嗅鞘细胞移植修复大鼠脊髓损伤的组织病理学变化☆

背景：对于脊髓损伤,目前临床尚无有效的治疗对策,近年来嗅鞘细胞移植对脊髓损伤修复取得了一定的进展。 目的：观察嗅鞘细胞移植在缓解损伤脊髓的病理反应和超微结构变化,及其在发生发展中的作用。 方法：60只大鼠随机分为空白组,模型组,嗅鞘胞移植组和DF12组,每组15只。空白组：仅切开T10全椎板及T9,T11部分椎板,对脊髓未作其他处理,明胶海绵轻柔压迫止血;模型组：仅切断脊髓,未作特殊处理;嗅鞘细胞移植组和DF12组：切断脊髓后用微量注射器分别注射嗅鞘细胞和DF12培养液,随后缝合切口。脊髓损伤后1,3,7,14,28,42,56 d每组麻醉2只受检大鼠,取材做光镜观察和电镜观察。 结果与结论：单纯脊髓横切损伤后,发生了出血、水肿、变性、坏死以及囊腔形成,胶质细胞增生和神经纤维再生。嗅鞘细胞移植后,明显减轻了神经元和神经纤维的坏死变性程度,减轻病理反应,并能对损伤神经元实施保护;防止了胶质细胞过度增生形成瘢痕屏障,明显增加了再生神经纤维的数量。提示嗅鞘细胞移植对损伤脊髓具有减轻病理反应和促进修复的作用。     

A-fiber sprouting in spinal cord dorsal horn is attenuated by proximal nerve stump encapsulation

Peripheral nerve transection in the rat alters the spinal cord dorsal horn central projections from both small and large DRG neurons. Injured neurons with C-fibers exhibit transganglionic degeneration of their terminations within lamina II of the spinal cord dorsal horn, while peripheral nerve injury of medium to large neurons induces collateral sprouting of myelinated A-fibers from lamina I and III/IV into lamina II in rats, cats, and primates. To date, it is not known what sequelae are responsible for the collateral sprouting of A-fibers after peripheral nerve injury, although target-derived factors are thought to play an important role. To determine whether target-derived factors are necessary for changes in A-fiber laminar terminations in rat spinal cord dorsal horn, we unilaterally transected the sciatic nerve and ensheathed the proximal nerve stump in a silicone cap. Three days before sacrifice of rat, the injured sciatic nerve was injected with cholera toxin beta-subunit conjugated to horseradish peroxidase (betaHRP) that effectively labels both peripheral and central A-fiber axons. The effect of the ligature, axotomy, and silicone cap treatment was evaluated by analyzing the extent of betaHRP-, Substance P-(SP-), and isolectin B4- (IB4-) immunoreactive (ir) fibers in the somatotopically appropriate spinal cord dorsal horn regions. In all animals, 2-5 weeks after nerve transection (treated or otherwise), IB4- and SP-ir is absent from lamina II. Animals without nerve cap treatment exhibited robust fiber sprouting into lamina II at 2 weeks. In sharp contrast, animals treated with silicone caps did not exhibit betaHRP-ir fibers in lamina II at 2 weeks. This observation was extended up to 5 weeks postinjury. These results suggest that axotomy-induced expansion of betaHRP-ir primary afferent central terminations in the spinal cord dorsal horn is dependent on factors produced in the injury site milieu. While our understanding of local repair mechanisms of injured peripheral nerves is incomplete, it is clear that the time-dependent production of growth factors in the nerve injury microenvironment favor nerve fiber outgrowth, both peripherally and centrally.     

