OBJECTIVETo observe the pathological changes of axonal injury in a rat model of experimental allergic encephalomyelitis (EAE).

METHODSWith HE, luxol fast blue and Bielschowsky staining, the expression of APP, MBP, SMI-32 and MBP in the brain and spinal cord of EAE rats using double-labeling indirect immunofluorescence.

RESULTSExtensive cuffing lesions of inflammatory cell infiltrations were found in the brain and spinal cord of the rats, accompanied by multiple lesions of demyelination, axonal disarrangement with vesicular loss. SMI-32 staining identified numerous nonphosphorylated neurofilament, indicating the presence of axonal injury. Axonal oval bodies formed by APP accumulation were found in the white matters of the spinal cord 14 days after EAE, suggesting that neuraxial damage occurred in the early stage of EAE which was not synchronous with myelin loss.

CONCLUSIONDifferent levels of inflammation occur in different stages of EAE, and inflammatory cell infiltration is the most obvious at the peak of EAE. Axonal injury occurs in the early stage of EAE and progresses over the entire disease course.

Animals ; Axons ; pathology ; Brain ; pathology ; Encephalomyelitis, Autoimmune, Experimental ; pathology ; Female ; Rats ; Rats, Wistar ; Spinal Cord ; pathology

Research on peripheral nervous injuries, especially the stretched injuries, is important to improve the clinical effectiveness and alleviate the patients's pain. In recent years, the biological changes and mechanics of stretched axons have been hot topics. This article reviews the recent advances in the morphological changes of axons as well as changes in cellular membrane, cytoskeleton, cellular metabolism, and action potential after axonal stretch.
Action Potentials ; Animals ; Axons ; metabolism ; pathology ; Cell Membrane ; pathology ; Cytoskeleton ; pathology ; Humans ; Stress, Mechanical

When ischemia or hemorrhagic stroke occurs, astrocytes are activated by a variety of endogenous regulatory factors to become reactive astrocytes. Subsequently, reactive astrocytes proliferate, differentiate, and migrate around the lesion to form glial scar with the participation of microglia, neuron-glial antigen 2(NG2) glial cells, and extracellular matrix. The role of glial scars at different stages of stroke injury is different. At the middle and late stages of the injury, the secreted chondroitin sulfate proteoglycan and chondroitin sulfate are the main blockers of axon regeneration and nerve function recovery. Targeted regulation of glial scars is an important pathway for neurological rehabilitation after stroke. Chinese medicine has been verified to be effective in stroke rehabilitation in clinical practice, possibly because it has the functions of promoting blood resupply, anti-inflammation, anti-oxidative stress, inhibiting cell proliferation and differentiation, and benign intervention in glial scars. This study reviewed the pathological process and signaling mechanisms of glial scarring after stroke, as well as the intervention of traditional Chinese medicine upon glial scar, aiming to provide theoretical reference and research evidence for developing Chinese medicine against stroke in view of targeting glial scarring.
Astrocytes ; Axons/pathology* ; Cicatrix/pathology* ; Gliosis/pathology* ; Humans ; Medicine, Chinese Traditional ; Nerve Regeneration ; Stroke/drug therapy*

Spinal cord injury (SCI) disrupts the structural and functional connectivity between the higher center and the spinal cord, resulting in severe motor, sensory, and autonomic dysfunction with a variety of complications. The pathophysiology of SCI is complicated and multifaceted, and thus individual treatments acting on a specific aspect or process are inadequate to elicit neuronal regeneration and functional recovery after SCI. Combinatory strategies targeting multiple aspects of SCI pathology have achieved greater beneficial effects than individual therapy alone. Although many problems and challenges remain, the encouraging outcomes that have been achieved in preclinical models offer a promising foothold for the development of novel clinical strategies to treat SCI. In this review, we characterize the mechanisms underlying axon regeneration of adult neurons and summarize recent advances in facilitating functional recovery following SCI at both the acute and chronic stages. In addition, we analyze the current status, remaining problems, and realistic challenges towards clinical translation. Finally, we consider the future of SCI treatment and provide insights into how to narrow the translational gap that currently exists between preclinical studies and clinical practice. Going forward, clinical trials should emphasize multidisciplinary conversation and cooperation to identify optimal combinatorial approaches to maximize therapeutic benefit in humans with SCI.
Humans ; Axons/pathology* ; Nerve Regeneration/physiology* ; Spinal Cord Injuries/therapy* ; Neurons/pathology* ; Recovery of Function

