Stroke research in non-human primates (NHPs) with gyrencephalic brains is a critical step in overcoming the translational barrier that limits the development of new pharmaceutical and rehabilitative strategies for stroke. White-matter stroke (WMS) has a unique pathophysiology from graymatter stroke and is not well understood because of a lack of pertinent animal models. To create a precise capsular infarct model in the cynomolgus macaque, we first used electrical stimulation to map hand movements, followed by viral tracing of the hand motor fibers (hMFs). This enabled us to identify stereotactic targets in the posterior limb of the internal capsule (PLIC). Neural tracing showed that hMFs occupy the full width of the PLIC, owing to overlap with the motor fibers for the leg. Furthermore, the hMFs were distributed in an oblique shape, requiring coronal tilting of the target probe. We used the photothrombotic infarct lesioning technique to precisely destroy the hMFs within the internal capsule. Double-point infarct lesioning that fully compromised the hMFs resulted in persistent hand motor and walking deficits whereas single-point lesioning did not. Minor deviations in targeting failed to produce persistent motor deficits. Accurate stereotactic targeting with thorough involvement of motor fibers is critical for the production of a capsular infarct model with persistent motor deficits. In conclusion, the precision capsular infarct model can be translated to the NHP system to show persistent motor deficits and may be useful to investigate the mechanism of post-stroke recovery as well as to develop new therapeutic strategies for the WMS.

The brain grows with age in non-human primates (NHPs). Therefore, atlas-based stereotactic coordinates cannot be used directly to target subcortical structures if the size of the animal's brain differs from that used in the stereotactic atlas. Furthermore, growth is non-uniform across different cortical regions, making it difficult to simply apply a single brain-expansion ratio. We determined the skull reference lines that best reflect changes in brain size along the X, Y, and Z axes and plotted the changes in reference-line length against the changes in body weight. The skull reference lines had a linear relationship with body weight. However, comparison of skull reference lines with body weight confirmed the non-uniform skull growth during postnatal development, with skull growth more prominent in the X and Y axes than the Z axis. Comparing the differences between the atlas-based lengths and those calculated empirically from plot-based linear fits, we created craniometric indices that can be used to modify stereotactic coordinates along all axes. We verified the accuracy of the corrected stereotactic targeting by infusing dye into internal capsule in euthanized and preserved NHP brains. Our axis-specific, craniometric-index-adjusted stereotactic targeting enabled us to correct for targeting errors arising from differences in brain size. Histological verification showed that the method was accurate to within 1 mm. Craniometric index-adjusted targeting is a simple and relatively accurate method that can be used for NHP stereotactic surgery in the general laboratory, without the need for high-resolution imaging.
Body Weight ; Brain ; Internal Capsule ; Methods ; Primates ; Skull

OBJECTIVE: Necrotizing pneumonia (NP) is a severe complication of lobar pneumonia caused by various pathogens. The immunopathogenesis and clinical characteristics of NP in children are not clearly understood. We wanted to evaluate the clinical characteristics and suggest in part the immunopathogenesis of NP. METHODS: We reviewed retrospectively the medical charts and radiographic materials of eight patients with NP, who were diagnosed by chest radiography and chest computed tomography at the Department of Pediatrics, Soonchunhyang University Hospitals at Cheonan and Bucheon from January 2002 to December 2011. RESULTS: They were previously healthy, 2.1 to 4.6 years of ages (mean, 2.8+/-1.0 years) and three boys and five girls. All of them had pleural effusion. Five patients had pneumonic consolidations in right upper lung field. Three patients had pneumatocele. They developed leukocytosis (mean, 19,400+/-6,400/mm3), higher C-reactive protein level (mean, 25.1+/-8.0 mg/dL). The etiologic agents were revealed in two patients; Streptococcus pneumonia (S. pneumonia) was revealed in one patient and S. pneumonia and Mycoplasma pneumonia in the other patient. Three patients were treated with additional intravenous immunoglobulin. Clinical improvement was prolonged: fever lasted 10 to 23 days, and length of hospitalization was 15 to 36 days. NP or pneumatocele were completely resolved on the follow-up radiographic studies in all of the patients. CONCLUSION: Although the previously healthy young children with NP had protracted clinical course, they recovered without any problematic sequelae. Our results suggest that the immunopathogenesis of NP in children may be associated with the exaggerated immune reaction of the host to insults from initial bacterial infections, rather than the pathogen-induced cytopathies.
Bacterial Infections ; C-Reactive Protein ; Child* ; Chungcheongnam-do ; Female ; Fever ; Follow-Up Studies ; Gyeonggi-do ; Hospitalization ; Hospitals, University ; Humans ; Immunoglobulins ; Leukocytosis ; Lung ; Pediatrics ; Pleural Effusion ; Pneumonia* ; Pneumonia, Mycoplasma ; Radiography ; Retrospective Studies ; Streptococcus ; Thorax