嗅鞘细胞移植损伤脊髓组织的超微结构变化

背景：脊髓损伤后神经功能难以自行恢复,嗅鞘细胞具有外周性和中枢性两种胶质细胞的成鞘功能,是修复受损神经最有前途的种子细胞。嗅鞘细胞移植到受损脊髓后的组织学和超微结构的变化可能帮助解释嗅鞘细胞发挥修复作用的机制。 目的: 验证嗅球源性嗅鞘细胞移植对脊髓损伤功能恢复的促进作用,并观察移植的嗅鞘细胞对神经元和轴突组织和超微结构的影响。 方法：将已制备脊髓模型的Wistar大鼠随机分为3组,对照组不做任何注射操作,DMEM/F12组注射DMEM/F12培养基,嗅鞘细胞组注射嗅鞘细胞悬液。每周进行肢体活动BBB评分,8周后取脊髓标本进行组织学和免疫组织化学观察,评价脊髓损伤的修复情况,并观察嗅鞘细胞移植对脊髓组织和超微结构的影响。 结果与结论：3组动物均出现后肢运动功能的恢复,嗅鞘细胞组优于对照组和DMEM/F12组,在4周后更为明显。组织学观察可见,在嗅鞘细胞组可见有神经纤维通过损伤处。损伤处附近,嗅鞘细胞组脊髓腹侧的神经纤维和神经元形态较好,损伤较轻。而对照组和DMEM/F12组神经纤维和神经元损害严重。嗅鞘细胞组的caspsase-3阳性细胞数少于对照组和DMEM/F12组。超微结构观察可见,嗅鞘细胞组的神经纤维和细胞形态均优于对照组和DMEM/F12组。结果表明嗅鞘细胞移植对大鼠脊髓损伤修复有明显的促进作用,并可恢复损伤神经的部分功能,对受损神经纤维和神经元有保护作用。     

Delayed myelopathy following lightning strike: a demyelinating process

Summary Although the clinical findings in over 30 cases of delayed myelopathy after electrical injury have been described, there are scantly reports of the pathology of the spinal cord in such cases. We report a case in which progressive myelopathy presented 1 month after electrical injury by lightning strike and death occurred 4 months after injury. The spinal cord showed widespread demyelination of white matter from the medulla to just above the conus medullaris. This consisted of selective degeneration of myelin sheaths without inflammation or injury to axons, other cord components, or nerve roots. Infarction of more circumscribed segments of the thoracic cord where demyelination was greatest was probably due to edema associated with myelin degeneration, causing cord swelling limited by the pia mater. Raised pressure within the cord then resulted in secondary infarction.     

Sciatic nerve stimulation increases the degree of histopathological damage in lumbosacral segments after short lasting spinal cord ischemia in rabbit

To characterize the influence of primary afferent activation on the development of histopathological changes in the spinal cord after reversible ischemia, the left sciatic nerve was stimulated at the intensity of myelinated fibers before, during and for 1 h after 10 min of abdominal aortic ligation in halothane anesthetized rabbits. In control animals, only 10 min of spinal cord ischemia or sciatic nerve stimulation was employed. One hour after reperfusion all animals were perfusion fixed with 4% paraformaldehyde. Histopathological analysis using the suppressive Nauta method revealed significantly higher number of argyrophilic neurons in dorsal horns and in the intermediate zone in animals in which spinal cord ischemia was combined with sciatic nerve stimulation in comparison with the animals with spinal cord ischemia, but without stimulation. These histopathological changes corresponded with signs of irreversible damage analyzed on the ultrastructural level. Stimulation of sciatic nerve, but without ischemia did not evoke any detectable neuronal changes. The data from the present study suggest that increased activity of spinal cord neurons evoked by peripheral nerve stimulation can be an important factor in determining the extent of irreversible damage after short lasting ischemia.     

Extensive proliferation of peripheral type myelin in necrotic spinal cord lesions of multiple sclerosis

Peripheral type "remyelination" in the spinal cord was investigated in a 34-year-old woman with relapsing multiple sclerosis (MS) over 7 years following her initial presentation with myelopathy. Confined to the large necrotizing cord lesions involving the gray matter, there was prominent proliferation of peripheral type myelin, measuring up to one-third of the cross-sectional field of the cord. These nerve bundles with peripheral type myelin, which was devoid of glial fibrillary acidic protein immunoreactivity, consisted of relatively monotonous, small-caliber nerve fibers arranged in parallel along the long axis of the cord. The ratio of the myelin thickness to axonal diameter was not as small as that of the ordinary remyelination. Co-existing abundant neuroma formation indicated exuberant regenerative activity of the peripheral nerves. These findings suggest that the peripheral nerve fibers with their axons originating from nerve roots may enter the necrotic MS cord lesions in such a way as to manifest in spinal cord trauma. Relatively frequent occurrence of this extensive proliferation of peripheral type myelin in Japanese MS subjects appears to be related to the severity of tissue destruction experienced in Japanese as compared with that of occidental MS.     

