Impairment induction by axotomy in motor functional and histological anterior horn of spinal cord structure / Inducción del deterioro por axotomía en la estructura motora funcional e histológica del asta anterior de la médula espinal

We have surveyed the motor changes in rats subjected to sciatic nerve axotomy. The rats were divided into two groups, each one consisting of ten animals, which underwent the following intervention: The first group (control): healthy rats without any injuries and experimental group: rats with injured sciatic nerve without treatment. at 12 weeks, the L4 and L5 spinal cord segments were removed. We evaluated nerve function using muscle electromyography (EMG) activity and sciatic function index (SFI) simultaneously with histological spinal cord analyses by stereological methods at 12 week. After nerve injury presented gross locomotor deficits at week 12. We also found that the volume of the anterior horn of spinal cord and total number of motor neurons were decreased after nerve axotomy (p<0.05). In conjunction, these results indicate that peripheral nerve injuries have more severe consequences on hind limb motor output.

En este estudio se examinaron los cambios motores en ratas sometidas a axotomía del nervio ciático. Las ratas se dividieron en dos grupos diez animales. El primer grupo (control) eran ratas sanas sin lesiones, y el grupo experimental consistió en ratas con nervio ciático lesionado sin tratamiento. A las 12 semanas, los segmentos de la médula espinal L4 y L5 fueron removidos. Se evaluó la función nerviosa mediante electromiografía muscular (EMG) y el índice de función ciática (IFC), simultáneamente con análisis histológicos de la médula espinal mediante métodos estereológicos. A las 12 semanas de la lesión nerviosa presentó déficit locomotor grueso. Además, se observó que el volumen del asta anterior y el número total de neuronas motoras disminuyeron después de la axotomía nerviosa (P <0,05). En conjunto, estos resultados indican que las lesiones de los nervios periféricos determinan graves consecuencias de la función motora de los miembros posteriores.

Lethal Cardiac Complications in a Long-Term Survivor of Spinal Muscular Atrophy Type 1 / 고신대학교의과대학학술지

Spinal muscular atrophy (SMA) is a rare neuromuscular disease characterized by degeneration of the anterior horn cells of the spinal cord and motor nuclei in the lower brainstem, resulting in hypotonia, progressive proximal muscle weakness, paralysis, and progressive respiratory insufficiency. We report the case of a 6-year-old girl diagnosed with spinal muscular atrophy type 1 (Werdnig-Hoffman disease) who has been treated at home with non-invasive ventilation (assist-control mode with a back-up respiratory rate of 26 per minute). She presented with an atrioventricular block and atrial fibrillation, as well as paroxysmal fluctuation of blood pressure and heart rate indicating autonomic dysfunction. Although it is known that patients with spinal muscular atrophy type 1 do not generally demonstrate cardiac problems, it can be concluded based on findings in our case that long-term survivors with spinal muscular atrophy type 1 may develop cardiac rhythm disturbances. We therefore recommend that the possibility of cardiac complications and autonomic dysfunction should be borne in mind in the management of such patients.

Clinical Experiences of Uncommon Motor Neuron Disease: Hirayama Disease

Hirayama disease, juvenile muscular atrophy of the distal upper limb, is a rare disease predominantly affecting the anterior horn cells of the cervical spinal cord in young men. This cervical myelopathy is associated with neck flexion. It should be suspected in young male patients with a chronic history of weakness and atrophy involving the upper extremities followed by clinical stability in few years. Herein, we report 2 cases of Hirayama disease on emphasis of diagnostic approach and describe the pathognomonic findings at flexion magnetic resonance imaging.

Prolonged Motor Weakness With Syringomyelia in Japanese Encephalitis: A Case Study

Japanese encephalitis (JE) shows characteristic brain lesions, including bilateral thalamus, midbrain, internal capsule, basal ganglia, and occasionally involves an anterior horn cell. We encountered a case of a 44-year-old man who initially presented with encephalitis, which was finally diagnosed as Japanese encephalomyelitis with syringomyelia. The patient showed severe motor weakness followed by delayed recovery of functional motor activities. Cervical magnetic resonance imaging showed syrinx formation at the C5 level suggesting myelitis, and abnormal electromyographic findings were noted. Clinicians should consider the possibility that the spinal cord may be involved; an example would be syringomyelia due to myelitis in a case of JE presenting with severe and prolonged motor weakness.

