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PubMed2005

Evoked potentials in severe brain injury.

Three-modality evoked potentials (EPs) have been used for several years in association with the electroencephalogram (EEG) as a diagnostic and prognostic tool in acute traumatic or nontraumatic coma. In 1993 we proposed to combine these in two indices: the index of global cortical function (IGCF) and the index of brain-stem conduction (IBSC). Four EP patterns based on both indices emerge at the acute stage of severe head trauma. These are easily explainable by pathophysiology. Pattern 1 corresponds to alterations in the index of global cortical function without changes in the index of brain-stem conduction. Its prognosis is good (80 to 90% of these patients recover). Pattern 2 is characterized by alterations of somatosensory EPs that are suggestive of midbrain dysfunction. The prognosis depends both on the reversibility of the midbrain dysfunction and on the extent of associated diffuse axonal lesions, whose evaluation requires MRI. Patients who recovered from Pattern 2 sometimes did so after a long interval during which they remained vegetative. Pattern 3 is characterized by alterations of brain-stem auditory EPs that are suggestive of pontine involvement. It usually follows uncontrolled intracranial hypertension and corresponds to evolving transtentorial herniation. All patients with that transient pattern eventually died. Pattern 4 is categorized by the disappearance of all activities of intracranial origin, contrasting with the preservation of all activities of retinal, spinal-cord, and peripheral-nerve origin. This pattern corresponds to brain death. In our experience, three-modality EPs are currently the best bedside brain-death confirmatory tool.

Brain↗
PubMed1990

Radiation-induced ocular injury in the dog: a histological study.

Radiation-induced ocular injury secondary to treatment of nasal cancer occurs in humans and animals. Dogs with nasal carcinomas were randomized to receive 36 to 67.5 Gy in fractionated doses given in 4 weeks using a 6 MV linear accelerator. Ophthalmic examinations were performed according to a predetermined protocol and eyes were removed for histologic examination when dogs were euthanatized. The eye in the radiation field exhibited greater injury than the contralateral eye with nasal areas of the globe having more severe lesions than temporal areas. Lesions occurred in all dogs and at all doses. At 1 month or less postirradiation treatment, all dogs had blepharitis, keratoconjunctivitis and corneal epithelial atrophy. Surface lesions persisted in all eyes, becoming less severe and more chronic with time. At 3-6 months postirradiation treatment, degenerative angiopathy of retinal vessels appeared with multifocal retinal hemorrhage and mild diffuse retinal degeneration which affected outer layers first and progressed inwardly with time. At 6 months postirradiation treatment, there were cataracts, fibrosis of retinal vessel walls with loss of vascular smooth muscle, retinal hemorrhage, and mild to moderate retinal degeneration. At 1 year postirradiation treatment, retinal vessels remained sclerotic, retinal hemorrhage was less frequent, and there was moderate retinal degeneration with swelling and loss of ganglion cells. By 2 years or more postirradiation treatment, optic nerve axonal degeneration secondary to retinal changes had appeared. Tapetal and choroidal atrophy were inconsistently seen. Thus, ocular lesions at the doses received developed along a relatively predictable time course and recovery was not seen. Structures of the canine eye appear sufficiently sensitive that even relatively low total doses given in small doses per fraction cause significant long-term injury.

Animals↗
PubMed2000

[A case of mortor neuron syndrome with onset 9 months after electrical injury].

A 72-year-old man noticed progressive weakness of both upper limbs, more severe on the left side, 9 months after an electric shock of a 20,000 V alternating current. He had diffuse scars of superficial burns with skin graft in four limbs, more on the right side. A neurological examination revealed diffuse muscle atrophy, weakness and fasciculation in both upper limbs, predominantly on the left side, hyper-reflexia in four limbs with mildly exaggerated jaw jerk, left Babinski sign, and mild decrease of touch and pain sensation in the right C6 and C7 segments. Painful dysesthesia was present in the left hand and right lower limb. The search for serum antibodies against GM1, GM2, GM3, GD1a, Gd1b, GQ1b, GA1, and GT1b was negative. No abnormality except mild cervical spondylotic changes was evident in the magnetic resonance imaging of the brain and spinal cord. The upper limb motor evoked potentials (MEPs) were not elicited by the left cortical stimulation and the central motor conduction time by the right cortical stimulation was remarkably prolonged in the upper limb MEPs. Nerve conduction study showed a delay of motor conduction velocity and distal latency in the right median and bilateral ulnar nerves with low amplitude and delayed velocity of sensory nerves of those nerves. Needle EMG revealed diffuse ongoing denervation potentials in bilateral upper limbs and giant motor unit potentials in the right triceps and first dorsal interossei muscles. These findings indicate that the delayed motor neuron syndrome induced by electrical shock is characteristic for having demyelination as well as axonal changes in both central and peripheral nervous systems.