Contribution of degeneration of motor and sensory fibers to pain behavior and the changes in neurotrophic factors in rat dorsal root ganglion

To elucidate the role of the degeneration of motor and sensory fibers in neuropathic pain, we examined the pain-related behaviors and the changes of brain-derived neurotrophic factor (BDNF) in the L4/5 dorsal root ganglion (DRG) and the spinal cord after L5 ventral rhizotomy. L5 ventral rhizotomy, producing a selective lesion of motor fibers, produced thermal hyperalgesia and increased BDNF expression in tyrosine kinase A-containing small- and medium-sized neurons in the L5 DRG and their central terminations within the spinal cord, but not in the L4 DRG. Furthermore, L5 ventral rhizotomy up-regulated nerve growth factor (NGF) protein in small to medium diameter neurons in the L5 DRG and also in ED-1-positive cells in the L5 spinal nerve, suggesting that NGF synthesized in the degenerative fibers is transported to the L5 DRG and increases BDNF synthesis. On the other hand, L5 ganglionectomy, producing a selective lesion of sensory fibers, produced heat hypersensitivity and an increase in BDNF and NGF in the L4 DRG. These data indicate that degeneration of L5 sensory fibers distal to the DRG, but not motor fibers, might influence the neighboring L4 nerve fibers and induce neurotrophin changes in the L4 DRG. We suggest that these changes of neurotrophins in the intact primary afferents of neighboring nerves may be one of many complex mechanisms, which can explain the abnormal pain behaviors after nerve injury. The ventral rhizotomy and ganglionectomy models may be useful to investigate the pathophysiological mechanisms of neuropathic pain after Wallerian degeneration in motor or sensory or mixed nerve.     

Acute ischemic transection of peripheral axons in angiopathic neuropathy. No demyelination of fasciculus gracilis or decreased number or size of cytons of spinal ganglion neurons.

Demyelination (loss of myelin profiles) of posterior columns of the spinal cord in patients with neuropathy coming to autopsy usually has been interpreted as secondary to distal degeneration of peripheral nerve fibers. Previous experiments to test whether these pathologic changes could result from transecting peripheral nerves produced conflicting results. In a patient with necrotizing angiopathy in whom extensive regions of fiber transection began proximally at midthigh level, the density and diameter distribution of myelinated fibers of the fasciculus gracilis and the number and size distribution of cytons of L3 and L5 spinal ganglia have been obtained and compared with normative measurements. No discernible alteration was found, suggesting that acute degeneration of peripheral nerve fibers is not associated with loss or decrease in size of cytons of spinal ganglia or with loss or decrease in size of myelinated fibers in the fasciculus gracilis.     

Myelopathy induced by lactic acid

Summary This study defines the conditions required to provoke myelopathic changes by dripping lactic acid onto the surgically exposed spinal cord of adult male rats. A severe necrotizing myelopathy was observed after 24 h, principally in the posterior half of the cord at the level of lactic acid (pH 1.8) application. A profound early effect on small blood vessel walls, appearing nerotic after 30 min to 2 h, was identified. Nerve fiber alterations Iaxonal stasis, granular axoplasm, axonal calcification, and vesicular myelin), identical to those appearing early in the myelopathies of trauma and calcium toxicity, were apparent. However, the pathogenesis of these alterations in this model remains unclear, because of the vascular events and the presumed alterations of calcium metabolism by the acid. Further studies are required to elucidate the precise mechanisms of these important reactions of myelinated axons to the injuries provoked by acid, calcium, and trauma.Supported by NIH grant No. NS11066. This work was presented in part at the 60th Annual Meeting of the American Association of Neuropathologists, San Diego, CA; June 1984 (J Neuropathol Exp Neurol 43:324, 1984)     

Does diffusion tensor data reflect pathological changes in the spinal cord with chronic injury？

Magnetic resonance diffusion tensor imaging has been shown to quantitatively measure the early pathological changes in chronic cervical spondylotic myelopathy. In this study, a novel spongy poly- urethane material was implanted in the rat C~-s epidural space to establish a rat model of chronic cervical spondylotic myelopathy. Diffusion tensor data were used to predict pathological changes. Results revealed that the fractional anisotropy value gradually decreased at 4, 24, and 72 hours and 1 week after injury in rat spinal cord, showing a time-dependent manner. Average diffusion coeffi- cient increased at 72 hours and 1 week after implantation. Hematoxylin-eosin staining and Luxol-fast-blue staining exhibited that the number of neurons in the anterior horn of the spinal cord gray matter and the nerve fiber density of the white matter gradually reduced with prolonged com- pression time. Neuronal loss was most significant at 1 week after injury. Results verified that the fractional anisotropy value and average diffusion coefficient reflected the degree of pathological change in the site of compression in rat models at various time points after chronic spinal cord compression injury, which potentially has a reference value in the early diagnosis of chronic cervical spondylotic myelopathy.     

