The effect of continuous epidural electrical stimulation on neuronal proliferation in cerebral ischemic rats.

OBJECTIVE: To investigate the effect of electrical stimulation (ES) on the recovery of motor skill and neuronal cell proliferation. METHODS: The male Sprague-Dawley rats were implanted with an epidural electrode over the peri-ischemic area after photothrombotic stroke in the dominant sensorimotor cortex. All rats were randomly assigned into the ES group and control group. The behavioral test of a single pellet reaching task (SPRT) and neurological examinations including the Schabitz's photothrombotic neurological score and the Menzies test were conducted for 2 weeks. After 14 days, coronal sections were obtained and immunostained for neuronal cell differentiation markers including bromodeoxyuridine (BrdU), neuron-specific nuclear protein (NeuN), and doublecortin (DCX). RESULTS: On the SPRT, the motor function in paralytic forelimbs of the ES group was significantly improved. There were no significant differences in neurological examinations and neuronal cell differentiation markers except for the significantly increased number of DCX+ cells in the corpus callosum of the ES group (p<0.05). But in the ES group, the number of NeuN+ cells in the ischemic cortex and the number of NeuN+ cells and DCX+ cells in the ischemic striatum tended to increase. In the ES group, NeuN+ cells in the ischemic hemisphere and DCX+ cells and BrdU+ cells in the opposite hemisphere tended to increase compared to those in the contralateral. CONCLUSION: The continuous epidural ES of the ischemic sensorimotor cortex induced a significant improvement in the motor function and tended to increase neural cell proliferation in the ischemic hemisphere and the neural regeneration in the opposite hemisphere.

Extreme elongation of the transverse processes of the fifth lumbar vertebra: an unusual variant.

The fifth lumbar vertebra has massive transverse processes that are continuous with the pedicle and encroach the body of the vertebra. These processes are mainly meant for the attachment of the iliolumbar ligament. With increasing age, the iliolumbar ligament can undergo secondary degenerative changes such as calcification, hyalinization, and myxoid degeneration. The authors present the incidental discovery of extremely elongated transverse processes of the fifth lumbar vertebra in a 45-year-old woman who underwent surgery for an intervertebral disc herniation. We also propose a possible pathogenesis to explain this rare condition and conclude that this unusual variant may be caused by calcification of the iliolumbar ligament rather than a congenital anomaly.

A case of occipital neuralgia in the greater and lesser occipital nerves treated with neurectomy by using transcranial Doppler sonography: technical aspects.

Occipital neuralgia is usually defined as paroxysmal stabbing pain in the greater or lesser occipital nerve (GON or LON) distribution. In occipital neuralgia patients, surgical considerations are carefully taken into account if medical management is ineffective. However, identification of the occipital artery by palpation in patients with thick necks or small occipital arteries can be technically difficult. Therefore, we established a new technique using transcranial Doppler (TCD) sonography for more accurate and rapid identification. The patient was a 64-year-old man who had undergone C1-C3 screw fixation and presented with intractable stabbing pain in the bilateral GON and LON distributions. In cases in which pain management was performed using medication, physical therapy, nerve block, or radiofrequency thermocoagulation, substantial pain relief was not consistently achieved, and recurrence of pain was reported. Therefore, we performed occipital neurectomy of the bilateral GON and LON by using TCD sonography, which helped detect the greater occipital artery easily. After the operation, the patient's headache disappeared gradually, although he had discontinued all medication except antidepressants. We believe that this new technique of occipital neurectomy via a small skin incision performed using TCD sonography is easy and reliable, has a short operative time, and provides rapid pain relief.

Dual extradural cortical stimulation in chronic stroke patients with large infarcts: technical case report.

OBJECTIVE AND IMPORTANCE: Recent works on extradural cortical stimulation have been successful in improving neurological recovery in chronic stroke patients. On the other hand, single perirolandic stimulations are often associated with disappointing results. CLINICAL PRESENTATION: We report two cases of chronic stroke in which the magnitude of infarct was too large to be improved with single perirolandic stimulation. Patient 1 had severe hemiplegia associated with large cortical infarct in the right frontoparietal area. The patient could neither stand independently or walk. Patient 2 had hemiplegia and aphasia due to cortical infarct in the left middle cerebral artery territory. Both patients had intensive rehabilitative training for more than 6 months with no beneficial results. INTERVENTION: Two paddle electrodes covering frontal and parietal area were implanted, followed by dual cortical stimulation with concurrent rehabilitative training in patient 1. After 6 months of stimulation, the patient could walk with a good posture. Two paddle electrodes were implanted to cover pre-motor and motor cortex in patient 2. After similar treatment, the motor function was markedly improved. CONCLUSION: Dual cortex stimulation, which acts on more diffuse areas or functionally related areas, is beneficial to promote the motor recovery in chronic stroke patients with large infarcts.