We investigated the migration of endogenous neural stem cells (NSCs) toward an infarct lesion in a photo-thrombotic stroke model. The lesions produced by using rose bengal dye (20 mg/kg) with cold light in the motor cortex of Sprague-Dawley rats were also evaluated with sequential magnetic resonance imaging (MRI) from 30 minutes through 8 weeks. Migration of NSCs was identified by immunohistochemistry for nestin monoclonal antibody in the lesion cortex, subventricular zone (SVZ), and corpus callosum (CC). The contrast to noncontrast ratio (CNR) on MRI was greatest at 12 hours in DWI and decreased over time. By contrast, T1-weighted and T2-weighted images showed a constant CNR from the beginning through 8 weeks. MRI of the lesional cortex correlated with histopathologic findings, which could be divided into three stages: acute (edema and necrosis) within 24 hours, subacute (acute and chronic inflammatory cell infiltration) at 2 to 7 days, and chronic (gliofibrosis) at 2 to 4 weeks. The volume of the infarct was significantly reduced by reparative gliofibrosis. The number of nestin+ NSCs in the contralateral SVZ was similar to that of the ipsilateral SVZ in each group. However, the number of nestin+ NSCs in the ipsilateral cortex and CC increased at 12 hours to 3 days compared with the contralateral side (p<0.01) and was reduced significantly by 7 days (p<0.01). Active emigration of internal NSCs from the SVZ toward the infarct lesion may also contribute to decreased volume of the infarct lesion, but the self-repair mechanism by endogenous NSCs is insufficient to treat stroke causing extensive neuronal death. Further studies should be focused on amplification technologies of NSCs to enhance the collection of endogenous or transplanted NSCs for the treatment of stroke.
Cold Temperature ; Corpus Callosum ; Emigration and Immigration ; Immunohistochemistry ; Intermediate Filament Proteins ; Light ; Magnetic Resonance Imaging ; Models, Theoretical ; Motor Cortex ; Nerve Tissue Proteins ; Neural Stem Cells ; Neurons ; Rats, Sprague-Dawley ; Rose Bengal ; Stem Cells ; Stroke ; Transplants

OBJECTIVE: To assess the accuracy and confidence of the glenohumeral joint injection using an anterior approach in cadavers. METHOD: Eight shoulders from six cadavers were placed supine with arm abduction and external rotation. A single physiatrist performed all the ultrasonography guided injection using an anterior approach. A twenty-one gauge needle was placed into shoulder and intraarticular position was verified by small injection of blue dye. And then the anatomic dissection was done. RESULTS: Seven out of eight (87.5%) were judged to be accurately placed by the anatomic section. In one case, the needle tip was placed in supraglenoid space. In one of the seven accurate cases, the needle traversed the long head tendon of biceps muscle. Confidence of the injections was 87.5%. CONCLUSION: Ultrasonography guided glenohumeral injection using an anterior approach was efficient and safe.
Arm ; Cadaver ; Head ; Injections, Intra-Articular ; Muscles ; Needles ; Shoulder ; Shoulder Joint ; Tendons

OBJECTIVE: To investigate and quantify functional deficit in ischemic stroke rat. METHOD: Male Sprague-Dawley rats were divided into sham group and stroke group. Permanent cerebral ischemia was inflicted on the stroke group by occluding the middle cerebral artery (MCAO). The proportion of hind limb weight bearing pressure was also measured. The withdrawal threshold values in the hindpaws were measured by using von-Frey hair for seven days from the day before ischemia. RESULTS: The proportion of paretic hind limb pressure to whole hind limb pressure in stroke group was significantly reduced than sham group (p<0.05). The withdrawal threshold values of the paretic hindpaw in stroke group were not different from those in the sham group during whole experimental session (p>0.05). Garcia motor score of stroke group was reduced significantly than sham group in whole experimental session after MCAO (p<0.05). The proportions of right hind limb pressure showed no correlation with Garcia motor score after MCAO (p>0.05). CONCLUSION: Ischemic stroke in rats can lead to the reduction of pressure at paretic hind limb. The motor test for pressure weight borne on the paretic leg may provide functional information in the future studies with ischemic stroke rat.
Animals ; Brain Ischemia ; Extremities ; Hair ; Humans ; Infarction, Middle Cerebral Artery ; Leg ; Male ; Middle Cerebral Artery ; Rats ; Rats, Sprague-Dawley ; Salicylamides ; Stroke ; Weight-Bearing