Effect of alcoholic extract of Nigella sativa seed on alpha motor neurons density of spinal cord following sciatic nerve compression in rats

Compression or sciatic axotomy induces neuronal death in spinal cord alpha motor neuron. This study was carried out to determine the effect of Nigella sativa seed alcoholic extract on spinal motor neuron density in anterior horn after sciatic nerve compression in rat. In this experimental study 24 wistar rats were divided into four groups A: control, B: compression, C: compression+treatment with 75 mg/kg alcoholic extract, D: compression+treatment with 50 mg/kg alcoholic extract. In control group muscle was exposed without any injury to sciatic nerve. In compression and treatment group, the right leg sciatic nerve compressed for 60 sec. After four weeks of post operation, L2-L4 and S1, S2 and S3 segments of spinal cord were sampled, processed, serially sectioned and stained with toluidine blue. The number of alpha motor neurons was counted using dissector method. Neuronal density in compression group [650 +/- 32] significantly decreased in comparison with control group [1803 +/- 24]. Neuronal density in C treated group [1581 +/- 47] and D treated group [1543 +/- 49] significantly increased compare to compression group [P<0.001]. Alcoholic extract of Nigella sativa seed increased the density of alpha motor neurons in spinal cord after sciatic nerve compression in rats

The Puzzling Case of Hyperexcitability in Amyotrophic Lateral Sclerosis

The development of hyperexcitability in amyotrophic lateral sclerosis (ALS) is a well-known phenomenon. Despite controversy as to the underlying mechanisms, cortical hyperexcitability appears to be closely related to the interplay between excitatory corticomotoneurons and inhibitory interneurons. Hyperexcitability is not a static phenomenon but rather shows a pattern of progression in a spatiotemporal aspect. Cortical hyperexcitability may serve as a trigger to the development of anterior horn cell degeneration through a 'dying forward' process. Hyperexcitability appears to develop during the early disease stages and gradually disappears in the advanced stages of the disease, linked to the destruction of corticomotorneuronal pathways. As such, a more precise interpretation of these unique processes may provide new insight regarding the pathophysiology of ALS and its clinical features. Recently developed technologies such as threshold tracking transcranial magnetic stimulation and automated nerve excitability tests have provided some clues about underlying pathophysiological processes linked to hyperexcitability. Additionally, these novel techniques have enabled clinicians to use the specific finding of hyperexcitability as a useful diagnostic biomarker, enabling clarification of various ALS-mimic syndromes, and the prediction of disease development in pre-symptomatic carriers of familial ALS. In terms of nerve excitability tests for peripheral nerves, an increase in persistent Na+ conductances has been identified as a major determinant of peripheral hyperexcitability in ALS, inversely correlated with the survival in ALS. As such, the present Review will focus primarily on the puzzling theory of hyperexcitability in ALS and summarize clinical and pathophysiological implications for current and future ALS research.

Neuroprotective Effects of Sacral Epidural Neuromodulation Following Spinal Cord Injury : An Experimental Study in Rats

OBJECTIVE: The purpose of this study is to evaluate neuroprotective effect of sacral neuromodulation in rat spinal cord injury (SCI) model in the histological and functional aspects. METHODS: Twenty-one female Sprague Dawley rats were randomly divided into 3 groups : the normal control group (CTL, n=7), the SCI with sham stimulation group (SCI, n=7), and the SCI with electrical stimulation (SCI+ES, n=7). Spinal cord was injured by dropping an impactor from 25 mm height. Sacral nerve electrical stimulation was performed by the following protocol : pulse duration, 0.1 ms; frequency, 20 Hz; stimulation time, 30 minutes; and stimulation duration, 4 weeks. Both locomotor function and histological examination were evaluated as scheduled. RESULTS: The number of anterior horn cell was 12.3+/-5.7 cells/high power field (HPF) in the CTL group, 7.8+/-4.9 cells/HPF in the SCI group, and 6.9+/-5.5 cells/HPF in the SCI+ES group, respectively. Both the SCI and the SCI+ES groups showed severe loss of anterior horn cells and myelin fibers compared with the CTL group. Cavitation and demyelinization of the nerve fibers has no significant difference between the SCI group and the SCI+ES group. Cavitation of dorsal column was more evident in only two rats of SCI group than the SCI+ES group. The locomotor function of all rats improved over time but there was no significant difference at any point in time between the SCI and the SCI+ES group. CONCLUSION: In a rat thoracic spinal cord contusion model, we observed that sacral neuromodulation did not prevent SCI-induced myelin loss and apoptosis.