Both compensation and recovery of skilled reaching following small photothrombotic stroke to motor cortex in the rat.

Large lesions produced by stroke to the forelimb region of motor cortex of the rat feature post-stroke improvement that in the main is due to compensation. The present study describes both recovery and compensation of forelimb use in a reach-to-eat (skilled reaching) task following small photothrombotic stroke. The rats were pretrained before stroke, and then assessed using endpoint measures and biometric movement analysis during rehabilitation in the acute and chronic post-stroke periods. Histological and MRI analysis indicated that the stroke consisted of a small lesion surrounded by cortex featuring scattered cell loss, likely of the large pyramidal cells that characterize the forelimb region of motor cortex. The stroke reduced reaching success, especially on the most demanding measure of success on first reach attempts, in the acute period, but with rehabilitation, performance returned to pre-stroke levels. Reach movements as assessed by biometric measures were severely impaired acutely but displayed significant recovery chronically although this recovery was not complete. The results suggest that not only do rats show post-stroke compensation in skilled reaching but they can also display functional recovery. It is suggested that recovery is mediated by the spared neurons in the peri-infarct region of forelimb motor cortex. The results demonstrate the utility of a small lesion model for studying post-stroke neural and behavioral change and support the view that optimal post-stroke treatment should be directed toward limiting tissue loss.

Effect of prolonged cortical stimulation differs with size of infarct after sensorimotor cortical lesions in rats.

Motor deficit improvement is limited in rats with a large sensorimotor cortex infarct, even with cortical stimulation during rehabilitation. However, we find prolonged stimulation that differs with the size of cortical lesion to be effective. Two weeks of prolonged epidural electrical stimulation and rehabilitative training were delivered to rats whose cortex had been subjected to photothrombotic infarct after training in a single-pellet reaching task. Continuous stimulation greatly improved recovery in animals with large infarcts (6 mm diameter), while intermittent stimulation was more effective in animals with small (4 mm) lesions. Thus, prolonged cortical stimulation is a strategy to enhance motor recovery in photothrombotic infarct model rats. However, pattern and duration of stimulation requires modification depending on the extent of infarct.

Sasim attenuates LPS-induced TNF-alpha production through the induction of HO-1 in THP-1 differentiated macrophage-like cells.

AIM OF THE STUDY: Sasim, a traditional prescription composed of seven herbal mixtures, has been widely used as an oriental medicine for the treatment of cerebral infarction in Korea. However, the regulatory mechanisms by which the formula affects immune processing in cerebral infarction patients remain unknown. MATERIALS AND METHODS: The levels of secretory protein of tumor necrosis factor (TNF)-alpha were determined in both THP-1 differentiated macrophage-like (THP-1/M) cells and Peripheral blood mononuclear cells (PBMCs) from cerebral infarction patients. Also, the levels of protein and mRNA of TNF-alpha and heme oxygenase-1 (HO-1) were detected in THP-1/M cells under our experimental condition. RESULTS: Sasim markedly suppressed lipopolysaccharide (LPS)-induced TNF-alpha at the levels of secretory protein and mRNA in both PBMCs from cerebral infarction patients and THP-1/M cells. Interestingly, Sasim strongly induced HO-1, the rate-limiting enzyme of heme catabolism, at both the protein and mRNA levels in THP-1/M cells. Treatment with tin protoporphyrin IX (SnPP), an inhibitor of the catalytic activity of HO, significantly abolished the suppressive effect of Sasim on LPS-induced TNF-a production in THP-1/M cells. CONCLUSIONS: These data indicate that Sasim may be beneficial in the cessation of inflammatory processes associated with cerebral infarction through the induction of HO-1 expression.

Unipolar and continuous cortical stimulation to enhance motor and language deficit in patients with chronic stroke: report of 2 cases.