Aged↗
PubMed1999

Astereopsis caused by traumatic brain injury.

Impaired depth perception (astereopsis) has been observed in a variety of cerebral pathologies affecting the posterior parietal lobe. In the current study of 93 consecutive head trauma admissions, 24% had complete astereopsis and 41% performed more than 2 SDs below the orthopedic control group mean. Degree of impairment was related to Glascow Coma Scale score, length of posttraumatic amnesia, reduced visuospatial and memory abilities, and the presence of intracranial pathology of the parietal lobes. Impairment was also related to trauma severity in patients without any visualized intracranial pathology, presumably due to diffuse axonal shearing. Clinically meaningful impairment was observed in 25% of this group; 10% had complete astereopsis. Stereoacuity screening requires 1 to 2 minutes. Undetected astereopsis may increase risk for subsequent motor vehicle accidents or falls.

Journal Article↗
PubMed2004

Role of purpurin as a retinol-binding protein in goldfish retina during the early stage of optic nerve regeneration: its priming action on neurite outgrowth.

Unlike mammals, the fish optic nerve can regenerate after injury. So far, many growth or trophic factors have been shown as an axon-regenerating molecule. However, it is totally unknown what substance regulates or triggers the activity of these factors on axonal elongation. Therefore, we constructed a goldfish retina cDNA library prepared from the retina treated with optic nerve transection 5 d previously, when it was just before regrowing optic axons after injury. A cDNA clone for goldfish purpurin for which expression was upregulated during the early stage of optic nerve regeneration was isolated from the retina cDNA library. Purpurin was discovered as a secretory retinol-binding protein in developing chicken retinas. Levels of purpurin mRNA and protein transiently increased and rapidly decreased 2-5 d and 10 d after axotomy, respectively. Purpurin mRNA was localized to the photoreceptor cells, whereas the protein was diffusely found in all of the retinal layers. A recombinant purpurin alone did not affect any change of neurite outgrowth in explant culture of the control retina, whereas a concomitant addition of the recombinant purpurin and retinol first induced a drastic enhancement of neurite outgrowth. Furthermore, the action of retinol-bound purpurin was effective only in the control (untreated) retinas but not in those primed (treated) with a previous optic nerve transection. Thus, purpurin with retinol is the first candidate molecule of priming neurite outgrowth in the early stage of optic nerve regeneration in fish.

Amino Acid Sequence↗
PubMed1992

Lesion-induced changes in the production of newly synthesized and secreted apo-E and other molecules are independent of the concomitant recruitment of blood-borne macrophages into injured peripheral nerves.

Peripheral nerve injury produces Wallerian degeneration characterized by a change in the composition of resident nonneuronal cells: macrophages are recruited from the circulation to join Schwann, fibroblast, and endothelial cells. At the same time, the nonneuronal cell population exhibits, as a whole, alterations in synthesis and secretion of diffusible molecules, some of which are instrumental in nerve repair mechanisms. In this study, we determined whether changes in the production of secreted molecules depend on the concomitant modification in cell composition. Therefore, we studied the secretion of newly synthesized molecules by defined cell populations of intact nerves, intact nerve explants undergoing in vitro axonal degeneration, in vivo degenerating nerves, and recruited cells. Nerves were incubated in serum-free, [35S]methionine-containing media. Secreted, radioactively labeled proteins were precipitated from the medium and analyzed by gel electrophoresis. Reduced production of 43-, 46-, and 48-kDa proteins and increased production of 33-34-, 37-, 49-, 59-, and 67-kDa proteins were detected in in situ degenerating nerves. High-density ultracentrifugation and immunoblot analysis revealed that the 33-34-kDa protein is apolipoprotein-E (apo-E). Similar alterations in the production of these molecules were detected in intact nerve explants from which blood-borne cells were excluded. Apo-E, 37-, 49-, 59-, and 67-kDa proteins were also produced in frozen nerves that lacked the intact nerve nonneuronal cell population. Instead, these preparations contained blood-borne cells, primarily macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonium Chloride↗
PubMed2006

Tissue sparing and functional recovery following experimental traumatic brain injury is provided by treatment with an anti-myelin-associated glycoprotein antibody.