The effects of electrical shock on the expressions of aquaporin subunits in the rat spinal cords / 대한해부학회지

We analyzed aquaporin (AQP) expression in the rat spinal cord following an electrical shock (ES) to elucidate the roles of AQP in spinal cord injury (SCI) induced by an electrical burn. In control animals, AQP1 immunoreactivity was observed in the small diameter dorsal horn fibers of laminae I and II and in astrocytes and neurons in the spinal cord. Both AQP4 and AQP9 immunoreactivity were detected in astrocytes. One week after the ES, AQP1 immunoreactivity in dorsal horn fibers was downregulated to 83, 61, and 33% of control levels following a 1-, 4-, or 6-second ES, respectively. However, AQP1 immunoreactivity in ventral horn neurons increased to 1.3-, 1.5-, and 2.4-fold of control levels following a 1-, 4-, or 6-second ES, respectively. AQP4 immunoreactivity was upregulated after an ES in laminae I and II astrocytes in a stimulus-intensity independent manner. Unlike AQP1 and AQP4, AQP9 immunoreactivity was unaffected by the ES. These findings indicate that altered AQP immunoreactivity may be involved in SCI following an ES.

Effect of endogenous brain derived neurotrophic factor on GAP-43 expression in the anterior horn of the spinal cord in rats with sciatic nerve injury / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of endogenous brain derived neurotrophic factor (BDNF) on GAP-43 expression in the anterior horn of the spinal cord in rats following sciatic nerve injury.</p><p><b>METHODS</b>BDNF antibody was injected intraperitoneally in rats with crushing injury of the sciatic nerve, and the control rats received normal saline only after sciatic nerve injury. At 7 and 14 days after the injection, the expression of GAP-43 in the anterior horn of the corresponding segments of the spinal cord was detected by Western blot and RT-PCR.</p><p><b>RESULTS</b>The expressions of GAP-43 protein and mRNA in the anterior horn of the spinal cord were significantly down-regulated in rats with BDNF antibody injection as compared with those in the control group (P<0.01).</p><p><b>CONCLUSION</b>Endogenous BDNF may regulate the expression of GAP-43 in the spinal cord anterior horn after sciatic nerve injury in rats.</p>

Aspectos neurobiológicos implicados en el miedo animal / Neurobiological aspects involved in animal fear

El miedo es una emoción que sirve para la expresión de comportamientos defensivos en situaciones de peligro. Posee un sustrato biológico, con base en el funcionamiento coordinado de los diferentes sistemas orgánicos. Particularmente, el sistema nervioso en su actividad intrínseca genera la vivencia y la acción motriz derivada. En efecto, se ha hallado la intervención de varias estructuras neuroanatómicas como la amígdala e hipotálamo, así como un gran conjunto de moléculas distintas como neurotransmisores y sus receptores. La interacción anatomofuncional causa la emoción. Al igual que se cuenta con la capacidad de producir el miedo, también se puede regular su generación. Para este mecanismo se encuentran determinadas estructuras neuroanatómicas como la corteza prefrontal y orbitofrontal, y sustancias como el GABA y los opiáceos, que inhiben o reducen la actividad en las zonas activas que actúan en el miedo. El equilibrio entre la activación y la inhibición posibilita la ocurrencia del miedo en las circunstancias requeridas y no de una manera descontextualizada o generalizada. En esta revisión se presenta una descripción de diferentes aspectos relevantes en la generación y regulación de la emoción.

Fear is an emotion that is useful for expressing defensive behaviors in dangerous situations. It has a biological support based on the coordinating functionality of different organic systems. Particularity, the nervous system in its intrinsic activity generates the experience and the derived motor action. In fact, researchers have discovered the participation of several neuroanatomical structures such as the amygdala and hypothalamus, as well as a wide range of molecules such as neurotransmitters and their receptors. The anatomical and physiological interactions cause emotion. Since the ability to produce fear exists, the nervous system may regulate it, too. Certain anatomical structures are found for this mechanism such as the prefrontal and orbitofrontal cortex and molecules like GABA and opiates, which inhibited or reduced the activity in the active zones that act upon fear. The balance between activation and inhibition enables the event of fear in the circumstances required and not in an out-of-context or generalized manner. This review presents a description of different relevant aspects in thegeneration and regulation of the emotion.

A Case of Type III Proximal Spinal Muscular Atrophy Distinguished from Distal Spinal Muscular Atrophy: A case report

Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by progressive anterior horn cell degeneration leading to motor weakness, muscular atrophy and denervation. Recently, the genes responsible for proximal muscular atrophy have been identified and named as survivor motor neuron (SMN) and neuronal apoptosis inhibitory protein genes. The clinical symptoms, courses and evaluation findings of proximal SMA type III are similar to those of distal SMA and proximal muscle myopathies such as limb gir-dle muscular dystrophy and fascioscapulohumeral muscular dystrophy. It cannot be diagnosed with muscle biopsy and electromyographic findings exclusively. In our case, the patient showed similar clinical manifestations of distal SMA. So we couldn't diagnose this case as SMA type III until we detected SMN 1 gene deletion. This case could be a good model for diagnostic approach to SMA type III and differential diagnosis to similar diseases.