Brainstem of rats were stabbed with a needle and pathological changes of neurons and axons in brainstem were observed at different time after injury with Nissl's body staining, silver staining and modified trichrome staining. It was found that, by silver staining, the axons showed irregular swelling and disconnection at 1-3 h, marked swelling of the severe end at 6 h, retraction ball at 15 h and remarkable retraction ball at 24 h. By modified trichrome staining, the space between myelin sheaths and axons was widened at 3-6 h, and tortuous myelin sheaths adhered incompletely on axons, or even peeled off at 15 h to 24 h. Perinuclear lysis of Nissl's bodies at 24 h after injury could be seen by Nissl body staining. The results indicated that, the pathological changes in injured brainstem could be observed with histochemical staining, which might be used for timing brainstem injuries.
Animals ; Axons/pathology* ; Brain Injuries/pathology* ; Brain Stem/injuries* ; Female ; Histocytochemistry ; Male ; Neurons/pathology* ; Rats ; Rats, Wistar ; Staining and Labeling

Cortical dysplasia (CD) is considered to be a malformative lesion of the neocortex which exhibits a spectrum of pathologic changes reflecting a disturbance in the process of its development. CD is recently recognized as a major cause of intractable epilepsy with non-neoplastic lesions. Mischel et al. proposed that CD can be graded mild, moderate and severe with regard to nine specific microscopic abnormalities: mild CD consists of 1) cortical laminar disorganization, 2) single heterotopic white matter neurons, 3) neurons in the cortical molecular layer, 4) persistent remnants of the subpial granular cell layer, and 5) marginal glioneuronal heterotopia; moderate CD displays 6) polymicrogyria and 7) white matter neuronal heterotopia; severe CD phows 8) neuronal cytomegaly with associated cytoskeletal abnormalities and 9) balloon cell change. We reassessed 71 cases of cortical dysplasia to elucidate the proportion and histologic features of each group, using Mischel's grading system. CD was most frequently found in the temporal lobe with 50 cases (70%). Mild CD was predominently seen and was noted in 61 cases (86%) Cortical laminar disorganization and single heterotopic white matter neurons were identified in all mild CD cases. Neurons in the cortical molecular layer, persistent subpial granular cell layer, and marginal glioneuronal heterotopia were also noted in case numbers 40, 3, and 1 of mild CD, respectively. Moderate CD was composed of 2 cases with polymicrogyria, and the remaining 8 cases had severe CD. All moderate and severe CD were associated with the various histological features of mild CD. Thirty eight cases (51%) of CD showed dual pathology, composed of both CD and hippocampal sclerosis, and 5 cases of dysembryoplastic neuroepithelial tumor also had CD. Neurofilament immunostain revealed disarray of abnormally beaded axons in CD. We believe that the grading system of CD is very important to the evaluation and classification of CD.
Axons ; Classification ; Epilepsy ; Malformations of Cortical Development* ; Neocortex ; Neoplasms, Neuroepithelial ; Neurons ; Pathology ; Sclerosis ; Temporal Lobe

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron degenerative disease that clinically manifests both upper and lower motor neuron signs. However, it is unknown where and how the motor neuron degeneration begins, and conflicting hypotheses have been suggested. Recent advanced radiological techniques enable us to look into ALS neuropathology in vivo. Herein, we report a case with upper motor neuron-predominant ALS in whom the results of brain magnetic resonance imaging (MRI) and myelin water fraction MRI suggest axonal degeneration.
Amyotrophic Lateral Sclerosis* ; Axons ; Brain ; Magnetic Resonance Imaging* ; Motor Neurons ; Myelin Sheath* ; Neuropathology ; Pathology ; Water*