OBJECTIVE: To determine optimal stimulation site for median motor conduction study, we compared fixed distance (7 cm proximal to the recording electrode) stimulation method and distal wrist crease stimulation method. METHOD: Nerve conduction studies were performed in 65 hands of 36 healthy adults without neurologic abnormality. Median motor responses were recorded from abductor pollicis brevis (APB) with the stimulations at the point 7 cm proximal to the recording electrode and at the distal wrist crease. The distal latencies and onset-to-peak amplitudes were measured and compared between two techniques. The distal latencies were also compared to that of ulnar compound muscle action potential (CMAP) obtained with fixed distance stimulation (7 cm proximal to the recording electrode). And we measured median nerve actual length from distal wrist crease to APB muscle motor point by anatomic dissection of 12 hands. RESULTS: The distal latencies of median CMAP to APB with 7 cm fixed distance stimulation and distal wrist crease stimulation were 2.91+/-0.37 ms and, 2.75+/-0.41 ms respectively. The differences were statistically significant. The distal latency of ulnar CMAP was 2.50+/-0.32 ms. Differences in distal latencies between ulnar CMAPs and not only 7 cm fixed distance median stimulation but also distal wrist crease median stimulation were also statistically significant. The mean length of median nerve from distal wrist crease to APB motor point was 5.91+/-0.77 cm. CONCLUSION: We suggest that the median motor nerve conduction study using distal wrist crease stimulation was an easier and more rapid procedure than fixed distance median motor nerve conduction study.
Action Potentials ; Adult ; Electrodes ; Hand ; Humans ; Median Nerve ; Muscles ; Neural Conduction ; Wrist

OBJECTIVES: Balloon cells and dysplastic neurons are histopathological hallmarks of the cortical tubers of tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) of the Taylor type. They are believed to be the epileptogenic substrate and cause therapeutic drug resistant epilepsy in man. P-glycoprotein (P-gp) is the product of multidrug resistance gene (MDR1), and it maintains intracellular drug concentration at a relatively low level. The authors investigated expression of P-gp in balloon cells and dysplastic neurons of cortical tubers in patients with TSC. METHODS: An immunohistochemical study using the primary antibody for P-gp, as an indicative of drug resistance, was performed in the cortical tuber tissues in two patients of surgical resection for epilepsy and six autopsy cases. RESULTS: Balloon cells of each lesion showed different intensity and number in P-gp immunopositivity. P-gp immunopositivity in balloon cells were 28.2%, and dysplastic neurons were 22.7%. These immunoreactivities were more prominent in balloon cells distributed in the subpial region than deeper region of the cortical tubers. Capillary endothelial cells within the cortical tubers also showed P-gp immunopositivity. CONCLUSION: In this study, the drug resistance protein P-glycoprotein in balloon cells and dysplastic neurons might explain medically refractory epilepsy in TSC.
Autopsy ; Drug Resistance* ; Drug Resistance, Multiple ; Endothelial Cells ; Epilepsy ; Genes, MDR ; Humans ; Malformations of Cortical Development ; Neurons ; P-Glycoprotein ; Tuberous Sclerosis* ; Up-Regulation*

Neuropathic arthropathy is a chronic and progressive disease of bone and joints. One of the most common causes of neuropathic arthropathy is syringomyelia. Syringomyelia associated with Arnold-Chiari I malformation has been well documented in many reports. We report a case of 76 year-old woman presented with the right elbow joint pain and stiffness. Her symptom was caused by neuropathic arthropathy associated with Arnold-Chiari I malformation and syringomyelia. The purpose of this paper is to emphasize that neuropathic arthropathy requires the evaluation of central nervous system to assess for occult causal lesion.
Aged ; Central Nervous System ; Elbow Joint ; Female ; Humans ; Joints ; Syringomyelia*

OBJECTIVE: A prospective, randomized, controlled clinical study is performed to verify the effectiveness of epidural dexamethasone-soaked gelatin sponges to reduce postoperative pain following lumbar microdiscectomy. METHODS: Twenty-three patients (10 men and 13 women) undergoing lumbar microdiscectomy were included. Five pieces of gelatin sponge measuring 1 x 1 cm (Gelfoam; Pharmacia & Upjohn, Kalamazoo, MI, USA), soaked with either 5mg dexamethasone or an equal amount (2 mL) of saline, were left on the decompressed nerve root after unilateral hemilaminectomy, flavectomy and discectomy. RESULTS: Subjective visual analog scale(VAS) scores of leg pain in the dexamethasone group on the first, third and fifth postoperative days (2.5, 2.5, 1.7, respectively) were significantly lower than in the control group (5.0, 4.8, 3.6) ( P<0.05). No side effects related to the dexamethasone-soaked gelatin sponges were observed. CONCLUSION: The intraoperative application of dexamethasone-soaked gelatin sponges during lumbar microdiscectomy can provide effective postoperative analgesia without complications.
Analgesia ; Dexamethasone ; Diskectomy ; Gelatin* ; Humans ; Leg ; Male ; Pain, Postoperative ; Porifera* ; Prospective Studies