Axonal injury is a hallmark of traumatic brain injury (TBI) and is associated with a poor clinical outcome. Following central nervous system injury, axons regenerate poorly, in part due to the presence of molecules associated with myelin that inhibit axonal outgrowth, including myelin-associated glycoprotein (MAG). The involvement of MAG in neurobehavioral deficits and tissue loss following experimental TBI remains unexplored and was evaluated in the current study using an MAG-specific monoclonal antibody (mAb). Anesthetized rats (n=102) were subjected to either lateral fluid percussion brain injury (n=59) or sham injury (n=43). In surviving animals, beginning at 1 h post-injury, 8.64 microg anti-MAG mAb (n=33 injured, n=21 sham) or control IgG (n=26 injured, n=22 sham) was infused intracerebroventricularly for 72 h. One group of these rats (n=14 sham, n=11 injured) was killed at 72 h post-injury for verification of drug diffusion and MAG immunohistochemistry. All other animals were evaluated up to 8 weeks post-injury using tests for neurologic motor, sensory and cognitive function. Hemispheric tissue loss was also evaluated at 8 weeks post-injury. At 72 h post-injury, increased immunoreactivity for MAG was seen in the ipsilateral cortex, thalamus and hippocampus of brain-injured animals, and anti-MAG mAb was detectable in the hippocampus, fimbria and ventricles. Brain-injured animals receiving anti-MAG mAb showed significantly improved recovery of sensorimotor function at 6 and 8 weeks (P<0.01) post-injury when compared with brain-injured IgG-treated animals. Additionally, at 8 weeks post-injury, the anti-MAG mAb-treated brain-injured animals demonstrated significantly improved cognitive function and reduced hemispheric tissue loss (P<0.05) when compared with their brain-injured controls. These results indicate that MAG may contribute to the pathophysiology of experimental TBI and treatment strategies that target MAG may be suitable for further evaluation.

Animals↗
PubMed1983

Elimination of root regeneration in studies of spinal cord regeneration.

In experimental studies of spinal cord regeneration, dorsal root regeneration can be erroneously interpreted as regeneration of the central axons. The present study explored the possibility of eliminating root regeneration by preliminary bilateral division of the L-1 and L-2 roots. Clinical performance as measured by the inclined plane technique showed that root transection significantly reduced motor function (p less than 0.01). As expected, root transection produced atrophic changes in the dorsal columns of the spinal cord, but in some animals there were more diffuse changes in the spinal cord, possibly due to a vascular injury. Thus, root transection is not a good adjunct to regeneration of the spinal cord because the procedure induces deleterious clinical and histologic effects.

Animals↗
PubMed2004

Temporal and spatial patterns of Kv1.1 and Kv1.2 protein and gene expression in spinal cord white matter after acute and chronic spinal cord injury in rats: implications for axonal pathophysiology after neurotrauma.

After spinal cord injury (SCI), surviving white matter axons display axonal dysfunction associated with demyelination and altered K+ channel activity. To clarify the molecular basis of posttraumatic axonal pathophysiology after SCI, we investigated the changes in expression and distribution of the axonal K+ channel subunits Kv1.1 and Kv1.2 in spinal cord white matter after in vivo SCI in the rat. Using Western blot analysis, we found an increased expression of Kv1.1 and Kv1.2 at 2 and 6 weeks after SCI. By real-time PCR we observed an increase in Kv1.1 and Kv1.2 mRNA levels 1 day after SCI, which persisted until 6 weeks. Confocal immunohistochemistry showed a markedly dispersed labelling of Kv1.1 and Kv1.2 along the injured axons, in contrast to the tight localization of these channels to the juxtaparanodes of noninjured axons. This redistribution of Kv1.1 and Kv1.2 occurred as early as 1 h postinjury along some injured axons, and persisted at 6 weeks postinjury. In parallel with the redistribution of Kv1.1 and 1.2, contactin-associated protein (Caspr), which is normally confined to a paranodal location, also displayed a more diffuse distribution along the injured spinal cord axons. Our results suggest that the increased expression of Kv1.1 and Kv1.2 proteins is transcriptionally regulated. In contrast, the redistribution of the axonal K+ channel subunits occurs very early postinjury and probably reflects a disruption of the juxtaparanodal axonal region due to physical trauma, as shown by altered localization of Caspr.