Effect of intrathecal midazolam on the anterior horn cells of adult albino rat's spinal cord experimental and microscopical study

Midazolam, is the only clinically available water soluble beuzodiazepine, has an analgesic action by its effect on the benzodiazepine GABA receptors complex. It can be used as an adjuvant to potentiate the effect of local anesthetics when injected intrathecally to relieve chronic medronical low back pain, but its safety is still in need for more evaluation. In the present study, 21 adult Albino rats were used and divided into 3 equal groups. The first group was considered a control, while animals in the second group were injected with a single intrathecal dose of midazolam. Animals of the third group were injected with three successive doses of the same drug. The spinal cord at the level of the cervical region was dissected, paraffin sections were prepared at 6 urn thickness and stained by H. and E. stain, toluidin blue stain, Nauta and Gygax stain and methyl green pyronin stain. The results showed no changes in either cell diameter or nuclear diameter after single dose of intrathecal injection of the Midazolam. Also, no changes in nucleic acid contents were detected. Repeated intrathecal injections led to a decrease in the diameters of both the cell and its nuclei as well as nuclei/cytoplasmic ratio [N/C ratio]. The nucleic acid contents were still also not affected

Location of somatic sensory neurons of the skin and dorsal nerve of the penis in rabbits / 中华男科学杂志

<p><b>OBJECTIVE</b>To trace the segmental distribution of somatic sensory neurons of the skin and dorsal nerve in the rabbitś penis.</p><p><b>METHODS</b>The experiment was performed on 8 adult male rabbits with the nerve tracing method of retrograde axonal transport of horseradish peroxidase (HRP), which was injected into the dermis around the penis and the dorsal nerve of the penis. The rabbits were sacrificed five days later to harvest the spinal cord segments and the dorsal root ganglia of lumbosacral segments for histological study.</p><p><b>RESULTS</b>The HRP tracing showed that a number of labeled HRP positive neurons appeared in spinal ganglia (S2 - S4) in all the rabbits, and distributed segmentally. The counts of the positive neurons different segments were: S2 (215.0 +/- 10.2) , S3 (242.2 +/- 8.3) and S4 (109.7 +/- 8.4) respectively, with statistically significant difference between the two groups.</p><p><b>CONCLUSION</b>The rabbit's sensory nerve fibers in both the skin and the dorsal nerve of the penis are rooted in the S2-S4 segments of spinal ganglia, which distribute regularly.</p>

Morphological Changes of Anterior Horn Cells of Lumbar Spinal Cord after Anterior Root Avulsion in Adult Rat / 대한해부학회지

The morphological changes in the anterior horn of the L4 and L5 spinal segments were observed following anterior root avulsion in the adult male Sprague-Dawley rat (300~350 gm) at 5 days, 1 week, 2 weeks and 3 weeks postlesion. The animals were perfused with 4% paraformaldehyde, 0.15% picric acid in 0.1 M phosphate buffer solution and cryostat sections were prepared. Immunohistochemistry was used to identify changes of the phenotype in the anterior horn cells. Primary antibodies, goat anti-choline acetyltransferase (ChaT, 1 : 500, Chemicon), mouse antirat ED-1 (1 : 200, Serotec), rabbit anti-glial fibrillary acidic protein (GFAP, 1 : 200, DAKO) and rabbit anti-vascular endothelial growth factor (VEGF, 1 : 500, Santa Cruz Biotechnology) were used. Avidin-Biotin complex method was performed for immunohistochemical reaction and color reaction was developed with DAB-H2O2. Following results were observed in the anterior horn of lumbar spinal cord; 1. The number of ChaT-immunoreactive (ir) cells were reduced 20% level of control animals at 3 weeks after avulsion. 2. ED-1-ir microglia were significantly increased at 1 week and processes of ED-1-ir microglia surrounded around the axotomized neuronal cell bodies. 3. Gliosis defined by extensive GFAP immunoreactivity was observed both ipsilateral and contralateral side of lesion but the VEGF-ir cells were significantly increased in the ipsilateral side of lesion. Therefore, this study suggested that the majority of axotomized motor neurons were degenerated and the cellular proliferation and phenotype changes including glial cell activation were observed in the lumbar spinal cord after anterior root avulsion of adult rats.

