the plasmalemma and formed stacks of several neuronal lamellae. Smaller processes were mostly seen to extend into the neuropil, where they intermingled and adopted a budlike shape. These changes occurred in the cell somata within the first week after axotomy. The dendrites were affected after a short delay. The changes persisted for several months in most of the neurons, including the ones that showed signs of recovery from chromatolysis. The newly formed cellular extensions had a growth-cone-like internal structure, containing numerous smooth-surfaced vesicles or cisternae, a feltwork of filamentous material, dense-cored vesicles, and occasionally free polyribosomes. These surface changes did not occur in the second neuronal cell type of this nucleus, which had a smaller perikaryon characterized by a scanty cytoplasm. These cells did not show a retrograde degeneration and thus are probably interneurons. Acetylcholinesterase was used as a cytochemical marker of neuronal membranes. Surprisingly, the vagal motoneurons did not show a loss of enzymatic activity after nerve transection. Rather, a redistribution seemed to occur with intensified staining of the plasmalemma. The newly formed processes were consistently found to be acetylcholinesterase positive. It is suggested that the morphological changes observed correspond to an as-yet-unobserved growth process in the adult central nervous system, which involves perikarya and dendrites of regenerating guinea pig vagal motoneurons.

Acetylcholinesterase↗
PubMed1989

Fetal brain grafts rescue adult retinal ganglion cells from axotomy-induced cell death.

After intraorbital transection of the optic nerve of adult rats, 90% of the retinal ganglion cells die within 30 days. Since fetal brain extracts and cocultured fetal target regions support the survival of retinal ganglion cells in vitro (Nurcombe and Bennett: Exp. Brain Res. 44: 249-258, '81; McCaffery et al.: Exp. Brain Res. 48: 377-386, '82; Armson and Bennett: Neurosci. Lett. 38: 181-186, '83) we investigated whether cell death in the adult retina could be prevented by transplanting fetal (E16) thalamus and tectum to the proximal stump of the optic nerve of adult rats that was completely transected 2-3 mm behind the optic disc. Unoperated eyes contained 119,973 (+/- 939, SEM) retinal ganglion cells, estimated from axon counts of the intact optic nerve. Of these, 11,601 (+/- 1,857) remained in control operated eyes at 30 days postoperation while in the eyes of grafted rats, 35,086 (+/- 2,278) retinal ganglion cells were counted. Thus, 23,485 (= 22% of those normally dying after transection of the optic nerve) ganglion cells were rescued by the fetal grafts from cell death normally following axotomy. These results indicate that fetal target regions of retinal ganglion cells contain and/or produce neurotrophic molecules that promote the survival of adult axotomized retinal ganglion cells.

Animals↗