Actins↗
PubMed2005

Nitric-oxide-directed synaptic remodeling in the adult mammal CNS.

In adult mammals, learning, memory, and restoration of sensorimotor lost functions imply synaptic reorganization that requires diffusible messengers-mediated communication between presynaptic and postsynaptic structures. A candidate molecule to accomplish this function is the gaseous intercellular messenger nitric oxide (NO), which is involved in synaptogenesis and projection refinement during development; however, the role of NO in synaptic reorganization processes in adulthood remains to be established. In this work, we tested the hypothesis that this free radical is a mediator in the adult mammal CNS synaptic remodeling processes using a model of hypoglossal axonal injury recently developed by us. Axonal injury-induced disconnection of motoneurons from myocytes produces withdrawal of synaptic inputs to motoneurons and concomitant upregulation of the neuronal isoform of NO synthase (NOS-I). After recovery of the neuromuscular function, synaptic coverage is reestablished and NOS-I is downregulated. We also report, by using functional and morphological approaches, that chronic inhibition of the NO/cGMP pathway prevents synaptic withdrawal evoked by axon injury, despite the persistent muscle disconnection. After successful withdrawal of synaptic boutons, inhibition of NO synthesis, but not of cGMP, accelerated the recovery of synaptic coverage, although neuromuscular disconnection was maintained. Furthermore, protein S-nitrosylation was upregulated after nerve injury, and this effect was reversed by NOS-I inhibition. Our results suggest that during synaptic remodeling in the adult CNS, NO acts as a signal for synaptic detachment and inhibits synapse formation by cGMP-dependent and probably S-nitrosylation-mediated mechanisms, respectively. We also suggest a feasible role of NO in neurological disorders coursing with NOS-I upregulation.

Animals↗
PubMed1981

On the mechanism of the uptake of horseradish peroxidase into the retrograde transport system of ligated postganglionic sympathetic nerves in vitro.

The mechanism of the uptake of horseradish peroxidase (HRP) by damaged post-ganglionic sympathetic axons was studied in vitro. HRP was applied to the damaged axons at the time of nerve injury or after a 3 hours or 17 hours delay. An interval of 3 hours or 17 hours between nerve injury and exposure to HRP had no effect on the localisation of the HRP in the damaged axons or on its retrograde transport to their perikarya. Evidence was found for the pinocytotic uptake of the enzyme by the damaged axons and its accumulation within those axons in elongated cisternae and larger rounded vesicles. In further experiments the damaged axons were treated with HRP at 0 degrees C and then washed in HRP-free medium. The tracer entered the axons in a diffuse form under these conditions but no pinocytotic uptake was observed. However, following 24 hours further incubation at 37 degrees C, HRP could not be found in the perikarya. Treatment at 0 degrees C did not produce any lasting damage to the retrograde transport mechanism. The results of these experiments are compatible with the involvement of pinocytosis in the uptake of HRP in a form suitable for retrograde transport.

Animals↗
PubMed2006

Acute heroin-related neuropathy.

Heroin-related peripheral nervous injury has scarcely been reported, mostly as compressive neuropathy. Rarely, other types of peripheral nervous system (PNS) injury have been recognized, such as plexopathy, polyradiculopathy, mononeuropathy, and rhabdomyolysis. These complications are usually not related to local trauma, but the nature of nerve injury remains unknown. Immunologic mechanisms have been proposed, although generally there is no laboratory evidence of inflammation and usually there is no improvement following steroid therapy. We describe six patients who developed acute PNS injury following intravenous or intranasal heroin self-administration with no evidence of compression injury or inflammation. Four patients had plexopathy (two lumbosacral and two brachial), and two had symmetric distal axonal sensorimotor neuropathy affecting the lower extremities. Of the six patients, five had concomitant rhabdomyolysis (creatine kinase, CK: 5,000-100,000 U/l) and one patient with brachial plexopathy had normal CK levels. The neurological deficit was noticed 3-36 h after heroin administration. Electromyography in five patients was consistent with sensorimotor axonal loss either confined to the affected plexus or with a diffuse distribution in the legs in the two patients with neuropathy. We propose that a toxic mechanism may be responsible for non-compression cases of acute neuropathy following heroin abuse.