Glial cell reactions in the spinal cord after sensory nerve stimulation are associated with axonal injury

Astroglial and microglial reactions in the dorsal and ventral horns of the adult rat spinal cord were studied after graded electrical stimulation of the rat sciatic nerve and after topical application of mustard oil to the hindlimb foot. Antibodies to glial fibrillary acidic protein and complement receptor 3 (OX-42) were used as markers for astroglia and microglia, respectively. The results showed that electrical nerve stimulation resulted in increased immunoreactivity for GFAP and OX-42 in the spinal cord dorsal and ventral horns only after the use of stimulation strengths which were associated with nerve fiber degeneration in the stimulated nerve. Application of mustard oil to the foot caused no changes in GFAP or OX-42 immunoreactivity. These findings indicate that peripheral nerve stimulation in itself is insufficient to induce astroglial and microglial responses in the spinal cord. The signal(s) mediating these responses, regularly seen after nerve injury, are therefore most probably not related to the afferent barrage of action potentials evoked by the injury.     

嗅鞘细胞移植脊髓损伤大鼠后Semaphorin3A的表达

脊髓损伤后损伤区Semaphorin3A(Sema3A)表达明显升高,嗅鞘细胞移植对此会有何影响？实验发现单纯脊髓横切损伤后,会出现脊髓出血、水肿、变性、坏死,囊腔形成,胶质细胞增生和神经纤维再生等病理反应。嗅鞘细胞移植后,脊髓的上述病理反应明显减轻,损伤区神经元和神经纤维的坏死程度下降,损伤区Sema3A表达降低。证实嗅鞘细胞移植可通过降低Sema3A表达对损伤脊髓神经元起保护作用。     

Neuropathological effects of phenyl saligenin phosphate in chickens

Cyclic phenyl saligenin phosphate (PSP) proved to be a potent delayed neurotoxin, eliciting clinical disease and lesions, and depressing neuropathy target esterase and plasma cholinesterase at much lower doses than the protoxicant tri-ortho-tolyl phosphate (TOTP). Using adult White Leghorn chickens, we noted qualitative similarities in clinical signs and peripheral nerve and spinal cord lesions elicited by PSP and the TOTP. Ataxia and weakness were prominent clinical effects. Lesions began as a distal axonopathy affecting larger myelinated fibers in spinal cord white matter and peripheral nerve. The latter were studied in detail. Major features of the lesion were intra-axonal collections of mitochondria, dense and lamellar bodies, and granular degeneration of neurofilaments. These led to Wallerian-like degeneration. Percentages of teased peripheral nerve fibers demonstrating such degeneration correlated with severity of clinical signs.     

Functional deficits and anatomical alterations after high cervical spinal hemisection in the rat

A recent report by Matinian and Andreasian (1976. Enzyme Therapy in Organic Lesions of the Spinal Cord. Brain Information Service, University of California, Los Angeles) concluded that regeneration of the spinal cord sufficient to restore walking occurred in spinal rats (T5 transection) that had been treated by repeated injections of trypsin and hyaluronidase at the site of the lesion. These enzymes were believed to decrease the intense connective tissue and neuroglial scar which otherwise acts as a mechanical barrier to nerve fiber outgrowth. The present experiment tested whether or not these enzymes might similarly facilitate regeneration and functional restitution of the spinal respiratory pathway. The spinal cord of rats was hemisected at C2 (i.e., rostral to the phrenic nucleus), thereby paralyzing the ipsilateral hemidiaphragm. Hyaluronidase and trypsin were injected at the time of operation, and for 15 days thereafter each enzyme was administered on alternate days. Control animals received injection of vehicle. All injections were given subcutaneously at the site of injury. After 5 to 6 months, diaphragmatic function was assessed by electromyography. The spinal cord was then fixed by perfusion with Bouin's solution and embedded in paraffin, and sections were prepared and stained for connective tissue fibers, glial fibers, and nerve fibers. None of the treated or control animals showed any evidence of diaphragmatic activity on the operated side. In every animal the site of injury was composed of a dense connective tissue scar surrounded by an encapsulating neuroglial scar. Well-oriented nerve fibers grew to the margin of the lesion where they became deflected. A small number of fibers entered the lesion, but none grew across the injured region. These observations do not support the contention that enzyme treatment facilitates regeneration of the injured spinal cord.     