Segmental Zoster Paresis Showing Spinal Nerve Roots Involvement on Gadolinium-Enhanced MRI

Segmental zoster paresis is a focal, asymmetric limb weakness caused by a herpes zoster infection. It is a rare complication of herpes zoster and the exact pathogenesis is uncertain. However, the most likely cause is the direct spread of the virus from the sensory ganglia to the anterior horn cells or anterior spinal nerve roots. We experienced two patients with segmental zoster paresis who showed both anterior and posterior root involvement on a gadolinium-enhanced MRI, supporting this hypothesis.

The primary observation of congenital clubfoot / 中华外科杂志

<p><b>OBJECTIVE</b>To explore the possible correlations between clinical and experimental pathological changes of congenital clubfoot and the pathodynamic developmental procedure.</p><p><b>METHODS</b>Eighty-three female Wistar rats were administered with retinoic acid on the 10th day after pregnancy. And from February 2001 to February 2004, 48 patients were analyzed with electropysiological examination.</p><p><b>RESULTS</b>There was clubfoot-like deformity in 53.7% of the experimental fetuses. Persistence of the embryonic position of the talus and tibia in fetuses was observed. Poor overlapping between talus and calcaneus was seen. Cell apoptosis at the anterior corner of spinal cord were seen. Of all the patients, 68.3% were abnormal with electropysiological examination. The pathological sites were frequently localized in lumbarsacral region.</p><p><b>CONCLUSION</b>Congenital clubfoot is correlated closely with defects of neural tube and spinal cord.</p>

The Effect of Ependymal Cell Transplantation on Nerve Regeneration after Spinal Cord Injury in Rats / 대한해부학회지

Nerve regeneration in the central nervous system has been studied by grafting various tissues and cells. Choroid plexus epithelial cells represent a continuation of ventricular ependymal cells and have the same origin as regarded as modified ependymal cells. To study the use of choroid plexus ependymal cell grafting for nerve regeneration in the spinal cord, the choroid plexus was excised from the lateral and fourth ventricles of adult Sprague-Dawley rats, minced into small fragments, and grafted at the T9 level in adult rat spinal cord transected or contused. In this study, transplants of choroid plexus ependymal cells were successfully used to promote functional and structural recovery after spinal cord transection and contusion. The area of damaged spinal cord was diminished after choroid plexus ependymal cells transplantation. Nearly normal anterior horn cells were observed immediately distal to the transected region. Tyrosine hydroxylase immunoreactive descending fibers were observed in the distal region beyond transected area. These findings indicate that choroid plexus ependymal cells have the ability to facilitate axonal growth, suggesting that they may be a promising candidate as graft for the promotion of nerve regeneration in the spinal cord.

Morphological Study of the Effects of Olfactory Bulb Transplants after Complete Spinal Cord Transection / 대한해부학회지

In the olfactory bulb, normal and transected olfactory axons are able to enter, regenerate, and reestablish lost synaptic contacts with their targets, throughout the lifetime of the organism. It was expected that studies of olfactory bulb ensheathing glia will provide important advances for the field of neural regeneration. Purpose of this study is to analyze morphologically the effects of olfactory bulb transplants into the cord after complete transection. Forty Sprague-Dawley rats were used in this study. Spinal cord of the rats were transected after laminectomy followed by insertion of chopped olfactory bulb tissues immediately and 3 weeks after the operation. In this study, transplants of olfactory bulb were successfully used to promote functional and structural recovery after complete spinal cord transection. The area of damaged spinal cord was greatly diminished after olfactory bulb transplantation. Nearly normal anterior horn cells were observed immediately distal to the transected region. Tyrosine hydroxylase immunoreactive descending fibers were observed in the distal region beyond transected area.

A Case of Exon 7 and 8 Deletion of Survival Motor Neuron Gene in Spinal Muscular Atrophy

Spinal muscular atrophy(SMA) is a genetic disorder of the motor neurons that cause muscular weakness and muscular atrophy due to anterior horn cell degeneration. Classic spinal muscular atrophy patient is caused by mutation in the chromosome 5(q11.2-q13.3), and the majority of the patient shows homozygous deletion of the telomeric survival motor neuron(SMN) gene in the chromosome 5. Deletion of exon 7 and 8 of the SMN gene and deletion of exon 4 and 5 of the neuronal apoptosis inhibitory protein(NAIP) are typically observed in SMA patients. The SMN protein plays a role in an essential cell metabolism process, the splicing of pre mRNA in the spliceosomes. We report a 7 month old male with SMA. He showed rapidly aggrdvatial muscular weakness and died at 7 months. His DNA analysis proved deletion of exon 7 and 8 of the telomeric copy of the SMN gene.