BACKGROUND: Stroke often leads to permanent neurological deficit despite extensive therapeutic and rehabilitative efforts; and in chronic stages, it is difficult to restore neurological function. Recently, bipolar and intermittent cortical stimulation combined with rehabilitation has been reported to be effective in chronic hemiparetic stroke. However, optimal parameters of cortical stimulation for chronic stroke have not been determined to restore neurological function in chronic stages of stroke. CASE DESCRIPTIONS: We report 2 cases of chronic stroke whose neurological functions were improved by continuous, unipolar cortical stimulation combined with rehabilitation. Patient 1 presented motor and language deficit associated with cortical infarct in the left middle cerebral artery territory, which occurred 18 months before admission. Patient 2 presented motor deficit associated with subcortical infarct in the internal capsule 8 months before admission. Unipolar electrodes were implanted epidurally to cover the contralateral premotor and motor cortex in both cases, and an additional electrode was implanted over the Broca area in patient 1. Follow-up evaluation after 4 months of stimulation and concurrent rehabilitation showed improvement of Fugl-Meyer and FIM scores in both patients, and of speech and articulation in patient 1, whose electrode covered the Broca area. No adverse effects were observed during the period of treatment. CONCLUSION: Unipolar and continuous cortical stimulation with rehabilitation is beneficial for improving neurological deficit in selected cases of chronic stroke.

Spontaneous epidural hematoma recurred three times.

Spontaneous spinal epidural hematoma (SSEH) is a rare space-occupying disease. The pathogenesis of SSEH is unclear, but anticoagulant therapy, arteriovenous malformation, coagulopathy, tumors and infection are risk factors. Ventral SSEH is even more rare, as the ventral sac is fixed firmly to the posterior longitudinal ligament. The authors report a very rare case, a 16-year-old previously healthy female who had repeated relapse of cervico-thoracic SSEH. This occurred three times in the ventral epidural space with subsequent syringomyelia, without structural abnormality and coagulopathy. The patient underwent conservative care twice, and two operations. The diagnosis was made by magnetic resonance imaging. In rapidly progressing SSEH, the clinician should make the diagnosis as early as possible to enable spinal decompression surgery.

Samul extract protects against the H2O2-induced apoptosis of H9c2 cardiomyoblasts via activation of extracellular regulated kinases (Erk) 1/2.

Samul extract, containing Radix Rehmanniae, Radix Angelicae Gigantis, Radix Paeoniae, and Rhizoma Cnidii, has been traditionally used for treatment of ischemic heart and brain damages in Oriental medicine. However, little is known about the mechanism by which Samul rescues cells from cytotoxic damage. This study was designed to investigate the protective mechanisms of Samul on H(2)O(2)-induced death of H9c2 cells. Treatment with H(2)O(2) markedly decreased the viability of H9c2 cells in a dose- and time-dependent manner, which was significantly prevented by pre-treatment with Samul. The nature of death of H9c2 cells by H(2)O(2) was demonstrated by apoptotic features, including ladder-pattern fragmentation of genomic DNA and chromatin condensation, which were markedly abolished by pretreatment of Samul in H(2)O(2)-treated cells. We further demonstrated that MEK inhibitor, PD98059, dose-dependently attenuated the protective effects of Samul against H(2)O(2), whereas inhibitors of Jnk and p38 did not. Consistently, Samul induced the early phosphorylation of Erk, p44, in H(2)O(2)-treated cells. In addition, treatment with Samul also resulted in an increase of expression of anti-apotogenic Bcl2 protein, which was decreased by H(2)O(2). However, it inhibited the expression of apotogenic Bax protein in H(2)O(2)-treated cells. Taken together, these results suggest that the protective effects of Samul against oxidative damage may be achieved via activation of MAP kinase, Erk as well as Bcl2 family proteins.

Effect of Acanthopanax senticosus on lipoprotein lipase in 3T3-L1 adipocytes.

The effect of Acanthopanax senticosus (AS) leaves on lipoprotein lipase (LPL) was investigated in 3T3-L1 adipocytes. A water extract of AS leaves increased the LPL activity in culture medium of adipocytes in a dose- and time-dependent manner. The AS extract contained heparin-like LPL releasing components, however, the increase of medium LPL activity was continued up until 12 h, in contrast to the rapid decline after heparin treatment. The increase of LPL mRNA was also observed after AS extract treatment, suggesting that LPL induction occurs at the transcriptional level. The AS extract could partially reverse the LPL suppression by tumour necrosis factor-alpha in 3T3-L1 adipocytes. These results of an AS extract-induced increase of LPL activity in vitro suggest the possible action of AS as a facilitator of plasma triglyceride clearance.