Adult↗
PubMed1990

Lesion-induced synthesis and secretion of proteins by nonneuronal cells resident in frog peripheral nerve.

Transection of a peripheral nerve results in Wallerian degeneration of the nerve segment distal to the lesion site and the initiation of axonal regeneration just proximal to it (neuroma site). Nonneuronal cells resident in peripheral nerve are suggested to play an important role in neural repair mechanisms through diffusable molecules that they synthesize and secrete. We examined the array of proteins synthesized and secreted by nonneuronal cells resident in the frog peripheral nerve, which is known for its high regenerative capacity. Nerve segments were incubated in medium containing [35S]methionine, and the secreted radioactively labeled proteins were analyzed by gel electrophoresis. Nerve injury resulted in the complete down-regulation of a group of proteins synthesized and secreted by nonneuronal cells in intact nerve. At the same time, the synthesis and secretion of several proteins were up-regulated in the neuroma and degenerating nerve segments, proximal and distal to the axotomy site, respectively. Proteins secreted by the proximal segment were of apparent kDa/pI (mass/isoelectric point) values of 215/5.6, 76/6.7, 73/7.0, 44/5.2, 36.5/5.6, 35.5/6.0, and 32/6.0. Similar proteins were secreted by the degenerating distal segment but with the exception of variable reductions in the 44- and 32-kDa proteins and increases in proteins of apparent kDa/pI values of 39/5.2 and 29/7.3-7.4. Step gradient ultracentrifugation suggested that the latter two are apolipoproteins. Comparison with plasma apolipoproteins further indicated that nerve and plasma apolipoproteins differ. The up-regulation of the synthesis and secretion of these proteins concurrently with nerve degeneration and regeneration strongly imply that these molecules are involved in neuronal repair mechanisms.

Animals↗
PubMed2003

Ex vivo MR determined apparent diffusion coefficients correlate with motor recovery mediated by intraspinal transplants of fibroblasts genetically modified to express BDNF.

The purpose of this study was to determine whether apparent diffusion coefficients (ADCs) in ex vivo spinal cord white matter, calculated from diffusion weighted MR (DWI) images, correlate with axonal growth and behavioral recovery following subtotal hemisection and transplantation of fibroblasts genetically modified to express brain derived neurotrophic factor (BDNF). These genetically modified fibroblasts have been shown to promote axonal growth, diminish retrograde degenerative changes in axotomized Red nucleus neurons, and are associated with behavioral recovery. Since changes in ADC appear to reflect damage to axons and myelin sheaths, which conventional MR techniques do not identify, partial repair mediated by BDNF-secreting fibroblasts should be detected with ADC measures. Accordingly, we transplanted unmodified fibroblasts (Fb-UM) or fibroblasts modified to secrete BDNF (Fb-BDNF) into cervical subtotal hemisection cavities in adult rats. Rats with Fb-BDNF transplants showed significantly greater behavioral recovery over 12 weeks, as measured by tests of forelimb exploration and open field locomotor activity. Lesion sizes and transplant survival did not differ between the two groups, but immunocytochemical examination showed substantial growth of axons into the Fb-BDNF grafts and little growth into the Fb-UM grafts. Fixed spinal cords were imaged in a 9.4-T magnet. ADCs perpendicular (tADC) and parallel (lADC) to the long axis of the cord were measured in the dorsal lateral white matter, rostral and caudal to the transplant. tADC values and anisotropy index (AI = tADC/lADC) were elevated in both transplant types, indicating white matter damage, but were closer to normal in rats with Fb-BDNF, consistent with known neuroprotection and axonal growth elicited by BDNF. Closer to normal tADC and AI values correlated with improved behavioral recovery. These findings suggest that high-resolution imaging with measurement of tADC and lADC can provide a measure of functionally significant repair that may otherwise go undetected with conventional MR techniques.

Animals↗
PubMed1992

Axotomized frog sciatic nerve releases diffusible neurite-promoting factors.