BACKGROUND: Diabetic neuropathy is one of the most common neuropathies. Although pathologic studies show both segmental demyelination and axonal loss in diabetic neuropathy, the relative importance of segmental demyelination is debated. Conduction block (CB) is a physiologic hallmark of segmental demyelination. If segmental demyelination were a main pathology of diabetic neuropathy, CB should be common. We undertook this study to determine the prevalence of CB in diabetic patients. METHODS: Fifty-two consecutive diabetic patients (M=30, F=22) were referred to EMG laboratory and underwent routine nerve conduction studies (NCS). CB was defined by two methods. One was > 20% drop in peak-to-peak amplitude and < 15% change in negative-peak duration between proximal and distal stimulation sites. The other was > 50% drop in the amplitude and area. Clinical findings, electrophysiological data, and effectiveness of immunomodulating therapy for some patients with CB were reviewed. RESULTS: A total 326 nerves were studied. The criteria for 20% and 50% CB were met in 35 nerves in 19 patients and 7 nerves in 6 patients, respectively (prevalence=10.7%, 2.1%, respectively). Some patients with CB were treated with IVIG or steroid and had a good response. CONCLUSIONS: CB in diabetic neuropathy is not a common finding. The rarity of CB in diabetic neuropathy suggests that segmental demyelination is not a prominent part of the underlying pathology. The presence of CB and good responsiveness to immunomodulating therapy in diabetic neuropathy also suggest alternative or additional causes for neuropathy, such as chronic inflammatory demyelinating polyneuropathy.
Axons ; Demyelinating Diseases* ; Diabetes Mellitus ; Diabetic Neuropathies* ; Humans ; Immunoglobulins, Intravenous ; Neural Conduction ; Pathology ; Polyneuropathies ; Prevalence

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) represents an important acquired condition characterized by progressive, symmetrical, proximal and distal weakness. CIDP is characterized by sensory loss and weakness, areflexia, elevated CSF protein and electrodiagnostic evidence of multifocal demyelination with or without superimposed axonal degeneration. Some reports are made that an antecedent illness in the weeks preceding the onset of symptoms such as upper respiratory syndrome or flu-like illness, gastrointestinal syndrome etc., but intestinal pseudoobstruction as the main clinical feature in CIDP is an uncommon finding. The clinical course is variable. The condition is responsive to immunosuppressive therapy, especially prednisone and plasma exchange. We report a case of intestinal pseudoobstruction secondary to CIDP diagnosed by clinical features, electrodiagnostic study and nerve biopsy pathology.
Axons ; Biopsy ; Demyelinating Diseases ; Intestinal Pseudo-Obstruction* ; Pathology ; Plasma Exchange ; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating* ; Prednisone

It has been well established that the recovery ability of central nervous system (CNS) is very poor in adult mammals. As a result, CNS trauma generally leads to severe and persistent functional deficits. Thus, the investigation in this field becomes a "hot spot". Up to date, accumulating evidence supports the hypothesis that the failure of CNS neurons to regenerate is not due to their intrinsic inability to grow new axons, but due to their growth state and due to lack of a permissive growth environment. Therefore, any successful approaches to facilitate the regeneration of injured CNS axons will likely include multiple steps: keeping neurons alive in a certain growth-state, preventing the formation of a glial scar, overcoming inhibitory molecules present in the myelin debris, and giving direction to the growing axons. This brief review focused on the recent progress in the neuron regeneration of CNS in adult mammals.
Animals ; Axons ; physiology ; Central Nervous System Diseases ; complications ; metabolism ; pathology ; Humans ; Mammals ; physiology ; Nerve Regeneration ; physiology