Nociceptive responses and spinal plastic changes of afferent C-fibers in three neuropathic pain models induced by sciatic nerve injury in the rat

Peripheral nerve injuries induce plastic changes on primary afferent fibers and on the spinal circuitry, which are related to the emergence of neuropathic pain. In this study we compared three models of sciatic nerve injury in the rat with different degrees of damage and impact on regeneration capability: crush nerve injury, chronic constriction injury (CCI) and spared nerve injury (SNI). All three models were characterized by means of nerve histology, in order to describe the degenerative and regenerative process of injured axons. Nociceptive responses were evaluated by mechanical and thermal algesimetry tests. Crush animals displayed higher withdrawal thresholds on the ipsilateral paw compared to the contralateral during the time of denervation, while CCI and SNI animals showed mechanical and thermal hyperalgesia. Central plasticity was evaluated by immunohistochemical labeling of non-peptidergic (IB4-positive) and peptidergic (substance P-positive) nociceptive C-fibers on L4-L6 spinal cord sections. After crush nerve injury and SNI, we observed progressive and sustained reduction of IB4 and SP immunolabeling at the sciatic projection territory in the superficial laminae of the dorsal horn, which affected only the tibial and peroneal nerves projection areas in the case of SNI. After CCI, changes on SP-immunoreactivity were not observed, and IB4-immunoreactive area decreased initially but recovered to normal levels on the second week post-injury. Thus, nociceptive responses depend on the type of injury, and the immunoreactivity pattern of afferent fibers at the spinal cord display changes less pronounced after partial than complete sciatic nerve injury. Although signs of neuropathic pain appear in all three lesion models, nociceptive responses and central plasticity patterns differ between them.     

Schedule dependency of paclitaxel-induced neuropathy in mice: a morphological study

Paclitaxel, which is known to induce peripheral neuropathy in humans, was administered to BDF1 mice, and a neuropathological examination was then conducted. Paclitaxel was administered at a dose of 30 mg/kg once or several times at different intervals, 3 times, every 3 hours (q3hx3), every day (q1dx3), every 2 days (q2dx3) and 4 times, once a week (q7dx4). The spinal cord, spinal ganglion and peripheral nerves (sciatic and tibial) were then processed for neuropathological examination following perfusion of the anesthetized mice. The effect on the peripheral nerves was evaluated by counting the number of abnormal nerve fibers in the preparations of teased nerve fibers and in the epoxy resin 1-microm-thick sections. The drug-induced degeneration, such as axonal and myelin fragmentations and phagocytosis in the nerve fibers, was detected in the dorsal funiculus, the dorsal spinal roots and the peripheral nerves (sciatic and tibial). No drug-related degeneration was observed in the motor neurons in the spinal cord nor in the ventral spinal roots. The single treatment did not induce any changes. The severity of the degeneration was as follows: q2dx3>q1dx3>q3hx3 and q7dx4. The degeneration in the mice treated on q3hx3 and q7dx4 was very slight, but it was clear that paclitaxel also induced degeneration on these schedules. These results suggest that paclitaxel induces a predominantly sensory neuropathy in mice and the severity is obviously dependent on the treatment schedule.     

Haloxon-induced delayed neurotoxicity: effect of plasma A (aryl) esterase activity on severity of lesions in sheep

A markedly different response to the delayed neurotoxic effects of a single dose of 400 or 800 mg/kg of the organophosphorus anthelmintic haloxon was observed in two populations of sheep. Animals with a gentically determined low level of activity of the plasma enzyme A (aryl) esterase developed clinical signs of delayed neurotoxicity within one month. Lesions relating to degeneration of myelinated nerve fibers were seen in brain stem, spinal cord, and on occasion peripheral nerve. The incidence of clinical signs, and severity of lesions as determined by semiquantitative morphological study of the spinal cord, were greater in animals given the higher dose. Neither clinical signs nor lesions relating to organophosphate-induced delayed neurotoxicity were seen in sheep with high plasma activity of A esterase.     