Using the bullfrog (Rana catesbeiana) dorsal root ganglia (DRG) and its sciatic nerve (ScN) as a model system, we have previously described neuronal and non-neuronal molecular changes associated with the early regenerative response of DRG neurons to axotomy. Since diffusible molecular factors, released by axotomized ScN, might function to stimulate axon regrowth, we have assayed the ability of ScN-conditioned bath to promote in vitro neurite outgrowth from PC-12 cells. Diffusible ScN proteins were collected by incubating segments of normal or axotomized ScN in a small volume of RPMI media for 4 h (nerve bath). The nerve baths, supplemented with serum, were then added to PC-12 cell cultures to assay for the presence of neurite growth factors released by ScN. Results showed that nerve baths, collected from sham-operated or axotomized ScN, could not induce the differentiation of PC-12 into neurite-bearing cells. Therefore, in all subsequent neurite growth assay experiments, an exogenous source of nerve growth factor (NGF) (50 ng/ml) was added to the nerve baths or unconditioned media to generate and maintain PC-12 neuritic structure. We found that nerve baths, collected from previously axotomized (at least 3 days post-injury) nerve, contained diffusible factors which enhanced PC-12 neurite growth, relative to unconditioned media. No neurite growth factors were observed to be released by sham-operated ScN or 1-day post-axotomized ScN. Further experiments were conducted to identify the diffusible neurite growth factors released from axotomized ScN. We showed that the release (if any) of endogenous diffusible NGF or laminin from axotomized nerve could not have accounted for the facilitation of neurite growth. Analysis of radiolabelled ScN proteins by two-dimensional polyacrylamide gel could not have accounted for the facilitation of neurite growth. Analysis of radiolabelled ScN proteins by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) showed that the relative abundance of two diffusible proteins (M(r) approximately 35 and 70 kDa) in the nerve bath was directly correlated with the ability of the nerve bath to facilitate PC-12 neurite growth.

Animals↗
PubMed1987

Evolution of tissue damage in compressive spinal cord injury in rats.

The evolution of tissue damage in compressive spinal cord injuries in rats was studied using an immunohistochemical technique and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The rupture of small vessels accompanied by intense tissue permeation of serum components in and around the hemorrhagic foci appeared to be immediate consequences of the mechanical insult. The loss of cell membrane integrity in neural elements became evident within 1 hour after injury as shown by the diffuse albumin-immunoreactivity of the cytoplasm. At the site of mechanical insult, approximately 30% of the neurofilament proteins were degraded within 1 hour, and 70% of them were lost within 4 hours after injury. A large number of cells positive for glial fibrillary acidic protein were found to demarcate the injured tissue within 1 hour after injury. The progression of tissue damage largely subsided within 48 hours. One week after injury, severe degeneration of the ascending tracts in the posterior funiculus was shown clearly by axon staining and less convincingly by myelin staining. Secondary degeneration of the corticospinal tract in distal segments remained inconspicuous for up to 3 months.

Animals↗
PubMed1996

The neuronal cytoskeleton: an insight for neurosurgeons.

The cytoskeleton is important in the structure and function of the neuron. Disruption of the cytoskeletal proteins occurs in a variety of forms of acute brain injury including cerebral ischaemia and diffuse anonal injury. The final common pathway mediating neuronal cell death involves loss of the integrity of the cytoskeleton and these disturbances may have a key role in the progression of events following acute brain injury. This review aims to provide an insight into the neuronal cytoskeleton in the normal state and in disorders encountered in neurosurgical practice.

Axons↗
PubMed1981

The temporo-spatial course of degeneration after cutting cortico-cortical connections in adult rats.

Adult albino rats received callosotomies or lesions in the paracingular cortex. Between 12 h and 3 months after injury the structure and topography of the degeneration products were studied by light- and electron-microscopy. The degeneration process was quantified by television-image analysis applied to sections prepared according to a new technique that stains reliably degenerating terminals and lysosomes (Gallyas et al. 1980). All types of cortico-cortical connections show a multiphasic degeneration process: During a precursor stage a small number of dense bodies and mitochondrial granules are stained. These and the few early degenerating axon terminals are much more diffusely distributed than the large number of terminals that degenerate during the following period. The terminal degeneration shows a biphasic time course. One maximum appears at 2-7 days post operation, which corresponds to the well known direct consequence of axotomy. The second peak at 10-20 days post operation could be caused by transneuronal reorganization of the cortical connectivity. Terminal degeneration always begins along the borders between cortical regions and areas, but it may change its laminar and columnar distribution pattern during the second phase. The degeneration products that are phagocytosed by astrocytes seem to be removed by intracellular transport to their perivascular endfeet. The degeneration process ends with fiber degeneration which, especially in laminae I and VI, may form a separate peak after 20 days or more.

Animals↗