Laser Effects on Myelinated and Nonmyelinated Fibers in the Rat Peroneal Nerve: A Quantitative Ultrastructural Analysis

We have recently shown that Nd:YAG laser irradiation of rat peripheral nerve differentially impairs action potential transmission in small, slowly conducting sensory fibers compared to fast conducting afferents. In addition, the number of small sensory neurons of the A-δ- and C-fiber group labeled with HRP is significantly reduced after laser irradiation, while the number of labeled large sensory neurons and motoneurons was not affected. To further evaluate this laser-induced injury, we examined three distinct regions of the laser-irradiated rat peroneal nerve using ultrastructural morphometric methods. These regions were the site of laser irradiation and zones 10 mm proximal and 5 mm distal to the injury. The contralateral nerve was sham treated. Our results indicate that for the small nonmyelinated fibers, there was a significant increase in both mean fiber size and the number of microtubules per fiber, but a decrease in the number of neurofilaments. In contrast, the number of myelinated and nonmyelinated fibers is not significantly altered at 7 days following laser irradiation, and the mean diameter and frequency distribution of myelinated nerve fibers was unchanged. This study demonstrates that selective functional alterations in laser-irradiated nerves (nerve conduction velocity, HRP transport properties) are accompanied by ultrastructural changes of axonal organelles in nonmyelinated fibers. Nd:YAG laser light might ultimately prove to be a powerful tool to selectively alter functional properties in small, slowly conducting afferent fibers, without causing degeneration at the ultrastructural level at the site of irradiation. We hypothesize further that the laser-induced functional alterations might be related to differential thermally mediated changes.     

Olfactory ensheathing cells can reduce the tissue loss but not the cavity formation in contused spinal cord of rats

In recent years, olfactory ensheathing cells (OECs) have been used as a therapeutic strategy to repair the anatomical structure and promote the function recovery of injured spinal cord in both animal and human. In this study, OECs were transplanted into contused spinal cords of adult rats. After dorsal laminectomy at T10 vertebra, spinal cord was injured by a force of 10 g with NYU II impactor from 25 mm above the exposed cord. The contused spinal cord received injections of OECs in DMEM or DMEM alone at one week after injury. The migration and distribution of OECs in the contused spinal cord were observed by the light microscope. The intact tissue area, injured tissue area, cavity size, number of myelinated nerve fibers and neurons labeled by CB-HRP in T8 segment were measured and counted by the semi-quantitative techniques at 6 weeks after transplantation. Locomotor ability and conductive function of the spinal cord were evaluated by the BBB score and cortical somatosensory evoked potentials (CSEP) recording. OECs were found in both lesion site and tissue near the lesion. The intact tissue area was significantly larger in the OECs-transplanted rats than that in the DMEM-injected animals, whereas the injured tissue area was significantly smaller in the OECs-rats than that in the DMEM-rats. The number of myelinated nerve fibers in the lesion site and preserved neurons in T8 was significantly greater in the OECs-group than in the DMEM-group, but the cavity size detected was not significantly different between the two groups. The BBB score and CSEP recording showed a better performance of locomotor ability and conductive function in the OECs-transplanted rats than in the DMEM-injected animals. These results indicate that OECs can counteract secondary tissue degeneration after spinal cord injury. Although they cannot reduce the cavity formation, they can promote morphological preservation and functional improvement of the contused spinal cord.     

Microtubule-associated protein 2 as a sensitive marker for dendrite lesions after spinal cord trauma: an immunohistochemical study in the rat

We evaluated, by irnmunohistochemistry, the changes of microtubule-associated protein 2 (MAP2) of rat spinal cord following compression injury of mild, moderate and severe degrees at the Th8-9 level. The spinal cord of normal rats and animals subjected to laminectomy only, presented immunoreactivity to MAP2 in nerve cell bodies and dendrites but not in axons and other structures. Following moderate and severe compression resulting in reversible paraparesis or irreversible paraplegia, respectively, the compressed segment showed loss of MAP2 immunoreactivity in dendrites and nerve cell bodies already 4 h after injury. This phenomenon remained throughout the experimental period of 9 days. Our findings indicate that there is a rapid and long-lasting reduction of MAP2 in nerve cell bodies and dendrites of the compressed segment and that this alteration is related to the degree of the impact to the cord. The reduction of MAP2 may well have functional implications by interfering with neurotransmission. MAP2 immuno-staining is an excellent way of studying dendritic changes in spinal cord trauma and can be used in future experiments designed to investigate the influence of various therapeutic measures on secondary lesions after trauma.